The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No.: 111651 (SPNG-001) Title: A study to evaluate GSK Biologicals candidate formulations of pneumococcal vaccines in young adults. Rationale: The aim of this study was to evaluate the safety and immunogenicity of different formulations of GlaxoSmithKline (GSK) Biologicals investigational pneumococcal vaccines containing Streptococcus pneumoniae proteins alone or in combination with the 10-valent conjugate vaccines in comparison to Pneumovax 23, in a healthy young adult population. Pneumococcal investigational vaccine (PV): GSK Biologicals investigational pneumococcal vaccine. Pneumovax 23 TM vaccine: MSD Sanofi Pasteur 23-valent polysaccharide pneumococcal vaccine (23PPV) Phase: I Study Period: 30 June 2008 to 15 January 2009 Study Design: Observer-blind, randomized and controlled study with 7 parallel groups. Centres: 1 centre in Belgium. Indication: Pneumococcal vaccine in young adult subjects aged between 18 years old and 40 years old, in good general health. Treatment: The study groups were as follows: PV1 : subjects receiving PV formulation 1 PV2 : subjects receiving PV formulation 2 PV3 : subjects receiving PV formulation 3 PV4 : subjects receiving PV formulation 4 PV5 : subjects receiving PV formulation 5 PV6 : subjects receiving PV formulation 6 23PPV : subjects receiving 23PPV All vaccines were administered by intramuscular injection into the deltoid region of the non-dominant arm. Objectives: To evaluate the safety profile of the investigational pneumococcal vaccines when administered intramuscularly in healthy adults as a single dose at Day 0 and again at 2 months (Day 0 and Day 60). Primary Outcome/Efficacy Variable: Safety Occurrence of any vaccine related and grade 3 solicited local and general symptoms during a 7-day follow up period (i.e. day of vaccination and 6 subsequent days) after each vaccine dose. Occurrence of any vaccine related and grade 3 unsolicited adverse events (AEs) during a 31-day follow up period (i.e. day of vaccination and 30 subsequent days) after each vaccine dose. Occurrence of any vaccine related serious adverse events (SAE) occurring from Day 0 to study conclusion (Day 90). Occurrence of any grade 3 haematological, biochemical, or urinary abnormalities, at 1 and 7 days after each vaccine dose.
Secondary Outcome/Efficacy Variables: Safety Occurrence of any solicited local and general symptoms during a 7-day follow up period (i.e. day of vaccination and 6 subsequent days) after each vaccine dose. Occurrence of any unsolicited AEs during a 31-day follow up period (i.e. day of vaccination and 30 subsequent days) after each vaccine dose. Occurrence of any haematological, biochemical, or urinary abnormalities at 1 and 7 days after each vaccine dose. Immunogenicity Anti-pneumococcal and anti-non typable Haemophilus influenzae (anti-nthi) investigational vaccine antigens at Days 0, 30 and 90. Criteria for assessment: - Anti-pneumolysin toxoid (Anti-dPly), anti-pneumococcal histidine triad protein D (anti-phtd) and anti-protein D (anti-pd) antibody concentrations (measured by ELISA or Multiplex assays), prior to first vaccination and 30 days (1 month) after each vaccination. -Anti-Polysaccharide (anti-ps) opsonophagocytic activity (OPA) titres, prior to first vaccination and 30 days (1 month) after each vaccination. Statistical Methods: The analyses were performed on the Total Vaccinated cohort and the ATP (According to Protocol) cohort for immunogenicity. - The Total Vaccinated cohort included all subjects with at least one study vaccine administration documented. - The ATP cohort for immunogenicity included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures defined in the protocol, with no elimination criteria during the study) for whom pre and post vaccination results were available for at least one assay. Analysis of Immunogenicity: The analysis of immunogenicity was performed on the ATP cohort for immunogenicity. Antibody geometric mean concentrations or titres (GMCs or GMTs) and seropositivity rates were calculated with their 95% confidence Intervals (CIs) for each treatment group, each time point and each antibody assessed. Analysis of safety: The analysis of safety was performed on the Total Vaccinated cohort. The percentage of subjects with each individual solicited local and general symptoms within the 7-day (Days 0-6) follow-up period after vaccination was summarized with its exact 95% CIs for each group per dose and across doses. The same tabulation was performed for grade 3 symptoms and for general symptoms assessed by the investigators as causally related to vaccination. All solicited local symptoms were assessed as causally related to the study vaccination. The percentage of subjects with unsolicited AEs within the 31-day (Days 0-30) follow-up period after vaccination were tabulated according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred term. The same tabulation was performed for grade 3 AEs and for AEs assessed by the investigators as having a causal relationship to vaccination. The occurrence of SAEs and that of SAEs assessed by the investigators as causally related to study vaccination reported during the study period (from Day 0 to Day 90) were tabulated according to the MedDRA preferred term. For each haematology, biochemistry and urine parameter, the grading was summarized per study group, at 1 and 7 days after each vaccine dose. Study Population: Healthy male or female between the ages of 18-40 years at the time of first vaccination. If the subject was female of child-bearing potential, she had to agree to use adequate contraception and not become pregnant for the duration of the study. Written informed consent was obtained from all the subjects before enrolment in the study. Number of subjects PV1 PV2 PV3 PV4 PV5 PV6 23PPV Planned, N 12 24 24 24 24 24 24 Randomized, N (Total Vaccinated cohort) 12 24 24 24 24 24 24 Completed, n (%) 10 (83.3) 21 (87.5) 23 (95.8) 24 (100) 24 (100) 21 (87.5) 23 (95.8) Total Number Subjects Withdrawn, 2 (16.7) 3 (12.5) 1 (4.2) 0 (0.0) 0 (0.0) 3 (12.5) 1 (4.2) n (%) Withdrawn due to Adverse Events, 0 (0.0) 2 (8.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
n (%) Withdrawn due to Lack of Efficacy, Not Not Not Not Not Not Not n (%) applicable applicable applicable applicable applicable applicable applicable Withdrawn for other reasons, n (%) 2 (16.7) 1 (4.2) 1 (4.2) 0 (0.0) 0 (0.0) 3 (12.5) 1 (4.2) Demographics PV1 PV2 PV3 PV4 PV5 PV6 23PPV N (Total Vaccinated cohort) 12 24 24 24 24 24 24 Females : Males 4:8 14:10 16:8 14:10 14:10 15:9 15:9 Mean Age, years (SD) 26.3 (5.74) 25.8 (5.39) 26.3 (5.17) 23.3 (3.87) 25.0 (6.53) 23.0 (5.09) 26.3 (6.90) White - Caucasian / European heritage, n (%) 11 (91.7) 24 (100) 24 (100) 24 (100) 24 (100) 24 (100) 24 (100) Primary Efficacy Results: Number (%) of subjects reporting solicited local symptoms reported during the 7-day (Days 0-6) post-vaccination period following each dose and across doses (Total Vaccinated cohort) PV1 PV2 PV3 95 % CI 95 % CI 95 % CI Symptom Intensity N n % LL UL N n % LL UL N n % LL UL Dose 1 Pain Any 12 5 41.7 15.2 72.3 24 16 66.7 44.7 84.4 24 21 87.5 67.6 97.3 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Redness Any 12 1 8.3 0.2 38.5 24 3 12.5 2.7 32.4 24 1 4.2 0.1 21.1 > 50 mm* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Swelling Any 12 0 0.0 0.0 26.5 24 1 4.2 0.1 21.1 24 1 4.2 0.1 21.1 > 50 mm* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Dose 2 Pain Any 10 8 80.0 44.4 97.5 21 15 71.4 47.8 88.7 23 19 82.6 61.2 95.0 Grade 3* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Redness Any 10 0 0.0 0.0 30.8 21 4 19.0 5.4 41.9 23 4 17.4 5.0 38.8 > 50 mm* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Swelling Any 10 1 10.0 0.3 44.5 21 3 14.3 3.0 36.3 23 3 13.0 2.8 33.6 > 50 mm* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Across Doses Pain Any 12 10 83.3 51.6 97.9 24 20 83.3 62.6 95.3 24 24 100 85.8 100 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Redness Any 12 1 8.3 0.2 38.5 24 7 29.2 12.6 51.1 24 5 20.8 7.1 42.2 > 50 mm* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Swelling Any 12 1 8.3 0.2 38.5 24 4 16.7 4.7 37.4 24 4 16.7 4.7 37.4 > 50 mm* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 PV4 PV5 PV6 95 % CI 95 % CI 95 % CI Symptom Intensity N n % LL UL N n % LL UL N n % LL UL Dose 1 Pain Any 24 19 79.2 57.8 92.9 24 24 100 85.8 100 24 23 95.8 78.9 99.9 Grade 3* 24 2 8.3 1.0 27.0 24 0 0.0 0.0 14.2 24 3 12.5 2.7 32.4 Redness Any 24 6 25.0 9.8 46.7 24 9 37.5 18.8 59.4 24 11 45.8 25.6 67.2 > 50 mm* 24 1 4.2 0.1 21.1 24 3 12.5 2.7 32.4 24 1 4.2 0.1 21.1 Swelling Any 24 4 16.7 4.7 37.4 24 10 41.7 22.1 63.4 24 11 45.8 25.6 67.2 > 50 mm* 24 1 4.2 0.1 21.1 24 2 8.3 1.0 27.0 24 1 4.2 0.1 21.1 Dose 2 Pain Any 24 22 91.7 73.0 99.0 24 21 87.5 67.6 97.3 21 20 95.2 76.2 99.9 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 21 1 4.8 0.1 23.8 Redness Any 24 7 29.2 12.6 51.1 24 9 37.5 18.8 59.4 21 4 19.0 5.4 41.9
> 50 mm* 24 0 0.0 0.0 14.2 24 1 4.2 0.1 21.1 21 1 4.8 0.1 23.8 Swelling Any 24 5 20.8 7.1 42.2 24 8 33.3 15.6 55.3 21 8 38.1 18.1 61.6 > 50 mm* 24 0 0.0 0.0 14.2 24 1 4.2 0.1 21.1 21 0 0.0 0.0 16.1 Across Doses Pain Any 24 23 95.8 78.9 99.9 24 24 100 85.8 100 24 24 100 85.8 100 Grade 3* 24 2 8.3 1.0 27.0 24 0 0.0 0.0 14.2 24 4 16.7 4.7 37.4 Redness Any 24 8 33.3 15.6 55.3 24 11 45.8 25.6 67.2 24 13 54.2 32.8 74.4 > 50 mm* 24 1 4.2 0.1 21.1 24 4 16.7 4.7 37.4 24 2 8.3 1.0 27.0 Swelling Any 24 7 29.2 12.6 51.1 24 11 45.8 25.6 67.2 24 14 58.3 36.6 77.9 > 50 mm* 24 1 4.2 0.1 21.1 24 3 12.5 2.7 32.4 24 1 4.2 0.1 21.1 23PPV 95 % CI Symptom Intensity N n % LL UL Dose 1 Pain Any 24 22 91.7 73.0 99.0 Grade 3* 24 1 4.2 0.1 21.1 Redness Any 24 5 20.8 7.1 42.2 > 50 mm* 24 1 4.2 0.1 21.1 Swelling Any 24 5 20.8 7.1 42.2 > 50 mm* 24 1 4.2 0.1 21.1 Dose 2 Pain Any 23 1 4.3 0.1 21.9 Grade 3* 23 0 0.0 0.0 14.8 Redness Any 23 1 4.3 0.1 21.9 > 50 mm* 23 0 0.0 0.0 14.8 Swelling Any 23 0 0.0 0.0 14.8 > 50 mm* 23 0 0.0 0.0 14.8 Across Doses Pain Any 24 22 91.7 73.0 99.0 Grade 3* 24 1 4.2 0.1 21.1 Redness Any 24 5 20.8 7.1 42.2 > 50 mm* 24 1 4.2 0.1 21.1 Swelling Any 24 5 20.8 7.1 42.2 > 50 mm* 24 1 4.2 0.1 21.1 N = number of subjects with at least one documented dose n (%) = number(percentage) of subjects reporting at least once the symptom 95% CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any local symptom regardless of intensity grade Grade 3 pain = pain that prevented normal activity *Primary outcome variable Primary Efficacy Results: Number (%) of subjects reporting solicited general symptoms reported during the 7-day (Days 0-6) post-vaccination period following each dose and across doses (Total Vaccinated cohort) PV1 PV2 PV3 95 % CI 95 % CI 95 % CI Symptom Intensity/ Relationship N n % LL UL N n % LL UL N n % LL UL Dose 1 Fatigue Any 12 2 16.7 2.1 48.4 24 4 16.7 4.7 37.4 24 6 25.0 9.8 46.7 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 1 8.3 0.2 38.5 24 4 16.7 4.7 37.4 24 4 16.7 4.7 37.4 Gastrointestinal Any 12 1 8.3 0.2 38.5 24 3 12.5 2.7 32.4 24 7 29.2 12.6 51.1 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2
Related* 12 1 8.3 0.2 38.5 24 2 8.3 1.0 27.0 24 4 16.7 4.7 37.4 Headache Any 12 4 33.3 9.9 65.1 24 6 25.0 9.8 46.7 24 13 54.2 32.8 74.4 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 1 4.2 0.1 21.1 Related* 12 3 25.0 5.5 57.2 24 5 20.8 7.1 42.2 24 7 29.2 12.6 51.1 Malaise Any 12 1 8.3 0.2 38.5 24 2 8.3 1.0 27.0 24 5 20.8 7.1 42.2 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 1 8.3 0.2 38.5 24 2 8.3 1.0 27.0 24 3 12.5 2.7 32.4 Myalgia Any 12 6 50.0 21.1 78.9 24 0 0.0 0.0 14.2 24 3 12.5 2.7 32.4 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 6 50.0 21.1 78.9 24 0 0.0 0.0 14.2 24 1 4.2 0.1 21.1 Temperature (Orally) 37.5 C 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 2 8.3 1.0 27.0 > 39.5 C* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 2 8.3 1.0 27.0 Dose 2 Fatigue Any 10 2 20.0 2.5 55.6 21 2 9.5 1.2 30.4 23 4 17.4 5.0 38.8 Grade 3* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Related* 10 1 10.0 0.3 44.5 21 2 9.5 1.2 30.4 23 4 17.4 5.0 38.8 Gastrointestinal Any 10 0 0.0 0.0 30.8 21 1 4.8 0.1 23.8 23 1 4.3 0.1 21.9 Grade 3* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 1 4.3 0.1 21.9 Related* 10 0 0.0 0.0 30.8 21 1 4.8 0.1 23.8 23 1 4.3 0.1 21.9 Headache Any 10 3 30.0 6.7 65.2 21 2 9.5 1.2 30.4 23 7 30.4 13.2 52.9 Grade 3* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Related* 10 1 10.0 0.3 44.5 21 1 4.8 0.1 23.8 23 3 13.0 2.8 33.6 Malaise Any 10 1 10.0 0.3 44.5 21 0 0.0 0.0 16.1 23 1 4.3 0.1 21.9 Grade 3* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Related* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 1 4.3 0.1 21.9 Myalgia Any 10 1 10.0 0.3 44.5 21 2 9.5 1.2 30.4 23 2 8.7 1.1 28.0 Grade 3* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Related* 10 0 0.0 0.0 30.8 21 2 9.5 1.2 30.4 23 2 8.7 1.1 28.0 Temperature (Orally) 37.5 C 10 1 10.0 0.3 44.5 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 >39.5 C* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Related* 10 0 0.0 0.0 30.8 21 0 0.0 0.0 16.1 23 0 0.0 0.0 14.8 Across Doses Fatigue Any 12 3 25.0 5.5 57.2 24 4 16.7 4.7 37.4 24 8 33.3 15.6 55.3 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 1 8.3 0.2 38.5 24 4 16.7 4.7 37.4 24 6 25.0 9.8 46.7 Gastrointestinal Any 12 1 8.3 0.2 38.5 24 4 16.7 4.7 37.4 24 7 29.2 12.6 51.1 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 1 4.2 0.1 21.1 Related* 12 1 8.3 0.2 38.5 24 3 12.5 2.7 32.4 24 5 20.8 7.1 42.2 Headache Any 12 5 41.7 15.2 72.3 24 7 29.2 12.6 51.1 24 15 62.5 40.6 81.2 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 1 4.2 0.1 21.1 Related* 12 3 25.0 5.5 57.2 24 6 25.0 9.8 46.7 24 9 37.5 18.8 59.4 Malaise Any 12 1 8.3 0.2 38.5 24 2 8.3 1.0 27.0 24 5 20.8 7.1 42.2 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 1 8.3 0.2 38.5 24 2 8.3 1.0 27.0 24 4 16.7 4.7 37.4 Myalgia Any 12 6 50.0 21.1 78.9 24 2 8.3 1.0 27.0 24 5 20.8 7.1 42.2 Grade 3* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 6 50.0 21.1 78.9 24 2 8.3 1.0 27.0 24 3 12.5 2.7 32.4 Temperature (Orally) Symptom 37.5 C 12 1 8.3 0.2 38.5 24 0 0.0 0.0 14.2 24 2 8.3 1.0 27.0 >39.5 C* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 12 0 0.0 0.0 26.5 24 0 0.0 0.0 14.2 24 2 8.3 1.0 27.0 PV4 PV5 PV6 95 % CI 95 % CI 95 % CI Intensity/ Relationship N n % LL UL N n % LL UL N n % LL UL
Dose 1 Fatigue Any 24 9 37.5 18.8 59.4 24 5 20.8 7.1 42.2 24 14 58.3 36.6 77.9 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 7 29.2 12.6 51.1 24 3 12.5 2.7 32.4 24 12 50.0 29.1 70.9 Gastrointestinal Any 24 3 12.5 2.7 32.4 24 2 8.3 1.0 27.0 24 3 12.5 2.7 32.4 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 3 12.5 2.7 32.4 24 1 4.2 0.1 21.1 24 2 8.3 1.0 27.0 Headache Any 24 10 41.7 22.1 63.4 24 7 29.2 12.6 51.1 24 7 29.2 12.6 51.1 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 7 29.2 12.6 51.1 24 5 20.8 7.1 42.2 24 4 16.7 4.7 37.4 Malaise Any 24 7 29.2 12.6 51.1 24 3 12.5 2.7 32.4 24 4 16.7 4.7 37.4 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 5 20.8 7.1 42.2 24 3 12.5 2.7 32.4 24 4 16.7 4.7 37.4 Myalgia Any 24 1 4.2 0.1 21.1 24 2 8.3 1.0 27.0 24 6 25.0 9.8 46.7 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 1 4.2 0.1 21.1 24 2 8.3 1.0 27.0 24 5 20.8 7.1 42.2 Temperature (Orally) 37.5 C 24 2 8.3 1.0 27.0 24 1 4.2 0.1 21.1 24 2 8.3 1.0 27.0 >39.5 C* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 2 8.3 1.0 27.0 24 0 0.0 0.0 14.2 24 2 8.3 1.0 27.0 Dose 2 Fatigue Any 24 12 50.0 29.1 70.9 24 7 29.2 12.6 51.1 21 12 57.1 34.0 78.2 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 21 0 0.0 0.0 16.1 Related* 24 10 41.7 22.1 63.4 24 5 20.8 7.1 42.2 21 10 47.6 25.7 70.2 Gastrointestinal Any 24 1 4.2 0.1 21.1 24 1 4.2 0.1 21.1 21 3 14.3 3.0 36.3 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 21 0 0.0 0.0 16.1 Related* 24 1 4.2 0.1 21.1 24 1 4.2 0.1 21.1 21 2 9.5 1.2 30.4 Headache Any 24 8 33.3 15.6 55.3 24 5 20.8 7.1 42.2 21 10 47.6 25.7 70.2 Grade 3* 24 1 4.2 0.1 21.1 24 0 0.0 0.0 14.2 21 0 0.0 0.0 16.1 Related* 24 7 29.2 12.6 51.1 24 5 20.8 7.1 42.2 21 8 38.1 18.1 61.6 Malaise Any 24 5 20.8 7.1 42.2 24 0 0.0 0.0 14.2 21 3 14.3 3.0 36.3 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 21 1 4.8 0.1 23.8 Related* 24 5 20.8 7.1 42.2 24 0 0.0 0.0 14.2 21 3 14.3 3.0 36.3 Myalgia Any 24 2 8.3 1.0 27.0 24 1 4.2 0.1 21.1 21 5 23.8 8.2 47.2 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 21 0 0.0 0.0 16.1 Related* 24 2 8.3 1.0 27.0 24 0 0.0 0.0 14.2 21 5 23.8 8.2 47.2 Temperature (Orally) 37.5 C 24 0 0.0 0.0 14.2 24 2 8.3 1.0 27.0 21 1 4.8 0.1 23.8 >39.5 C* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 21 0 0.0 0.0 16.1 Related* 24 0 0.0 0.0 14.2 24 2 8.3 1.0 27.0 21 1 4.8 0.1 23.8 Across Doses Fatigue Any 24 14 58.3 36.6 77.9 24 9 37.5 18.8 59.4 24 18 75.0 53.3 90.2 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 13 54.2 32.8 74.4 24 6 25.0 9.8 46.7 24 15 62.5 40.6 81.2 Gastrointestinal Any 24 4 16.7 4.7 37.4 24 3 12.5 2.7 32.4 24 5 20.8 7.1 42.2 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 4 16.7 4.7 37.4 24 2 8.3 1.0 27.0 24 3 12.5 2.7 32.4 Headache Any 24 14 58.3 36.6 77.9 24 10 41.7 22.1 63.4 24 14 58.3 36.6 77.9 Grade 3* 24 1 4.2 0.1 21.1 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 11 45.8 25.6 67.2 24 8 33.3 15.6 55.3 24 10 41.7 22.1 63.4 Malaise Any 24 10 41.7 22.1 63.4 24 3 12.5 2.7 32.4 24 7 29.2 12.6 51.1 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 1 4.2 0.1 21.1 Related* 24 8 33.3 15.6 55.3 24 3 12.5 2.7 32.4 24 7 29.2 12.6 51.1 Myalgia Any 24 3 12.5 2.7 32.4 24 3 12.5 2.7 32.4 24 9 37.5 18.8 59.4 Grade 3* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 Related* 24 3 12.5 2.7 32.4 24 2 8.3 1.0 27.0 24 9 37.5 18.8 59.4 Temperature/(Or ally) 37.5 C 24 2 8.3 1.0 27.0 24 3 12.5 2.7 32.4 24 3 12.5 2.7 32.4 >39.5 C* 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2 24 0 0.0 0.0 14.2
Related* 24 2 8.3 1.0 27.0 24 2 8.3 1.0 27.0 24 3 12.5 2.7 32.4 23PPV 95 % CI Symptom Intensity/Relationship N n % LL UL Dose 1 Fatigue Any 24 6 25.0 9.8 46.7 Grade 3* 24 1 4.2 0.1 21.1 Related* 24 5 20.8 7.1 42.2 Gastrointestinal Any 24 1 4.2 0.1 21.1 Grade 3* 24 0 0.0 0.0 14.2 Related 24 1 4.2 0.1 21.1 Headache Any 24 1 4.2 0.1 21.1 Grade 3* 24 0 0.0 0.0 14.2 Related* 24 1 4.2 0.1 21.1 Malaise Any 24 2 8.3 1.0 27.0 Grade 3* 24 0 0.0 0.0 14.2 Related* 24 1 4.2 0.1 21.1 Myalgia Any 24 2 8.3 1.0 27.0 Grade 3* 24 0 0.0 0.0 14.2 Related* 24 2 8.3 1.0 27.0 Temperature/(Orally) 37.5 C 24 1 4.2 0.1 21.1 >39.5 C* 24 0 0.0 0.0 14.2 Related* 24 1 4.2 0.1 21.1 Dose 2 Fatigue Any 23 2 8.7 1.1 28.0 Grade 3* 23 0 0.0 0.0 14.8 Related* 23 2 8.7 1.1 28.0 Gastrointestinal Any 23 1 4.3 0.1 21.9 Grade 3* 23 0 0.0 0.0 14.8 Related* 23 0 0.0 0.0 14.8 Headache Any 23 3 13.0 2.8 33.6 Grade 3* 23 0 0.0 0.0 14.8 Related* 23 3 13.0 2.8 33.6 Malaise Any 23 0 0.0 0.0 14.8 Grade 3* 23 0 0.0 0.0 14.8 Related* 23 0 0.0 0.0 14.8 Myalgia Any 23 0 0.0 0.0 14.8 Grade 3* 23 0 0.0 0.0 14.8 Related* 23 0 0.0 0.0 14.8 Temperature/(Orally) 37.5 C 23 0 0.0 0.0 14.8 >39.5 C* 23 0 0.0 0.0 14.8 Related* 23 0 0.0 0.0 14.8 Across Doses Fatigue Any 24 7 29.2 12.6 51.1 Grade 3* 24 1 4.2 0.1 21.1 Related* 24 6 25.0 9.8 46.7 Gastrointestinal Any 24 2 8.3 1.0 27.0 Grade 3* 24 0 0.0 0.0 14.2 Related* 24 1 4.2 0.1 21.1 Headache Any 24 4 16.7 4.7 37.4 Grade 3** 24 0 0.0 0.0 14.2 Related* 24 4 16.7 4.7 37.4 Malaise All 24 2 8.3 1.0 27.0 Grade 3* 24 0 0.0 0.0 14.2 Related* 24 1 4.2 0.1 21.1 Myalgia Any 24 2 8.3 1.0 27.0
Grade 3* 24 0 0.0 0.0 14.2 Related* 24 2 8.3 1.0 27.0 Temperature/(Orally) 37.5 C 24 1 4.2 0.1 21.1 >39.5 C* 24 0 0.0 0.0 14.2 Related* 24 1 4.2 0.1 21.1 N= number of subjects with at least one documented dose n (%)= number(percentage) of subjects reporting at least once the symptom 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any general symptom regardless of the intensity grade or relationship to vaccination Grade 3 = symptoms that prevented normal activity Related = general symptoms assessed by the investigator to be casually related to the study vaccination *Primary outcome variable Primary Efficacy Results: Number (%) of subjects with haematology and biochemistry abnormalities during the postvaccination period (Total Vaccinated cohort) Grade 1 Grade 2 Grade 3* Grade 4 Laboratory test Timing N n % n % n % n % Alanine Aminotransferase PV1 Day 1 12 2 16.7 0 0.0 0 0.0 0 0.0 Day 7 12 2 16.7 0 0.0 0 0.0 0 0.0 Day 61 10 1 10.0 0 0.0 0 0.0 0 0.0 PV2 Day 1 24 3 12.5 0 0.0 0 0.0 0 0.0 Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 21 2 9.5 0 0.0 0 0.0 0 0.0 Day 67 21 1 4.8 0 0.0 0 0.0 0 0.0 PV3 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 61 23 2 8.7 0 0.0 0 0.0 0 0.0 Day 67 23 2 8.7 0 0.0 0 0.0 0 0.0 PV4 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 67 24 1 4.2 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 24 1 4.2 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Aspartate aminotransferse PV1 Day 1 12 2 16.7 0 0.0 0 0.0 0 0.0 Day 7 12 1 8.3 0 0.0 0 0.0 0 0.0 Day 61 10 1 10.0 0 0.0 0 0.0 0 0.0 PV2 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 67 21 1 4.8 0 0.0 0 0.0 0 0.0 PV4 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 61 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 67 24 1 4.2 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 2 8.3 0 0.0 0 0.0 0 0.0 Cholesterol PV1 Day 1 12 2 16.7 2 16.7 1 8.3 0 0.0 Day 7 12 2 16.7 2 16.7 1 8.3 0 0.0 Day 61 10 3 30.0 2 20.0 1 10.0 0 0.0 Day 67 10 2 20.0 2 20.0 2 20.0 0 0.0 PV2 Day 1 24 3 12.5 2 8.3 1 4.2 0 0.0 Day 7 24 3 12.5 3 12.5 1 4.2 0 0.0 Day 61 21 3 14.3 2 9.5 0 0.0 0 0.0 PV3 Day 1 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 7 24 3 12.5 1 4.2 0 0.0 0 0.0 Day 61 23 4 17.4 2 8.7 0 0.0 0 0.0 Day 67 23 3 13.0 2 8.7 0 0.0 0 0.0 PV4 Day 1 24 4 16.7 1 4.2 0 0.0 0 0.0 Day 7 24 5 20.8 1 4.2 0 0.0 0 0.0 Day 61 24 4 16.7 3 12.5 0 0.0 0 0.0 Day 67 24 4 16.7 3 12.5 1 4.2 0 0.0
PV5 Day 1 24 3 12.5 1 4.2 0 0.0 0 0.0 Day 7 24 3 12.5 1 4.2 0 0.0 0 0.0 Day 61 24 7 29.2 2 8.3 1 4.2 0 0.0 Day 67 24 6 25.0 4 16.7 1 4.2 0 0.0 PV6 Day 1 24 2 8.3 1 4.2 1 4.2 0 0.0 Day 7 24 1 4.2 1 4.2 1 4.2 0 0.0 Day 61 21 2 9.5 1 4.8 0 0.0 0 0.0 Day 67 21 4 19.0 1 4.8 0 0.0 0 0.0 23PPV Day 1 24 3 12.5 2 8.3 1 4.2 0 0.0 Day 7 24 5 20.8 3 12.5 0 0.0 0 0.0 Day 61 22 3 13.6 2 9.1 1 4.5 0 0.0 Day 67 23 4 17.4 4 17.4 2 8.7 0 0.0 Creatine Phosphokinase PV1 Day 1 12 1 8.3 1 8.3 0 0.0 0 0.0 Day 7 12 1 8.3 1 8.3 0 0.0 0 0.0 Day 61 10 1 10.0 0 0.0 0 0.0 0 0.0 Day 67 10 3 30.0 0 0.0 0 0.0 0 0.0 PV2 Day 1 24 3 12.5 1 4.2 0 0.0 0 0.0 Day 7 24 2 8.3 1 4.2 0 0.0 0 0.0 Day 61 21 3 14.3 1 4.8 0 0.0 0 0.0 Day 67 21 2 9.5 1 4.8 0 0.0 0 0.0 PV3 Day 1 24 2 8.3 2 8.3 0 0.0 0 0.0 Day 7 24 4 16.7 4 16.7 0 0.0 0 0.0 Day 61 23 2 8.7 2 8.7 0 0.0 0 0.0 Day 67 23 1 4.3 0 0.0 0 0.0 0 0.0 PV4 Day 1 24 4 16.7 2 8.3 0 0.0 0 0.0 Day 7 24 5 20.8 1 4.2 1 4.2 0 0.0 Day 61 24 2 8.3 1 4.2 0 0.0 0 0.0 Day 67 24 2 8.3 2 8.3 1 4.2 0 0.0 PV5 Day 1 24 2 8.3 1 4.2 0 0.0 0 0.0 Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 24 2 8.3 1 4.2 0 0.0 0 0.0 Day 67 24 3 12.5 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 4 16.7 3 12.5 2 8.3 0 0.0 Day 7 24 6 25.0 2 8.3 0 0.0 0 0.0 Day 61 21 3 14.3 0 0.0 0 0.0 0 0.0 23PPV Day 1 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 22 2 9.1 1 4.5 0 0.0 0 0.0 Day 67 23 1 4.3 0 0.0 0 0.0 0 0.0 Eosinophils PV3 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 PV5 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 PV6 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Haemoglobin PV1 Day 1 12 1 8.3 0 0.0 0 0.0 0 0.0 Day 7 12 1 8.3 0 0.0 0 0.0 0 0.0 Day 61 10 1 10.0 0 0.0 0 0.0 0 0.0 PV2 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 67 21 1 4.8 0 0.0 0 0.0 0 0.0 PV3 Day 1 24 1 4.2 1 4.2 1 4.2 0 0.0 Day 7 24 1 4.2 1 4.2 1 4.2 0 0.0 Day 61 23 1 4.3 1 4.3 1 4.3 0 0.0 Day 67 23 1 4.3 1 4.3 1 4.3 0 0.0 PV4 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 67 24 3 12.5 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0
Day 61 24 1 4.2 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 61 21 2 9.5 0 0.0 0 0.0 0 0.0 Day 67 21 3 14.3 0 0.0 0 0.0 0 0.0 23PPV Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 7 24 3 12.5 0 0.0 0 0.0 0 0.0 Day 61 22 3 13.6 0 0.0 0 0.0 0 0.0 Day 67 23 2 8.7 0 0.0 0 0.0 0 0.0 Haemoglobin decrease PV1 Day 1 12 7 58.3 0 0.0 0 0.0 0 0.0 Day 7 12 7 58.3 0 0.0 0 0.0 0 0.0 Day 61 10 8 80.0 0 0.0 0 0.0 0 0.0 Day 67 10 6 60.0 0 0.0 0 0.0 0 0.0 PV2 Day 1 24 14 58.3 0 0.0 0 0.0 0 0.0 Day 7 24 15 62.5 0 0.0 0 0.0 0 0.0 Day 61 21 10 47.6 0 0.0 0 0.0 0 0.0 Day 67 21 12 57.1 0 0.0 0 0.0 0 0.0 PV3 Day 1 24 11 45.8 0 0.0 0 0.0 0 0.0 Day 7 24 12 50.0 0 0.0 0 0.0 0 0.0 Day 61 23 11 47.8 0 0.0 0 0.0 0 0.0 Day 67 23 12 52.2 0 0.0 0 0.0 0 0.0 PV4 Day 1 24 14 58.3 0 0.0 0 0.0 0 0.0 Day 7 24 16 66.7 0 0.0 0 0.0 0 0.0 Day 61 24 15 62.5 0 0.0 0 0.0 0 0.0 Day 67 24 14 58.3 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 14 58.3 0 0.0 0 0.0 0 0.0 Day 7 24 16 66.7 0 0.0 0 0.0 0 0.0 Day 61 24 11 45.8 0 0.0 0 0.0 0 0.0 Day 67 24 14 58.3 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 14 58.3 0 0.0 0 0.0 0 0.0 Day 7 24 16 66.7 0 0.0 0 0.0 0 0.0 Day 61 21 13 61.9 1 4.8 0 0.0 0 0.0 Day 67 21 15 71.4 0 0.0 0 0.0 0 0.0 23PPV Day 1 24 12 50.0 0 0.0 0 0.0 0 0.0 Day 7 24 13 54.2 1 4.2 0 0.0 0 0.0 Day 61 22 8 36.4 1 4.5 0 0.0 0 0.0 Day 67 23 12 52.2 1 4.3 0 0.0 0 0.0 Lactate dehydrogenase PV3 Day 61 23 1 4.3 0 0.0 0 0.0 0 0.0 PV4 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 61 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 67 24 1 4.2 0 0.0 0 0.0 0 0.0 PV5 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 61 24 1 4.2 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 67 21 1 4.8 0 0.0 0 0.0 0 0.0 Lymphocytes PV4 Day 61 24 1 4.2 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 1 4.2 1 4.2 0 0.0 0 0.0 Day 61 24 1 4.2 1 4.2 1 4.2 0 0.0 PV6 Day 61 21 1 4.8 1 4.8 0 0.0 0 0.0 Neutrophils PV1 Day 1 12 3 25.0 3 25.0 0 0.0 0 0.0 Day 7 12 3 25.0 2 16.7 0 0.0 0 0.0 Day 61 10 2 20.0 1 10.0 0 0.0 0 0.0 Day 67 10 1 10.0 1 10.0 0 0.0 0 0.0 PV2 Day 1 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 7 24 3 12.5 0 0.0 0 0.0 0 0.0
Day 67 21 2 9.5 0 0.0 0 0.0 0 0.0 PV3 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 7 24 3 12.5 0 0.0 0 0.0 0 0.0 Day 67 23 2 8.7 1 4.3 0 0.0 0 0.0 PV4 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 7 24 3 12.5 0 0.0 0 0.0 0 0.0 Day 67 24 1 4.2 0 0.0 0 0.0 0 0.0 PV5 Day 7 24 1 4.2 1 4.2 0 0.0 0 0.0 Day 67 24 2 8.3 1 4.2 0 0.0 0 0.0 23PPV Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 22 1 4.5 0 0.0 0 0.0 0 0.0 Day 67 23 2 8.7 0 0.0 0 0.0 0 0.0 Platelets PV1 Day 1 12 1 8.3 1 8.3 1 8.3 0 0.0 Day 7 12 1 8.3 1 8.3 0 0.0 0 0.0 Day 61 10 1 10.0 1 10.0 1 10.0 0 0.0 Day 67 10 1 10.0 1 10.0 0 0.0 0 0.0 PV3 Day 7 24 1 4.2 1 4.2 1 4.2 0 0.0 Red blood cells (urine) PV1 Day 1 12 6 50.0 1 8.3 0 0.0 0 0.0 Day 7 12 2 16.7 0 0.0 0 0.0 0 0.0 Day 61 10 4 40.0 0 0.0 0 0.0 0 0.0 Day 67 10 3 30.0 2 20.0 0 0.0 0 0.0 PV2 Day 1 24 8 33.3 4 16.7 1 4.2 0 0.0 Day 7 24 9 37.5 4 16.7 1 4.2 0 0.0 Day 61 21 11 52.4 3 14.3 0 0.0 0 0.0 Day 67 21 14 66.7 6 28.6 0 0.0 0 0.0 PV3 Day 1 24 12 50.0 2 8.3 0 0.0 0 0.0 Day 7 24 12 50.0 6 25.0 1 4.2 0 0.0 Day 61 23 14 60.9 7 30.4 2 8.7 0 0.0 Day 67 23 11 47.8 7 30.4 1 4.3 0 0.0 PV4 Day 1 24 11 45.8 3 12.5 0 0.0 0 0.0 Day 7 24 8 33.3 4 16.7 1 4.2 0 0.0 Day 61 24 11 45.8 8 33.3 1 4.2 0 0.0 Day 67 24 13 54.2 7 29.2 2 8.3 0 0.0 PV5 Day 1 24 6 25.0 1 4.2 0 0.0 0 0.0 Day 7 24 6 25.0 4 16.7 0 0.0 0 0.0 Day 61 24 16 66.7 7 29.2 1 4.2 0 0.0 Day 67 24 10 41.7 6 25.0 1 4.2 0 0.0 PV6 Day 1 24 15 62.5 7 29.2 0 0.0 0 0.0 Day 7 24 9 37.5 4 16.7 0 0.0 0 0.0 Day 61 21 12 57.1 7 33.3 1 4.8 0 0.0 Day 67 21 13 61.9 8 38.1 0 0.0 0 0.0 23PPV Day 1 24 7 29.2 3 12.5 2 8.3 0 0.0 Day 7 24 12 50.0 6 25.0 1 4.2 0 0.0 Day 61 23 13 56.5 6 26.1 1 4.3 0 0.0 Day 67 23 9 39.1 6 26.1 1 4.3 0 0.0 Reticulocyte count PV1 Day 67 10 1 10.0 0 0.0 0 0.0 0 0.0 PV3 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 61 23 1 4.3 0 0.0 0 0.0 0 0.0 Day 67 23 1 4.3 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 White blood cells decrease PV1 Day 1 12 2 16.7 0 0.0 0 0.0 0 0.0 Day 7 12 2 16.7 0 0.0 0 0.0 0 0.0 Day 61 10 2 20.0 0 0.0 0 0.0 0 0.0 Day 67 10 1 10.0 0 0.0 0 0.0 0 0.0 PV2 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 PV3 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0
Day 67 23 1 4.3 0 0.0 0 0.0 0 0.0 PV5 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 23PPV Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 White blood cells increase PV2 Day 61 21 1 4.8 0 0.0 0 0.0 0 0.0 Day 67 21 1 4.8 0 0.0 0 0.0 0 0.0 PV3 Day 1 24 1 4.2 0 0.0 0 0.0 0 0.0 Day 61 23 1 4.3 0 0.0 0 0.0 0 0.0 PV4 Day 61 24 1 4.2 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 61 24 4 16.7 1 4.2 0 0.0 0 0.0 PV6 Day 1 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 61 21 2 9.5 0 0.0 0 0.0 0 0.0 23PPV Day 1 24 3 12.5 0 0.0 0 0.0 0 0.0 Day 7 24 1 4.2 0 0.0 0 0.0 0 0.0 Overall parameters PV1 Day 1 12 10 83.3 4 33.3 2 16.7 0 0.0 Day 7 12 10 83.3 4 33.3 1 8.3 0 0.0 Day 61 10 10 100.0 3 30.0 2 20.0 0 0.0 Day 67 10 8 80.0 5 50.0 2 20.0 0 0.0 PV2 Day 1 24 22 91.7 7 29.2 2 8.3 0 0.0 Day 7 24 20 83.3 6 25.0 2 8.3 0 0.0 Day 61 21 18 85.7 5 23.8 0 0.0 0 0.0 Day 67 21 16 76.2 7 33.3 0 0.0 0 0.0 PV3 Day 1 24 21 87.5 4 16.7 1 4.2 0 0.0 Day 7 24 21 87.5 11 45.8 3 12.5 0 0.0 Day 61 23 20 87.0 12 52.2 3 13.0 0 0.0 Day 67 23 18 78.3 10 43.5 2 8.7 0 0.0 PV4 Day 1 24 21 87.5 6 25.0 0 0.0 0 0.0 Day 7 24 23 95.8 5 20.8 2 8.3 0 0.0 Day 61 24 22 91.7 9 37.5 1 4.2 0 0.0 Day 67 24 21 87.5 9 37.5 4 16.7 0 0.0 PV5 Day 1 24 19 79.2 4 16.7 0 0.0 0 0.0 Day 7 24 20 83.3 6 25.0 0 0.0 0 0.0 Day 61 24 24 100.0 10 41.7 2 8.3 0 0.0 Day 67 24 21 87.5 9 37.5 2 8.3 0 0.0 PV6 Day 1 24 21 87.5 10 41.7 3 12.5 0 0.0 Day 7 24 22 91.7 7 29.2 1 4.2 0 0.0 Day 61 21 19 90.5 10 47.6 1 4.8 0 0.0 Day 67 21 18 85.7 8 38.1 0 0.0 0 0.0 23PPV Day 1 24 19 79.2 5 20.8 3 12.5 0 0.0 Day 7 24 21 87.5 9 37.5 1 4.2 0 0.0 Day 61 23 18 78.3 8 34.8 2 8.7 0 0.0 Day 67 23 17 73.9 10 43.5 3 13.0 0 0.0 N = number of subjects with laboratory results at the specified time point n(%) = number (percentage) of subjects with a maximum grade in the given category FDA Toxicity Grading Scale for biochemical parameters: Liver Function Tests-ALT, AST increase by factor Mild (Grade 1) Moderate (Grade 2) Severe (Grade 3) Potentially Life Threatening (Grade 4)** 1.1-2.5 x ULN 2.6-5.0 x ULN 5.1-10 x ULN > 10 x ULN Cholesterol 201-210 211-225 >226 - Creatinine mg/dl 1.5-1.7 1.8-2.0 2.1-2.5 >2.5 or requires dialysis Eosinophilscell/mm 3 650-1500 1501-5000 >5000 Hypereosinophilic
Hemoglobin 11.0-12.0 9.5-10.9 8.0-9.4 <8.0 (Female)-gm/dL Hemoglobin Any decrease - 1.5 1.6-2.0 2.1-5.0 >5.0 (Female) change from baseline valuegm/dl Hemoglobin (Male)- 12.5-13.5 10.5-12.4 8.5-10.4 <8.5 gm/dl Hemoglobin (Male) Any decrease - 1.5 1.6-2.0 2.1-5.0 >5.0 change from baseline valuegm/dl Lymphocytes 750-1,000 500-749 250-499 <250 Decrease-cell/mm 3 Neutrophils 1,500-2,000 1,000-1,499 500-999 <500 Decrease-cell/mm 3 Platelets Decreasecell/mm 125,000-140,000 100,000-124,000 25,000-99,000 <25,000 3 WBC Increasecell/mm 10,800-15,000 15,001-20,000 20,001-25,000 >25,000 3 WBC Decreasecell/mm 2,500-3,500 1,500-2,499 1,000-1,499 <1,000 3 ULN = upper limit normal Grades for study required tests not included within the FDA Toxicity Grading Scale: Normal Grade 1 Grade 2 Grade 3 Grade 4 (SAE) LDH 0-220 Units/L 1-1.5 x ULN 1.5-2 x ULN 2-3 x ULN >3 x ULN Reticulocytes 0.8-2.5 1-1.5 x ULN 1.5-2 x ULN 2-3 x ULN >3 x ULN index- Male Reticulocytes index- Female 0.8-4.1 1-1.5 x ULN 1.5-2 x ULN 2-3 x ULN >3 x ULN ULN = upper limit normal *Primary outcome variable Primary Efficacy Results: Number (%) of subjects with urine abnormalities during the post-vaccination period (Total Vaccinated cohort) Grade 1 Grade 2 Grade 3* Grade 4 Laboratory test** Timing N n % n % n % n % Blood (Erythrocytes or Hemoglobulin) PV1 Day 1 12 1 8.3 0 0.0 0 0.0 0 0.0 Day 7 12 1 8.3 0 0.0 0 0.0 0 0.0 Day 61 10 1 10.0 0 0.0 0 0.0 0 0.0 PV2 Day 7 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 61 21 5 23.8 0 0.0 0 0.0 0 0.0 Day 67 21 4 19.0 0 0.0 0 0.0 0 0.0 PV3 Day 7 23 2 8.7 0 0.0 0 0.0 0 0.0 Day 61 23 9 39.1 0 0.0 0 0.0 0 0.0 Day 67 23 7 30.4 0 0.0 0 0.0 0 0.0 PV4 Day 1 24 6 25.0 0 0.0 0 0.0 0 0.0 Day 7 24 5 20.8 0 0.0 0 0.0 0 0.0 Day 61 24 7 29.2 0 0.0 0 0.0 0 0.0 Day 67 24 7 29.2 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 7 24 3 12.5 0 0.0 0 0.0 0 0.0 Day 61 24 6 25.0 0 0.0 0 0.0 0 0.0 Day 67 24 7 29.2 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 5 20.8 0 0.0 0 0.0 0 0.0 Day 7 24 4 16.7 0 0.0 0 0.0 0 0.0
Day 61 21 7 33.3 0 0.0 0 0.0 0 0.0 Day 67 21 6 28.6 0 0.0 0 0.0 0 0.0 23PPV Day 1 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 23 7 30.4 0 0.0 0 0.0 0 0.0 Day 67 23 4 17.4 0 0.0 0 0.0 0 0.0 Overall parameters PV1 Day 1 12 1 8.3 0 0.0 0 0.0 0 0.0 Day 7 12 1 8.3 0 0.0 0 0.0 0 0.0 Day 61 10 1 10.0 0 0.0 0 0.0 0 0.0 PV2 Day 7 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 61 21 5 23.8 0 0.0 0 0.0 0 0.0 Day 67 21 4 19.0 0 0.0 0 0.0 0 0.0 PV3 Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 23 9 39.1 0 0.0 0 0.0 0 0.0 Day 67 23 7 30.4 0 0.0 0 0.0 0 0.0 PV4 Day 1 24 6 25.0 0 0.0 0 0.0 0 0.0 Day 7 24 5 20.8 0 0.0 0 0.0 0 0.0 Day 61 24 7 29.2 0 0.0 0 0.0 0 0.0 Day 67 24 7 29.2 0 0.0 0 0.0 0 0.0 PV5 Day 1 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 7 24 3 12.5 0 0.0 0 0.0 0 0.0 Day 61 24 6 25.0 0 0.0 0 0.0 0 0.0 Day 67 24 7 29.2 0 0.0 0 0.0 0 0.0 PV6 Day 1 24 5 20.8 0 0.0 0 0.0 0 0.0 Day 7 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 61 21 7 33.3 0 0.0 0 0.0 0 0.0 Day 67 21 6 28.6 0 0.0 0 0.0 0 0.0 23PPV Day 1 24 4 16.7 0 0.0 0 0.0 0 0.0 Day 7 24 2 8.3 0 0.0 0 0.0 0 0.0 Day 61 23 7 30.4 0 0.0 0 0.0 0 0.0 Day 67 23 4 17.4 0 0.0 0 0.0 0 0.0 N= number of subjects with laboratory results at the specified time point n(%)=number(percentage) of subjects with a maximum grade in the given category *Primary outcome variable **Urine parameters were assessed by Reagent-strip testing Primary Efficacy Results: Please refer to the safety section of this CTRS for the results of unsolicited AEs and SAEs Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-PhtD antibodies (ATP cohort for immunogenicity) 391 LU/mL GMC (LU/mL) 95% CI 95% CI Antibody Timing N n % LL UL value LL UL Anti-PhtD PV1 PRE 10 10 100 69.2 100 9996.6 6608.7 15121.2 PI(D30) 10 10 100 69.2 100 11350.7 6928.5 18595.5 PII(D90) 10 10 100 69.2 100 8054.3 5005.4 12960.5 PV2 PRE 24 24 100 85.8 100 17716.4 13160.7 23849.1 PI(D30) 24 24 100 85.8 100 18094.6 13270.3 24672.7 PII(D90) 21 21 100 83.9 100 14378.2 10119.6 20428.9 PV3 PRE 24 24 100 85.8 100 16454.1 11491.1 23560.6 PI(D30) 24 24 100 85.8 100 28636.6 20777.7 39468.1 PII(D90) 23 23 100 85.2 100 37670.6 29311.2 48414.0 PV4 PRE 23 23 100 85.2 100 16800.9 13270.5 21270.5 PI(D30) 24 24 100 85.8 100 37185.5 28847.4 47933.7 PII(D90) 24 24 100 85.8 100 58531.0 49363.7 69400.8 PV5 PRE 24 24 100 85.8 100 13959.0 10649.8 18296.6 PI(D30) 24 24 100 85.8 100 22445.7 17793.5 28314.3 PII(D90) 24 24 100 85.8 100 24312.1 18800.7 31439.3
PV6 PRE 24 24 100 85.8 100 16771.1 11893.3 23649.5 PI(D30) 24 24 100 85.8 100 29021.1 20873.4 40349.0 PII(D90) 21 21 100 83.9 100 40141.6 29095.1 55382.1 23PPV PRE 24 24 100 85.8 100 13119.7 10035.1 17152.5 PI(D30) 24 24 100 85.8 100 12903.5 9567.7 17402.4 PII(D90) 23 23 100 85.2 100 11543.9 8457.8 15756.1 Seropositivity rate = anti-phtd antibody concentration 391 LU/mL GMC = geometric mean antibody concentration N = number of subjects with available results n(%) = number(percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Blood sample before dose 1 PI(D30) = Blood sample 30 days after dose 1 PII(D90) = Blood sample 30 days after dose 2 Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-dPly antibodies (ATP cohort for immunogenicity) 599 LU/mL GMC (LU/mL) 95% CI 95% CI Antibody Timing N n % LL UL value LL UL Anti-dPly PV1 PRE 10 10 100 69.2 100 9197.6 5993.2 14115.4 PI(D30) 10 10 100 69.2 100 22981.9 15630.8 33790.3 PII(D90) 10 10 100 69.2 100 47009.8 30960.2 71379.4 PV2 PRE 24 24 100 85.8 100 15332.5 10750.7 21866.9 PI(D30) 24 24 100 85.8 100 55848.3 37181.4 83886.8 PII(D90) 21 21 100 83.9 100 87300.2 58201.8 130946.6 PV3 PRE 24 24 100 85.8 100 13060.2 9621.1 17728.5 PI(D30) 24 24 100 85.8 100 43980.5 31936.0 60567.7 PII(D90) 23 23 100 85.2 100 63998.6 48405.7 84614.4 PV4 PRE 23 23 100 85.2 100 14904.9 11128.3 19963.0 PI(D30) 24 24 100 85.8 100 90445.0 62893.9 130065.1 PII(D90) 24 24 100 85.8 100 143923.0 106149.6 195138.1 PV5 PRE 24 24 100 85.8 100 12238.7 8648.1 17319.9 PI(D30) 24 24 100 85.8 100 23276.4 16926.3 32008.9 PII(D90) 24 24 100 85.8 100 28560.3 21331.4 38239.1 PV6 PRE 24 24 100 85.8 100 19987.5 15149.1 26371.2 PI(D30) 24 24 100 85.8 100 61346.1 46049.1 81724.5 PII(D90) 21 21 100 83.9 100 73596.9 52250.3 103664.5 23PPV PRE 24 24 100 85.8 100 18661.0 12726.5 27363.0 PI(D30) 24 24 100 85.8 100 18685.4 12612.1 27683.4 PII(D90) 23 23 100 85.2 100 16573.3 11007.1 24954.2 Seropositivity rate = anti-dply antibody concentration 599 LU/mL GMC = geometric mean antibody concentration N = number of subjects with available results n(%) = number (percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Blood sample before dose 1 PI(D30) = Blood sample 30 days after dose 1 PII(D90) = Blood sample 30 days after dose 2 Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-PD antibodies measured by multiplex assay (ATP cohort for immunogenicity) 112 LU/mL GMC (LU/mL) 95% CI 95% CI Antibody Timing N n % LL UL value LL UL Anti-PD PV1 PRE 10 3 30.0 6.7 65.2 88.3 50.5 154.5 PI(D30) 10 3 30.0 6.7 65.2 86.2 50.3 147.7 PII(D90) 10 2 20.0 2.5 55.6 73.7 48.6 111.9
PV2 PRE 24 11 45.8 25.6 67.2 104.7 72.2 151.8 PI(D30) 24 9 37.5 18.8 59.4 93.2 64.5 134.7 PII(D90) 21 5 23.8 8.2 47.2 83.8 55.9 125.7 PV3 PRE 24 8 33.3 15.6 55.3 83.0 64.3 107.3 PI(D30) 24 7 29.2 12.6 51.1 77.7 61.7 98.0 PII(D90) 23 8 34.8 16.4 57.3 78.2 63.2 96.6 PV4 PRE 23 13 56.5 34.5 76.8 108.2 80.6 145.1 PI(D30) 24 9 37.5 18.8 59.4 90.8 68.1 121.1 PII(D90) 24 7 29.2 12.6 51.1 82.1 62.7 107.4 PV5 PRE 24 10 41.7 22.1 63.4 106.8 73.9 154.4 PI(D30) 24 24 100 85.8 100 612.4 409.9 915.1 PII(D90) 24 23 95.8 78.9 99.9 558.3 360.3 865.1 PV6 PRE 24 7 29.2 12.6 51.1 82.3 62.5 108.4 PI(D30) 24 24 100 85.8 100 503.9 366.2 693.3 PII(D90) 21 21 100 83.9 100 628.1 448.7 879.3 23PPV PRE 24 14 58.3 36.6 77.9 131.3 92.2 186.9 PI(D30) 24 14 58.3 36.6 77.9 130.7 91.5 186.9 PII(D90) 23 11 47.8 26.8 69.4 109.9 78.6 153.7 Seropositivity rate = anti-pd antibody concentration 112 LU/mL GMC = geometric mean antibody concentration N = number of subjects with available results n(%) = number (percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Blood sample before dose 1 PI(D30) = Blood sample 30 days after dose 1 PII(D90) = Blood sample 30 days after dose 2 Secondary Outcome Variables: Seropositivity rates and GMCs for Anti-PD antibodies measured by ELISA assay (ATP cohort for immunogenicity) 100 EL.U/mL GMC (EL.U/mL) 95% CI 95% CI Antibody Timing N n % LL UL value LL UL Anti-PD PV1 PRE 10 3 30.0 6.7 65.2 70.9 46.6 107.9 PI(D30) 10 3 30.0 6.7 65.2 72.5 46.7 112.4 PII(D90) 10 3 30.0 6.7 65.2 75.8 46.5 123.5 PV2 PRE 24 7 29.2 12.6 51.1 80.2 54.2 118.7 PI(D30) 24 5 20.8 7.1 42.2 74.9 50.3 111.5 PII(D90) 21 5 23.8 8.2 47.2 83.4 51.0 136.3 PV3 PRE 24 10 41.7 22.1 63.4 82.9 62.3 110.3 PI(D30) 24 10 41.7 22.1 63.4 80.3 61.3 105.1 PII(D90) 23 10 43.5 23.2 65.5 81.8 62.0 107.9 PV4 PRE 23 7 30.4 13.2 52.9 68.4 55.1 85.0 PI(D30) 24 9 37.5 18.8 59.4 73.4 58.7 91.9 PII(D90) 24 7 29.2 12.6 51.1 69.7 54.9 88.6 PV5 PRE 24 8 33.3 15.6 55.3 73.3 57.6 93.2 PI(D30) 24 24 100 85.8 100 406.3 285.0 579.3 PII(D90) 24 23 95.8 78.9 99.9 451.0 314.8 646.2 PV6 PRE 24 6 25.0 9.8 46.7 66.9 53.4 83.8 PI(D30) 24 23 95.8 78.9 99.9 347.6 255.7 472.5 PII(D90) 21 21 100 83.9 100 592.0 433.6 808.4 23PPV PRE 24 13 54.2 32.8 74.4 99.2 73.6 133.8 PI(D30) 24 13 54.2 32.8 74.4 101.0 73.9 137.9 PII(D90) 23 12 52.2 30.6 73.2 96.4 71.2 130.6
Seropositivity rate = anti-pd antibody concentration 100 EL.U/mL GMC = geometric mean antibody concentration N = number of subjects with available results n(%) = number(percentage) of subjects with concentration within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Blood sample before dose 1 PI(D30) = Blood sample 30 days after dose 1 PII(D90) = Blood sample 30 days after dose 2 Secondary Outcome Variables: Seropositivity rates and GMTs for OPSONO-1, OPSONO-4, OPSONO-5, OPSONO- 6B, OPSONO-7F, OPSONO-9V, OPSONO-14, OPSONO-18C, OPSONO-19F and OPSONO-23F antibodies (ATP cohort for immunogenicity) 8 GMT 95% CI 95% CI Antibody Timing N n % LL UL value LL UL OPSONO-1 PV1 PRE 10 3 30.0 6.7 65.2 7.8 3.6 16.8 PI(D30) 10 5 50.0 18.7 81.3 8.9 4.8 16.5 PII(D90) 10 6 60.0 26.2 87.8 16.5 5.8 46.7 PV2 PRE 21 6 28.6 11.3 52.2 9.4 4.8 18.3 PI(D30) 22 13 59.1 36.4 79.3 13.2 7.7 22.7 PII(D90) 21 11 52.4 29.8 74.3 11.8 6.9 20.0 PV3 PRE 23 3 13.0 2.8 33.6 6.5 3.5 12.0 PI(D30) 23 5 21.7 7.5 43.7 7.5 4.0 14.3 PII(D90) 22 6 27.3 10.7 50.2 8.4 4.4 16.4 PV4 PRE 20 8 40.0 19.1 63.9 8.5 5.3 13.4 PI(D30) 24 9 37.5 18.8 59.4 7.8 5.4 11.3 PII(D90) 24 6 25.0 9.8 46.7 6.5 4.5 9.5 PV5 PRE 21 5 23.8 8.2 47.2 7.4 4.2 13.0 PI(D30) 24 23 95.8 78.9 99.9 117.1 67.7 202.5 PII(D90) 24 23 95.8 78.9 99.9 139.4 83.8 231.9 PV6 PRE 22 4 18.2 5.2 40.3 5.7 4.0 8.0 PI(D30) 23 22 95.7 78.1 99.9 91.9 56.0 150.9 PII(D90) 21 21 100 83.9 100 147.3 98.7 219.8 23PPV PRE 21 2 9.5 1.2 30.4 4.6 3.8 5.7 PI(D30) 24 24 100 85.8 100 391.5 193.7 791.4 PII(D90) 23 22 95.7 78.1 99.9 268.6 129.0 559.2 OPSONO-4 PV1 PRE 3 1 33.3 0.8 90.6 14.0 0.1 3085.3 PI(D30) 7 4 57.1 18.4 90.1 47.2 5.2 428.2 PII(D90) 8 3 37.5 8.5 75.5 19.8 3.1 126.1 PV2 PRE 17 3 17.6 3.8 43.4 8.6 3.6 20.5 PI(D30) 18 3 16.7 3.6 41.4 8.2 3.6 19.0 PII(D90) 21 2 9.5 1.2 30.4 6.5 3.2 13.0 PV3 PRE 18 4 22.2 6.4 47.6 10.8 4.1 28.4 PI(D30) 21 5 23.8 8.2 47.2 12.0 4.8 30.3 PII(D90) 22 6 27.3 10.7 50.2 15.2 5.6 41.6 PV4 PRE 15 5 33.3 11.8 61.6 19.0 5.4 67.6 PI(D30) 20 5 25.0 8.7 49.1 14.7 5.0 43.4 PII(D90) 22 5 22.7 7.8 45.4 12.4 4.8 32.2 PV5 PRE 15 6 40.0 16.3 67.7 21.6 6.2 75.5 PI(D30) 24 24 100 85.8 100 3468.8 2091.4 5753.3 PII(D90) 23 23 100 85.2 100 2548.9 1735.9 3742.7 PV6 PRE 17 3 17.6 3.8 43.4 9.3 3.5 24.8 PI(D30) 24 24 100 85.8 100 5327.9 3480.7 8155.3 PII(D90) 21 21 100 83.9 100 3845.0 2573.6 5744.6 23PPV PRE 16 1 6.3 0.2 30.2 5.8 2.6 12.7 PI(D30) 24 24 100 85.8 100 3335.4 1902.8 5846.6 PII(D90) 23 22 95.7 78.1 99.9 1838.2 855.4 3950.4
OPSONO-5 PV1 PRE 7 1 14.3 0.4 57.9 6.1 2.2 17.1 PI(D30) 10 4 40.0 12.2 73.8 9.9 4.0 24.2 PII(D90) 10 4 40.0 12.2 73.8 8.0 3.8 16.9 PV2 PRE 22 2 9.1 1.1 29.2 4.5 3.8 5.4 PI(D30) 21 1 4.8 0.1 23.8 4.4 3.6 5.4 PII(D90) 21 2 9.5 1.2 30.4 4.4 3.8 5.0 PV3 PRE 23 3 13.0 2.8 33.6 5.3 3.7 7.5 PI(D30) 23 2 8.7 1.1 28.0 5.0 3.6 7.1 PII(D90) 23 4 17.4 5.0 38.8 5.7 4.0 8.2 PV4 PRE 23 5 21.7 7.5 43.7 5.3 4.2 6.7 PI(D30) 23 3 13.0 2.8 33.6 4.8 3.9 6.0 PII(D90) 24 5 20.8 7.1 42.2 5.2 4.1 6.5 PV5 PRE 24 4 16.7 4.7 37.4 5.7 4.0 8.1 PI(D30) 23 22 95.7 78.1 99.9 266.9 125.0 569.8 PII(D90) 24 23 95.8 78.9 99.9 212.9 111.2 407.6 PV6 PRE 23 0 0.0 0.0 14.8 4.0 4.0 4.0 PI(D30) 24 23 95.8 78.9 99.9 202.5 116.2 352.8 PII(D90) 21 21 100 83.9 100 225.7 139.7 364.8 23PPV PRE 23 2 8.7 1.1 28.0 5.5 3.5 8.7 PI(D30) 24 24 100 85.8 100 416.9 185.6 936.8 PII(D90) 23 21 91.3 72.0 98.9 180.9 70.3 465.7 OPSONO-6B PV1 PRE 8 7 87.5 47.3 99.7 416.4 75.4 2300.9 PI(D30) 10 7 70.0 34.8 93.3 157.0 23.6 1043.7 PII(D90) 10 7 70.0 34.8 93.3 160.6 24.7 1043.0 PV2 PRE 14 10 71.4 41.9 91.6 161.3 37.7 689.9 PI(D30) 22 16 72.7 49.8 89.3 145.3 50.0 422.3 PII(D90) 21 15 71.4 47.8 88.7 172.6 52.4 568.6 PV3 PRE 11 7 63.6 30.8 89.1 101.5 16.9 608.0 PI(D30) 21 16 76.2 52.8 91.8 207.8 69.8 618.9 PII(D90) 23 16 69.6 47.1 86.8 151.9 50.1 460.8 PV4 PRE 10 5 50.0 18.7 81.3 52.2 7.3 375.0 PI(D30) 22 12 54.5 32.2 75.6 70.5 21.0 236.1 PII(D90) 23 11 47.8 26.8 69.4 55.3 16.1 190.3 PV5 PRE 13 10 76.9 46.2 95.0 144.9 37.6 558.8 PI(D30) 24 24 100 85.8 100 991.5 583.3 1685.2 PII(D90) 24 24 100 85.8 100 1202.7 792.4 1825.3 PV6 PRE 12 8 66.7 34.9 90.1 122.9 23.3 648.5 PI(D30) 24 24 100 85.8 100 1775.1 961.8 3276.3 PII(D90) 21 21 100 83.9 100 1935.8 1193.7 3139.2 23PPV PRE 10 7 70.0 34.8 93.3 141.7 22.4 897.5 PI(D30) 23 22 95.7 78.1 99.9 1724.5 837.6 3550.7 PII(D90) 23 21 91.3 72.0 98.9 940.3 399.2 2214.7 OPSONO-7F PV1 PRE 8 8 100 63.1 100 892.7 407.2 1957.3 PI(D30) 9 9 100 66.4 100 958.0 453.6 2023.3 PII(D90) 10 10 100 69.2 100 892.6 443.1 1798.0 PV2 PRE 17 15 88.2 63.6 98.5 722.7 229.1 2279.9 PI(D30) 24 22 91.7 73.0 99.0 837.0 380.0 1843.6 PII(D90) 20 19 95.0 75.1 99.9 1277.2 567.4 2875.2 PV3 PRE 14 12 85.7 57.2 98.2 717.7 179.5 2869.1 PI(D30) 24 23 95.8 78.9 99.9 916.1 465.2 1804.2 PII(D90) 23 21 91.3 72.0 98.9 886.8 376.7 2087.3 PV4 PRE 17 16 94.1 71.3 99.9 1081.2 468.0 2497.9 PI(D30) 24 24 100 85.8 100 1264.9 895.7 1786.3 PII(D90) 24 24 100 85.8 100 1820.0 1218.9 2717.5 PV5 PRE 11 11 100 71.5 100 2107.1 964.6 4602.7 PI(D30) 24 24 100 85.8 100 3239.0 2209.1 4749.1
PII(D90) 24 24 100 85.8 100 4547.2 3105.4 6658.4 PV6 PRE 12 11 91.7 61.5 99.8 764.2 193.3 3022.0 PI(D30) 24 24 100 85.8 100 4668.3 2811.9 7750.4 PII(D90) 21 21 100 83.9 100 6056.7 4211.8 8709.6 23PPV PRE 14 12 85.7 57.2 98.2 586.5 156.8 2194.4 PI(D30) 22 22 100 84.6 100 6960.6 4531.6 10691.5 PII(D90) 23 23 100 85.2 100 4886.4 2956.8 8075.1 OPSONO-9V PV1 PRE 9 9 100 66.4 100 237.7 128.4 439.9 PI(D30) 10 10 100 69.2 100 276.1 149.9 508.5 PII(D90) 10 10 100 69.2 100 263.2 157.7 439.4 PV2 PRE 19 17 89.5 66.9 98.7 204.3 87.4 477.8 PI(D30) 22 18 81.8 59.7 94.8 152.2 61.8 375.2 PII(D90) 21 17 81.0 58.1 94.6 189.8 70.7 510.0 PV3 PRE 22 21 95.5 77.2 99.9 313.3 163.8 599.3 PI(D30) 24 23 95.8 78.9 99.9 288.1 156.1 531.5 PII(D90) 22 21 95.5 77.2 99.9 322.7 168.8 616.8 PV4 PRE 21 21 100 83.9 100 255.0 161.0 403.9 PI(D30) 22 21 95.5 77.2 99.9 313.9 164.5 598.8 PII(D90) 23 22 95.7 78.1 99.9 330.8 173.8 629.6 PV5 PRE 24 22 91.7 73.0 99.0 216.7 103.5 453.8 PI(D30) 24 24 100 85.8 100 2037.4 1208.5 3434.7 PII(D90) 24 24 100 85.8 100 3915.8 2467.4 6214.3 PV6 PRE 22 22 100 84.6 100 271.2 177.8 413.6 PI(D30) 24 24 100 85.8 100 2666.3 1586.8 4480.2 PII(D90) 21 21 100 83.9 100 5498.0 3334.3 9065.8 23PPV PRE 20 19 95.0 75.1 99.9 304.4 148.5 624.0 PI(D30) 24 24 100 85.8 100 3945.9 2390.3 6514.1 PII(D90) 23 23 100 85.2 100 2659.0 1463.6 4830.9 OPSONO-14 PV1 PRE 9 8 88.9 51.8 99.7 259.2 67.5 994.5 PI(D30) 9 8 88.9 51.8 99.7 397.6 97.5 1621.7 PII(D90) 10 9 90.0 55.5 99.7 372.6 110.6 1255.5 PV2 PRE 18 16 88.9 65.3 98.6 174.0 76.4 396.3 PI(D30) 22 20 90.9 70.8 98.9 248.7 122.3 505.7 PII(D90) 21 19 90.5 69.6 98.8 290.6 134.4 628.3 PV3 PRE 20 17 85.0 62.1 96.8 218.2 85.7 555.5 PI(D30) 21 19 90.5 69.6 98.8 307.4 134.8 701.0 PII(D90) 21 19 90.5 69.6 98.8 373.3 167.3 832.9 PV4 PRE 14 13 92.9 66.1 99.8 314.5 126.7 780.2 PI(D30) 20 18 90.0 68.3 98.8 225.2 98.1 517.2 PII(D90) 21 20 95.2 76.2 99.9 411.5 215.1 787.5 PV5 PRE 17 17 100 80.5 100 618.2 364.9 1047.4 PI(D30) 24 24 100 85.8 100 2968.1 1713.8 5140.3 PII(D90) 24 24 100 85.8 100 3045.5 2007.2 4620.9 PV6 PRE 16 15 93.8 69.8 99.8 245.2 116.4 516.5 PI(D30) 24 24 100 85.8 100 2559.1 1651.0 3966.7 PII(D90) 21 21 100 83.9 100 2944.8 1854.0 4677.5 23PPV PRE 20 19 95.0 75.1 99.9 308.4 164.8 576.8 PI(D30) 24 24 100 85.8 100 3058.8 1829.4 5114.2 PII(D90) 22 22 100 84.6 100 2551.9 1518.7 4287.9 OPSONO-18C PV1 PRE 10 4 40.0 12.2 73.8 22.3 4.5 111.2 PI(D30) 9 3 33.3 7.5 70.1 20.1 3.1 130.7 PII(D90) 10 3 30.0 6.7 65.2 13.1 3.2 53.8 PV2 PRE 18 4 22.2 6.4 47.6 10.0 3.9 25.7 PI(D30) 21 7 33.3 14.6 57.0 11.9 5.2 27.2 PII(D90) 17 6 35.3 14.2 61.7 11.9 4.8 29.6 PV3 PRE 15 3 20.0 4.3 48.1 6.4 3.3 12.7
PI(D30) 20 9 45.0 23.1 68.5 23.4 8.6 64.0 PII(D90) 22 8 36.4 17.2 59.3 15.8 6.3 39.9 PV4 PRE 15 7 46.7 21.3 73.4 14.2 5.9 34.2 PI(D30) 24 14 58.3 36.6 77.9 32.7 14.2 75.4 PII(D90) 20 9 45.0 23.1 68.5 20.4 7.9 52.7 PV5 PRE 18 6 33.3 13.3 59.0 11.0 5.2 23.3 PI(D30) 24 23 95.8 78.9 99.9 562.2 286.0 1105.0 PII(D90) 24 24 100 85.8 100 928.5 613.2 1405.8 PV6 PRE 20 4 20.0 5.7 43.7 9.0 4.1 19.6 PI(D30) 24 24 100 85.8 100 1132.3 750.8 1707.6 PII(D90) 21 21 100 83.9 100 1830.0 1220.6 2743.7 23PPV PRE 18 4 22.2 6.4 47.6 9.3 4.1 20.8 PI(D30) 24 23 95.8 78.9 99.9 454.3 217.1 950.7 PII(D90) 22 20 90.9 70.8 98.9 311.6 134.9 719.5 OPSONO-19F PV1 PRE 10 4 40.0 12.2 73.8 9.2 4.0 21.4 PI(D30) 8 1 12.5 0.3 52.7 5.2 2.8 9.8 PII(D90) 10 5 50.0 18.7 81.3 8.0 4.7 13.7 PV2 PRE 20 10 50.0 27.2 72.8 15.0 7.2 31.4 PI(D30) 23 10 43.5 23.2 65.5 11.6 6.1 21.9 PII(D90) 21 11 52.4 29.8 74.3 16.7 7.9 35.5 PV3 PRE 19 13 68.4 43.4 87.4 17.8 9.8 32.3 PI(D30) 23 12 52.2 30.6 73.2 13.5 7.0 25.7 PII(D90) 23 14 60.9 38.5 80.3 16.6 8.4 32.8 PV4 PRE 21 8 38.1 18.1 61.6 10.4 5.7 19.2 PI(D30) 23 8 34.8 16.4 57.3 7.9 4.9 12.6 PII(D90) 24 10 41.7 22.1 63.4 11.3 5.9 21.7 PV5 PRE 21 10 47.6 25.7 70.2 19.7 7.8 49.8 PI(D30) 21 21 100 83.9 100 690.6 374.4 1273.7 PII(D90) 24 24 100 85.8 100 992.1 532.9 1847.2 PV6 PRE 20 11 55.0 31.5 76.9 15.2 7.7 30.1 PI(D30) 23 23 100 85.2 100 2218.9 1351.2 3643.6 PII(D90) 21 21 100 83.9 100 2179.0 1404.4 3380.9 23PPV PRE 20 7 35.0 15.4 59.2 7.6 4.9 11.7 PI(D30) 20 20 100 83.2 100 412.5 189.4 898.4 PII(D90) 23 22 95.7 78.1 99.9 311.7 141.7 685.6 OPSONO-23F PV1 PRE 6 6 100 54.1 100 1712.3 705.1 4158.6 PI(D30) 9 9 100 66.4 100 1109.5 425.5 2893.0 PII(D90) 10 9 90.0 55.5 99.7 581.3 126.3 2674.8 PV2 PRE 16 11 68.8 41.3 89.0 160.5 40.0 644.8 PI(D30) 19 14 73.7 48.8 90.9 220.0 66.0 733.8 PII(D90) 18 14 77.8 52.4 93.6 217.7 70.9 668.3 PV3 PRE 12 8 66.7 34.9 90.1 188.0 29.2 1211.0 PI(D30) 21 16 76.2 52.8 91.8 295.1 92.9 937.5 PII(D90) 19 16 84.2 60.4 96.6 507.4 170.4 1510.5 PV4 PRE 9 6 66.7 29.9 92.5 215.5 17.6 2635.2 PI(D30) 21 19 90.5 69.6 98.8 555.9 230.5 1340.8 PII(D90) 22 18 81.8 59.7 94.8 421.5 140.9 1261.0 PV5 PRE 19 13 68.4 43.4 87.4 240.5 58.6 987.6 PI(D30) 24 24 100 85.8 100 1968.9 1256.5 3085.1 PII(D90) 24 24 100 85.8 100 1882.9 1176.2 3014.3 PV6 PRE 17 12 70.6 44.0 89.7 235.4 55.6 996.7 PI(D30) 24 24 100 85.8 100 3306.3 2280.7 4793.1 PII(D90) 21 21 100 83.9 100 2987.4 1977.1 4513.9 23PPV PRE 15 11 73.3 44.9 92.2 236.9 56.8 988.4 PI(D30) 24 24 100 85.8 100 2024.2 1237.8 3310.1 PII(D90) 23 22 95.7 78.1 99.9 1559.7 778.7 3123.8