Phase 3 Randomized, Multicenter, Placebo-Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Randomization
2.2. Study Vaccine Administration
2.3. Study Participants
2.4. Study Objectives and Endpoints
2.5. Statistical Methods
3. Results
3.1. Study Population
3.2. Coprimary Objectives: Lot-to-Lot Consistency and CBER Criteria
3.3. Immunogenicity
3.4. Safety
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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aH5N1c a | ||||||
---|---|---|---|---|---|---|
Group A (n = 804) | Group B (n = 799) | Group C (n = 795) | All aH5N1c (n = 2398) | Placebo (n = 798) | Total (N = 3196) | |
Mean age ± SD, years | 58.1 ± 17.67 | 57.5 ± 17.83 | 57.5 ± 18.24 | 57.7 ± 17.91 | 57.7 ± 18.29 | 57.7 ± 18.00 |
Age group, n (%) | ||||||
18 to <65 years | 403 (50.1) | 399 (49.9) | 397 (49.9) | 1199 (50.0) | 398 (49.9) | 1597 (50.0) |
≥65 years | 401 (49.9) | 400 (50.1) | 398 (50.1) | 1199 (50.0) | 400 (50.1) | 1599 (50.0) |
Female, n (%) | 444 (55.2) | 434 (54.3) | 447 (56.2) | 1325 (55.3) | 438 (54.9) | 1763 (55.2) |
Race, n (%) | ||||||
White | 668 (83.1) | 679 (85.0) | 674 (84.8) | 2021 (84.3) | 665 (83.3) | 2686 (84.0) |
Black | 110 (13.7) | 102 (12.8) | 104 (13.1) | 316 (13.2) | 112 (14.0) | 428 (13.4) |
Asian | 12 (1.5) | 7 (0.9) | 9 (1.1) | 28 (1.2) | 7 (0.9) | 35 (1.1) |
Native American or Alaskan Native | 6 (0.7) | 4 (0.5) | 5 (0.6) | 15 (0.6) | 3 (0.4) | 18 (0.6) |
Native Hawaiian or other Pacific Islander | 3 (0.4) | 2 (0.3) | 1 (0.1) | 6 (0.3) | 4 (0.5) | 10 (0.3) |
Other | 5 (0.6) | 5 (0.6) | 2 (0.3) | 12 (0.5) | 7 (0.9) | 19 (0.6) |
Hispanic ethnicity, n (%) | 53 (6.6) | 61 (7.6) | 64 (8.1) | 178 (7.4) | 55 (6.9) | 233 (7.3) |
Mean weight ± SD, kg | 78.86 ± 15.0 | 80.22 ± 15.2 | 78.86 ± 15.3 | 79.31 ± 15.2 | 79.84 ± 15.3 | 79.44 ± 15.2 |
Mean BMI ± SD, kg/m2 | 27.40 ± 4.2 | 27.86 ± 4.1 | 27.41± 4.2 | 27.56 ± 4.2 | 27.60 ± 4.2 | 27.57 ± 4.2 |
Previous influenza vaccine in past 12 months, n (%) | ||||||
All subjects | 430 (53.5) | 416 (52.1) | 426 (53.6) | 1272 (53.0) | 422 (52.9) | 1694 (53.0) |
Age 18 to <65 years | 145 (36.0) | 137 (34.3) | 139 (35.0) | 421 (35.1) | 123 (30.9) | 544 (34.1) |
Age ≥65 years | 285 (71.1) | 279 (69.8) | 287 (72.1) | 851 (71.0) | 299 (74.8) | 1150 (71.9) |
18 to <65 Years | ≥65 Years | Total Population | ||||
---|---|---|---|---|---|---|
aH5N1c | Placebo | aH5N1c | Placebo | aH5N1c | Placebo | |
Day 1, n | 1116 | 372 | 1133 | 367 | 2249 | 739 |
GMT (95% Cl) | 13.5 (12.8–14.2) | 13.7 (12.5- 15.0) | 20.5 (19.4–21.8) | 20.6 (18.6–22.7) | 16.6 (16.0–17.3) | 16.7 (15.6–17.9) |
Day 22, n | 1115 | 370 | 1130 | 366 | 2245 | 736 |
GMT (95% Cl) | 50.6 (47.6–53.8) | 11.6 (10.4–12.9) | 42.4 (40.0–45.0) | 14.5 (13.1–16.0) | 46.4 (44.5–48.4) | 13.0 (12.1–14.0) |
GMR Day 22/Day 1 (95% Cl) | 3.81 (3.58–4.05) | 0.87 (0.79–0.97) | 2.14 (2.02–2.27) | 0.73 (0.66–0.81) | 2.86 (2.74–2.98) | 0.80 (0.74–0.86) |
Day 43, n | 1076 | 349 | 1080 | 351 | 2156 | 700 |
GMT (95% Cl) | 170.7 (160.5–181.6) | 11.0 (9.9–12.2) | 97.9 (92.1–104.1) | 16.7 (15.0–18.5) | 130.6 (124.8–136.6) | 13.7 (12.6–14.8) |
GMR Day 43/Day 1 (95% Cl) | 12.70 (11.94–13.51) | 0.82 (0.73–0.91) | 4.90 (4.61–5.20) | 0.83 (0.75–0.92) | 7.96 (7.61–8.33) | 0.83 (0.77–0.90) |
Day 183, n | 1025 | 341 | 1054 | 346 | 2079 | 687 |
GMT (95% Cl) | 20.4 (19.3–21.6) | 6.8 (6.1–7.4) | 19.3 (18.2–20.4) | 8.6 (7.8–9.5) | 20.0 (19.2–20.8) | 7.7 (7.2–8.2) |
GMR Day 183/Day 1 (95% Cl) | 1.53 (1.44–1.61) | 0.51 (0.46–0.56) | 0.97 (0.91–1.02) | 0.43 (0.39–0.47) | 1.22 (1.17–1.27) | 0.47 (0.44–0.50) |
Age 18 to <65 Years | Age ≥65 Years | Total Population | ||||
---|---|---|---|---|---|---|
aH5N1c | Placebo | aH5N1c | Placebo | aH5N1c | Placebo | |
Day 22, n | 1115 | 370 | 1130 | 366 | 2245 | 736 |
Seroconversion, % (95% CI) | 40.4 (37.6–43.4) | 1.9 (0.8–3.9) | 24.2 (21.7–26.8) | 0.3 (0.0–1.5) | 32.2 (30.3–34.2) | 1.1 (0.5–2.1) |
Day 43, n | 1076 | 349 | 1080 | 351 | 2156 | 700 |
Seroconversion, % (95% CI) | 79.9 (77.4–82.3) | 0.3 (0.0–1.6) | 54.0 (51.0–57.0) | 1.7 (0.6–3.7) | 66.9 (64.9–68.9) | 1.0 (0.4–2.0) |
Day 183, n | 1025 | 341 | 1054 | 346 | 2079 | 687 |
Seroconversion, % (95% CI) | 16.2 (14.0–18.6) | 0.3 (0.0–1.6) | 8.0 (6.4–9.8) | 1.2 (0.3–2.9) | 12.0 (10.7–13.5) | 0.7 (0.2–1.7) |
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Peterson, J.; Van Twuijver, E.; Versage, E.; Hohenboken, M. Phase 3 Randomized, Multicenter, Placebo-Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects. Vaccines 2022, 10, 497. https://doi.org/10.3390/vaccines10040497
Peterson J, Van Twuijver E, Versage E, Hohenboken M. Phase 3 Randomized, Multicenter, Placebo-Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects. Vaccines. 2022; 10(4):497. https://doi.org/10.3390/vaccines10040497
Chicago/Turabian StylePeterson, James, Esther Van Twuijver, Eve Versage, and Matthew Hohenboken. 2022. "Phase 3 Randomized, Multicenter, Placebo-Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects" Vaccines 10, no. 4: 497. https://doi.org/10.3390/vaccines10040497