A phase 3 study of a short, two dose regimen of an investigational Hepatitis B vaccine
Bibliographic record
Abstract
Background: Achieving rapid protection against hepatitis B can be critical for travellers. HBsAg-ISS (HEPLISAV™) is an investigational vaccine containing Hepatitis B surface antigen (HBsAg) and 1018 Immunostimulatory Sequence (ISS), a Toll-like Receptor 9 (TLR9) agonist adjuvant. A Phase 3 study of subjects 18-55 years of age demonstrated non-inferiority of a short, 2 dose regimen of HBsAg-ISS to a 3 dose regimen of a licensed vaccine. This analysis in subjects >40 years of age compares the seroprotection rate (SPR), measured by antibody to HBsAg [anti-HBsAg] ≥10 mIU/mL, and anti-HBsAg geometric mean concentration (GMC) of HBsAg-ISS with licensed vaccine (Engerix-B, 20 mcg). This study demonstrated that the SPR of a short, 2 dose regimen of HBsAg-ISS in subjects 18-55 and in subjects over 40 is superior to the standard regimen of Engerix-B. This vaccine could provide a better solution for clinicians needing rapid, safe and effective protection against hepatitis B disease for travelers. Methods: A randomized observer-blind study comparing 2 doses of HBsAg-ISS at months 0 and 1 with saline placebo at month 6 to 3 doses of licensed vaccine at months 0, 1, and 6. Anti-HBsAg were measured at months 0, 1, 2, 3, 6, and 7. Safety, including local and systemic reactogenicity and adverse events was assessed. Results: 2101 subjects, including 1188 subjects over age 40, were included in the per-protocol analysis in a 3:1 randomization of HBsAg-ISS to Engerix-B. The primary endpoint SPR for all subjects was statistically significantly higher for HBsAg-ISS (95% at month 3) vs. Engerix-B (81% at month 7) [p < 0.0001]. For subjects over age 40 the primary endpoint SPR was 92% for HBsAg-ISS and 75% for Engerix-B) [p < 0.0001]; the GMC (mIU/mL) at month 7 was 236 for HBsAg-ISS and 218 for Engerix-B. HBsAg-ISS was safe, well-tolerated and comparable to Engerix-B with regard to local and systemic adverse events and serious adverse events. Two cases of ANCA-associated vasculitis were observed; one in an HBsAg-ISS subject and one in an Engerix-B subject. A review of AEs potentially associated with autoimmune conditions revealed no difference between groups. Conclusion: This study demonstrated that the SPR of a short, 2 dose regimen of HBsAg-ISS in subjects 18-55 and in subjects over 40 is superior to the standard regimen of Engerix-B. This vaccine could provide a better solution for clinicians needing rapid and safe protection against hepatitis B disease for travelers. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".