Assessment of immunogenicity and safety across two manufacturing lots of a 3-antigen hepatitis B vaccine, Sci-B-Vac®, compared with Engerix-B® in healthy Asian adults: A phase 3 randomized clinical trial

3区 · 医学

Article

作者: Diaz-Mitoma, Francisco ; Popovic, Vlad ; Spaans, Johanna N

BACKGROUNDSci-B-Vac®, a 3-antigen hepatitis B vaccine (3A-HBV), contains all three recombinant hepatitis B virus (HBV) envelope proteins (S, pre-S1, and pre-S2). In 2005, 3A-HBV manufacturing transferred facilities (A to B), where it continues to be manufactured.METHODSThis phase 3, single-blind, randomized study, conducted at one site in Vietnam, compared efficacy and safety among two 3A-HBV lots, lot A and lot B, and a single-antigen hepatitis B vaccine (1A-HBV), Engerix-B®. Primary objective was to demonstrate equivalence at day 210 of two 3A-HBV lots in seroprotection rate (SPR; defined as percentage of participants achieving hepatitis B surface antigen antibody [anti-HBs] titers ≥ 10 mIU/mL). Secondary objectives were assessing immunogenicity at days 180, 210, and 360, and safety of 3A-HBV.RESULTS3A-HBV SPR equivalence was demonstrated at day 210 (lot A: 97.3% [95% CI: 92.4%, 99.4%] vs. lot B: 100.0% [97.0%, 100.0%]). Compared to 1A-HBV, lot B SPR was higher at day 180 (98.3% vs. 81.2%; difference: 17.1% [9.7%, 24.6%]) and non-inferior at day 210 (100% vs. 98.3%; difference: 1.7% [-0.6%, 4.1%]). 3A-HBV lot B showed the same SPR after 2 doses (98.3%) as 1A-HBV after 3 doses (98.3%). Adverse events (AEs) were comparable with both 3A-HBV lots (lot A: 68.7% vs. lot B: 54.2%), but higher than 1A-HBV (35.3%). Vaccination-related AEs included transient injection site pain (38.9%), myalgia (9.3%), and fatigue (7.5%). Eight serious AEs were reported (lot A: 3/134 [2.2%]; lot B: 1/134 [0.8%]; 1A-HBV: 4/133 [2.3%]). One serious AE, syncope, was noted as probably related to study vaccine, lot B.CONCLUSIONSThe two 3A-HBV lots had equivalent immunogenicity, but lot B elicited faster onset of seroprotection and higher anti-HBs titers than both lot A and 1A-HBV in an Asian population. This supports 3A-HBV lot B as an effective choice for HBV vaccination, with a favorable safety profile. ClinicalTrials.gov: NCT04531098.

项与 Single-shot hepatitis B virus vaccine(OctoPlus/SciGen) 相关的新闻（医药）

2022-06-14

·PRNewswire

Zhimeng Biopharma will report positive phase 1b trial results on its HBV capsid inhibitor ZM-H1505R in the upcoming International Liver Congress

SHANGHAI, June 14, 2022 /PRNewswire/ -- Shanghai Zhimeng Biopharma announces that it will report the positive results obtained from a phase 1b study on its HBV capsid inhibitor ZM-H1505R in the International Liver Congress in June 22-26, 2022 (the EASL meeting). The recently completed phase 1b study was to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antiviral activity of ZM-H1505R in a double-blind, randomized, placebo-controlled, dose escalating study in treatment-naïve chronic hepatitis B (CHB) patients. Patients were divided into three cohorts (10 patients each) and randomized within each cohort in a ratio of 4:1 to receive an ascending dose of 50, 100, or 200 mg of ZM-H1505R, or placebo once a day for 28 consecutive days. ZM-H1505R was safe and well tolerated within this dose range, with most AEs being mild to moderate in severity. No SAE was observed and there was no withdrawal due to AE. A proportional relationship was observed between dose and plasma exposure of ZM-H1505R. At day 28, the mean plasma Cmin were 2.73, 7.05, and 14.56 folds of its protein-binding adjusted HBV DNA EC50 for 50, 100, and 200 mg doses, respectively. Serum levels of HBV DNA and HBV pgRNA were significantly reduced from baselines after 28 days of treatment with ZM-H1505R. The mean maximal reductions from baselines in HBV DNA were -1.54, -2.50 and -2.75 log10 IU/mL, and in HBV pgRNA were -1.53, -2.35 and -2.34 log10 IU/mL in the 50, 100 and 200 mg cohorts, respectively. The mean maximal declines from baseline in HBcrAg were -0.61 and -0.51 log10 IU/mL in the 100 and 200 mg cohorts, respectively. "We are pleased to see the positive safety and preliminary efficacy results of ZM-H1505R from this phase 1b study." Commented Dr. Huanming Chen, CEO of Zhimeng Biopharma. "We believe that HBV capsid inhibitors such as ZM-H1505R will play an important role in further reducing the viruses in patients who have been treated with a NA for a long time but still have low levels of viremia. We are also confident that ZM-H1505R may become a component of a combination therapy for functional cure of CHB. With such promising results of ZM-H1505R, we will initiate a phase 2 trial in Q3 of 2022 to further evaluate its safety and efficacy". About ZM-H1505R ZM-H1505R is a small-molecule HBV capsid assembly modulator with a novel pyrazole structure currently being evaluated for the treatment of chronic hepatitis B (CHB). It is active against most HBV variants that show resistance to other HBV capsid modulators. About Zhimeng Biopharma Zhimeng Biopharma is a clinical-stage biopharmaceutical company committed to developing innovative drugs for the treatment of chronic hepatitis B (CHB) and severe neurological diseases with significant unmet medical needs. The company has recently announced the launch of the first-in-human phase I study of its novel TLR8 agonist, developed for CHB, in the US in March 2022; and the first-in-human phase I study of its novel small molecule, KCNQ2/3 selective opener, developed for the treatment of refractory epilepsy, in the US in May 2022. For more information, please visit: SOURCE Shanghai Zhimeng Biopharma, Inc.

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100 项与 Single-shot hepatitis B virus vaccine(OctoPlus/SciGen) 相关的药物交易

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