E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute hepatitis B without delta-agent and without hepatic coma
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019731 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objectives: Among healthy adults who receive the vaccine at 0, 1, and 6 months, to demonstrate that: (1) three lots of process upgrade hepatitis B vaccine (process upgrade vaccine) induce similar responses in antibody to hepatitis B surface antigen (anti-HBs), as measured by seroprotection rate (SPR) one month after the third dose, (2) one month after the third dose, the combined process upgrade lots will exhibit an adequate seroprotection rate, and (3) one month after the third dose, the anti-HBs geometric mean titer (GMT) for the process upgrade vaccine is improved, or at least non-inferior, when compared to the current process hepatitis B vaccine (current process vaccine).
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E.2.2 | Secondary objectives of the trial |
Secondary objective: To assess the safety and tolerability of the process upgrade vaccine in healthy adults.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Twenty to 35 years of age. 2. In general good health based on a medical history taken on Day 1 prior to receiving the first injection of vaccine. Any underlying chronic illness must be documented to be in stable condition. 3. For women, a negative urine pregnancy test just prior to vaccination on Day 1.
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E.4 | Principal exclusion criteria |
1. History of previous hepatitis B infection. 2. History of vaccination with any hepatitis B vaccine. 3. Recent (less than 72 hours) history of febrile illness (oral temperature ≥37.7ºC/100.0ºF). 4. Known or suspected hypersensitivity to any component of RECOMBIVAX HB vaccine (e.g., aluminum, yeast). 5. Recent administration (within 3 months prior to first injection with the study vaccine) of hepatitis B immune globulin (HBIG), serum immune globulin, or any other blood-derived product. 6. Receipt of licensed inactivated vaccines within 14 days prior to first injection with the study vaccine. Receipt of licensed live virus vaccines within the 30 days prior to injection with the study vaccine. 7. Receipt of investigational drugs or other investigational vaccines within 3 months prior to first injection with the study vaccine. 8. Known or suspected impairment of immunologic function or recent use of immunomodulatory medications (e.g., systemic corticosteroids). Does not include topical and inhaled steroids. 9. Pregnant women, nursing mothers, and women planning to become pregnant within the study period. 10. Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Hypotheses: 1) The three lots of process upgrade vaccine will, when administered to healthy young adults on a 0, 1, and 6 month schedule, induce similar seroprotection rates to hepatitis B one month post-vaccination. (The primary endpoint for the demonstration of consistency will be the seroprotection rate (an anti-HBs titer ≥ 10 mIU/mL) at 7 months, one month after the third dose of vaccine. The criterion for consistency of the three lots of process upgrade vaccine is that the anti-HBs seroprotection rate will not differ statistically by more than 10 percentage points between any pair of lots.) 2) The three pooled process upgrade vaccine lots will, when administered to healthy young adults on a 0, 1, and 6 month schedule, induce an adequate immune response to hepatitis B one month post vaccination. (The criterion for an adequate response requires ruling out 90.0% by the lower bound of a one-sided 97.5% confidence interval for the anti-HBs seroprotection rate one month after the third dose for the pooled process upgrade lots.) 3A) The process upgrade vaccine, when administered to healthy young adults on a 0, 1, and 6 month schedule, will be non-inferior to the current process vaccine with respect to the anti-HBs GMT at 7 months, one month after the third dose. (The non-inferiority criterion requires ruling out a 1.5-fold decrease in the ratio of GMTs (GMTupgrade/GMTcurrent) at 7 months.) 3B) Conditional upon acceptance of 3A, the process upgrade vaccine will be superior to the current process vaccine with respect to the anti-HBs GMT one month after the third dose. (The superiority criterion requires ruling out a GMT ratio (GMTupgrade/GMTcurrent) of 1.0 at 7 months.)
Secondary Hypothesis: 1) The process upgrade vaccine will be generally well tolerated when compared with the current process vaccine.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Immunogenicity and Lot Consistency |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A subject is defined as having completed the study when all scheduled vaccinations have been received, the safety follow-up completed, and the post-Dose 3 blood sample obtained. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |