Clinical Trial Results:
A Study in Healthy Neonates of Safety, Tolerability, and Immunogenicity of Recombinant Hepatitis B Vaccine Manufactured Using a Modified Process
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Summary
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EudraCT number |
2016-003981-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
20 Jul 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Feb 2017
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First version publication date |
03 Feb 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
V232-056
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00322361 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Merck Registration Number: 2006_007 | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Jul 2007
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Jul 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Jul 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Hepatitis B Vaccine [Recombinant] is a well established vaccine which has been used extensively, worldwide since its initial licensure in 1986. Hepatitis B vaccines: [1] induce protection against the morbidity and mortality of acute hepatitis B virus infection, [2] reduce the incidence of chronic infection in vaccinated populations, and [3] thereby, reduce the incidence of hepatocellular carcinoma. The purpose of the trial was to assess if the new manufacturing process of the Hepatitis B Vaccine [Recombinant] vaccine showed the same or better level of hepatitis B antibody response than does the currently licensed Hepatitis B Vaccine [Recombinant] vaccine. This study was also to confirm that the new process vaccine is as well tolerated as the current vaccine in neonates.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
The following additional measure defined for this individual study was in place for the protection of trial participants: participants who did not develop seroprotective levels of anti-HBs, 1 month after the third dose, may have been offered additional vaccination, outside of the protocol, at the discretion of the investigator.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 May 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 35
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Country: Number of subjects enrolled |
United States: 531
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Worldwide total number of subjects |
566
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
566
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Healthy male and female full-term (37-42 weeks gestation) neonates (birth to 10 days of age) born to mothers with documented negative test for hepatitis B surface antigen (HBsAg) within 9 months prior to delivery. | |||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
No pre-screening for antibody to hepatitis B surface antigen (anti-HBs) or hepatitis B core antigen (anti-HBc) was conducted. | |||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Modified Process Hepatitis B Vaccine | |||||||||||||||||||||||||||||||||||||||
Arm description |
Modified Process Hepatitis B three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Modified Process Hepatitis B Vaccine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
5 mcg (0.5 mL) per dose
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Arm title
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RECOMBIVAX HB™ Vaccine | |||||||||||||||||||||||||||||||||||||||
Arm description |
RECOMBIVAX HB™ three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1. | |||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
RECOMBIVAX HB™ Vaccine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
5 mcg (0.5 mL) per dose
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Baseline characteristics reporting groups
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Reporting group title |
Modified Process Hepatitis B Vaccine
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Reporting group description |
Modified Process Hepatitis B three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
RECOMBIVAX HB™ Vaccine
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Reporting group description |
RECOMBIVAX HB™ three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Modified Process Hepatitis B Vaccine
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Reporting group description |
Modified Process Hepatitis B three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1. | ||
Reporting group title |
RECOMBIVAX HB™ Vaccine
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Reporting group description |
RECOMBIVAX HB™ three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1. | ||
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End point title |
Geometric mean titer (GMT) to anti-HBs at Month 7 | ||||||||||||
End point description |
Geometric mean antibody titers to hepatitis B surface antigen (milli international units/milliliter [mIU/mL]) were measured 4 weeks after the third vaccination. Analysis population: per-protocol population included all participants who met the inclusion criteria, were not protocol violators and had serology and vaccinations within the specified day ranges.
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End point type |
Primary
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End point timeframe |
Month 7 (1 month post vaccination 3)
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Statistical analysis title |
GMT ratio | ||||||||||||
Statistical analysis description |
The lower bound of the 95% confidence interval (CI) on the GMT ratio greater than the pre-specified clinically relevant values of 0.67 (i.e., a 1.5-fold decrease) and 1.00 (identity) allows for a conclusion of non-inferiority or superiority, respectively.
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Comparison groups |
Modified Process Hepatitis B Vaccine v RECOMBIVAX HB™ Vaccine
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Number of subjects included in analysis |
378
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
Method |
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Parameter type |
GMT ratio | ||||||||||||
Point estimate |
1.26
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.94 | ||||||||||||
upper limit |
1.69 | ||||||||||||
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End point title |
Percentage of participants who experienced an adverse event | ||||||||||||
End point description |
Adverse experience means any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Merck product whether or not considered related to the use of the product. Participant's parents/legal guardians recorded in the Vaccination Report Card (VRC) systemic and injection-site adverse experiences, temperatures, and any other vaccines or medications administered during Day 1 through Day 14. Analysis population: all participants who received at least 1 injection of vaccine in this study and had safety follow-up data for at least 1 day following an injection.
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End point type |
Secondary
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End point timeframe |
Up to 42 days (including follow-up 14 days post vaccination 1, 2, & 3)
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Statistical analysis title |
Difference in risk | ||||||||||||
Statistical analysis description |
Risk differences in percentage points (Modified Process Hepatitis B Vaccine - RECOMBIVAX HB™ Vaccine) and confidence intervals are based on pooled incidence rates across all study centers.
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Comparison groups |
Modified Process Hepatitis B Vaccine v RECOMBIVAX HB™ Vaccine
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Number of subjects included in analysis |
545
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
-0.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-7.8 | ||||||||||||
upper limit |
7.3 | ||||||||||||
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End point title |
Percentage of participants who discontinued from study therapy due to an adverse event | ||||||||||||
End point description |
Adverse experience means any unfavorable and unintended change in the structure (signs), function (symptoms), or chemistry (laboratory data) of the body temporally associated with any use of a Merck product whether or not considered related to the use of the product. Participant's parents/legal guardians recorded in the Vaccination Report Card (VRC) systemic and injection-site adverse experiences, temperatures, and any other vaccines or medications administered during Day 1 through Day 14. Analysis population: all participants who received at least 1 injection of vaccine in this study and had safety follow-up data for at least 1 day following an injection.
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End point type |
Secondary
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End point timeframe |
Up to 28 days (including follow-up 14 days post vaccination 1 & 2)
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Statistical analysis title |
Difference in risk | ||||||||||||
Statistical analysis description |
Risk differences in percentage points (Modified Process Hepatitis B Vaccine - RECOMBIVAX HB™ Vaccine) and confidence intervals are based on pooled incidence rates across all study centers.
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Comparison groups |
Modified Process Hepatitis B Vaccine v RECOMBIVAX HB™ Vaccine
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Number of subjects included in analysis |
545
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
Risk difference (RD) | ||||||||||||
Point estimate |
0.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1 | ||||||||||||
upper limit |
2.1 | ||||||||||||
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End point title |
Percentage of Participants with Seroprotection (anti-HBsAg >=10 mIU/mL) at Month 7 | ||||||||||||
End point description |
Seroprotection rate was measured as the percentage of participants with anti-HBsAg ≥ 10 mIU/mL at Month 7. Anti-hepatitis B surface antigen titers were measured 4 weeks after the third vaccination. Analysis population: per-protocol population included all participants who met the inclusion criteria, were not protocol violators and had serology and vaccinations within the specified day ranges.
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End point type |
Secondary
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End point timeframe |
Month 7 (1 month post vaccination 3)
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Adverse events information
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Timeframe for reporting adverse events |
Serious adverse events: Up to 7 months (entire study);
Non-serious systemic adverse events: Days 1-14 following any vaccination visit;
Non-serious injection-site adverse events: Days 1-5 following any vaccination visit
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Adverse event reporting additional description |
Population included all randomized participants who received at least 1 injection of vaccine in this study and had safety follow-up data for at least 1 day following an injection.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
RECOMBIVAX HB™ Vaccine
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Reporting group description |
RECOMBIVAX HB™ three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1 schedule. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Modified Process Hepatitis B Vaccine
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Reporting group description |
Modified Process Hepatitis B three 5 mcg dose regimen administered via intramuscular injection at birth (up to 10 days of age), 1 month after Dose 1, and 6 months after Dose 1 schedule. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Mar 2006 |
Amendment 1: protocol was amended to change the age of the participant at study entry, clarify the time of scheduled study visits, change the time the informed consent will be obtained from the parent/guardian, clarify information in the Study Flow Chart, incorporate some infant immunogenicity data into the Background and Rationale, and clarify the phosphate/aluminum content in the adjuvant. |
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14 Apr 2006 |
Amendment 2: protocol was amended to add safety evaluation committee, capture additional information on the vaccination report card, and revise study window visits, inclusion/exclusion criteria, special handling requirements, prior and concomitant medication(s)/treatment(s). |
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23 Aug 2006 |
Amendment 3: protocol was amended to change from U.S. IND. US Study to Worldwide, and revise primary Packaging and Labeling Information |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
