Clinical Trial Results:
A Phase II Double-Blind Comparative Study of V501 in Females Aged 9 to 17 Years
Summary
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EudraCT number |
2017-000112-42 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
18 Sep 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Mar 2017
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First version publication date |
25 Mar 2017
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Other versions |
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 |
V501-028
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00411749 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Merck Study Number: 2006_052 | ||
Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, 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 |
18 Sep 2009
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Sep 2009
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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 |
To evaluate the serum antibody titers to the vaccine human papilloma virus (HPV) types at 1 month Postdose 3 in the participants who received the quadrivalent HPV (Types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine compared with placebo.
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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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Dec 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Japan: 107
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Worldwide total number of subjects |
107
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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) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
37
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Adolescents (12-17 years) |
70
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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 |
Study was conducted at 8 sites in Japan from 2006 to 2009. | |||||||||
Pre-assignment
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Screening details |
Girls between the ages of 9 years and 17 years who had not yet had coitarche and did not plan on becoming sexually active through the course of the study were enrolled in Part I. Participants randomly assigned to receive V501 and received all 3 vaccination in Part I were followed for an additional 2 years. | |||||||||
Period 1
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Period 1 title |
Treatment - Day 1 to Month 7
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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 | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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V501 | |||||||||
Arm description |
Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Vaccine. Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Vaccine
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Investigational medicinal product code |
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Other name |
Gardasil
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6).
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Arm title
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Placebo | |||||||||
Arm description |
Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6).
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Period 2
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Period 2 title |
Follow-up
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Is this the baseline period? |
No | |||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||
Arms
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Arm title
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V501 | |||||||||
Arm description |
Participants who received V501 in treatment period and were followed for 2 years after last vaccination | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Only participants from V501 arm were enrolled in follow-up. Participants from placebo arm did not continue. |
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Baseline characteristics reporting groups
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Reporting group title |
V501
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Reporting group description |
Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Vaccine. Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
V501
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Reporting group description |
Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Vaccine. Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | ||
Reporting group title |
Placebo
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Reporting group description |
Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | ||
Reporting group title |
V501
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Reporting group description |
Participants who received V501 in treatment period and were followed for 2 years after last vaccination | ||
Subject analysis set title |
V501- Part I
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants who received 3 doses of Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (V501) and who were not general protocol violators, received all 3 vaccinations within acceptable day ranges, were seronegative at Day 1 for the relevant HPV type, and a Month 7 serum sample collected within an acceptable time range.
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Subject analysis set title |
Placebo - Part I
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants who received 3 doses of placebo and who were not general protocol violators, received all 3 vaccinations within acceptable day ranges, were seronegative at Day 1 for the relevant HPV type, and a Month 7 serum sample collected within an acceptable time range.
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Subject analysis set title |
V501- Part II
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Participants who received all 3 doses of V501 in Part I and were followed from Month 7 to Month 31 (24 months post last dose of V501) and had available data for endpoint
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End point title |
Human Papilloma Virus (HPV) 6 Serum Antibody Titer at Month 7 | ||||||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 6 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 7 mMU/ml. Geometric mean titers (GMTs) and confidence limits below the limit of detection are shown as "7.0".
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End point type |
Primary
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End point timeframe |
Month 7 (1 month after last vaccination)
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Notes [1] - Data not available for 2 participants |
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Statistical analysis title |
Between Group Comparison | ||||||||||||
Comparison groups |
V501- Part I v Placebo - Part I
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Number of subjects included in analysis |
105
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Human Papilloma Virus (HPV) 11 Serum Antibody Titer at Month 7 | ||||||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 11 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 8 mMU/ml. Geometric mean titers (GMTs) and confidence limits below the limit of detection are shown as "8.0".
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End point type |
Primary
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End point timeframe |
Month 7 (1 month after last vaccination)
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Notes [2] - Data not available for 2 participants |
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Statistical analysis title |
Between Group Comparison | ||||||||||||
Comparison groups |
V501- Part I v Placebo - Part I
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Number of subjects included in analysis |
105
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Human Papilloma Virus (HPV) 16 Serum Antibody Titer at Month 7 | ||||||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 16 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 11 mMU/ml. Geometric mean titers (GMTs) and confidence limits below the limit of detection are shown as "11.0".
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End point type |
Primary
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End point timeframe |
Month 7 (1 month after last vaccination)
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Statistical analysis title |
Between Group Comparison | ||||||||||||
Comparison groups |
V501- Part I v Placebo - Part I
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Human Papilloma Virus (HPV) 18 Serum Antibody Titer at Month 7 | ||||||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 10 mMU/ml. Geometric mean titers (GMTs) and confidence limits below the limit of detection are shown as "10.0".
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End point type |
Primary
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End point timeframe |
Month 7 (1 month after last vaccination)
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Statistical analysis title |
Between Group Comparison | ||||||||||||
Comparison groups |
V501- Part I v Placebo - Part I
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Number of subjects included in analysis |
107
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
Human Papilloma Virus (HPV) 6 Serum Antibody Titer at Month 30 | ||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 6 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 7 mMU/ml.
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End point type |
Secondary
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End point timeframe |
Month 30 (24 months post last dose of vaccine)
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Notes [3] - Data not available for 3 participants |
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No statistical analyses for this end point |
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End point title |
Human Papilloma Virus (HPV) 11 Serum Antibody Titer at Month 30 | ||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 11 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 8 mMU/ml.
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End point type |
Secondary
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End point timeframe |
Month 30 (24 months post last dose of vaccine)
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Notes [4] - Data not available for 2 participants |
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No statistical analyses for this end point |
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End point title |
Human Papilloma Virus (HPV) 16 Serum Antibody Titer at Month 30 | ||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 16 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 11 mMU/ml.
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End point type |
Secondary
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End point timeframe |
Month 30 (24 months post last dose of vaccine)
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No statistical analyses for this end point |
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End point title |
Human Papilloma Virus (HPV) 18 Serum Antibody Titer at Month 30 | ||||||||
End point description |
Antibodies to HPV virus-like particles (VLP) type 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The limit of detection of the assay was 10 mMU/ml.
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End point type |
Secondary
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End point timeframe |
Month 30 (24 months post last dose of vaccine)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 14 days post each of the 3 vaccinations for non-serious adverse events. Serious adverse events were collected during the entire study.
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Adverse event reporting additional description |
Population included all enrolled participants who received at least 1 injection and had available safety data.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.0
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Reporting groups
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Reporting group title |
V501
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Reporting group description |
Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Vaccine. Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Total of three 0.5 mL intramuscular injections (Day 1, Month 2, and Month 6). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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 |