Clinical Trial Results:
A Randomized, Double-Blinded, Tolerability and Immunogenicity Study of a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine (V504) Administered Concomitantly with GARDASIL™ to 16- to 26-Year-Old Women
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Summary
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EudraCT number |
2007-003852-13 |
Trial protocol |
SE AT DK |
Global end of trial date |
20 May 2009
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Results information
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Results version number |
v1 |
This version publication date |
16 Feb 2016
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First version publication date |
01 Apr 2015
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Other versions |
v2 |
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 |
V504-001-00
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00551187 | ||
WHO universal trial number (UTN) |
- | ||
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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, New Jersey, 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 May 2009
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 May 2009
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Global end of trial reached? |
Yes
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Global end of trial date |
20 May 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 |
1. To evaluate the tolerability of the 5-valent HPV L1 VLP vaccine when administered concomitantly with GARDASIL™ to 16- to 26-year-old women.
2. To demonstrate that administration of the 5-valent HPV L1 VLP vaccine concomitantly with GARDASIL™ (different injection sites in separate limbs) induces non-inferior Geometric Mean Titers (GMTs) for anti-HPV 6, 11, 16, and 18 compared to GARDASIL™ administered concomitantly 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 |
20 Oct 2007
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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 |
Canada: 156
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Country: Number of subjects enrolled |
United States: 146
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Country: Number of subjects enrolled |
Puerto Rico: 39
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Country: Number of subjects enrolled |
Sweden: 115
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Country: Number of subjects enrolled |
Austria: 40
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Country: Number of subjects enrolled |
Denmark: 127
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Worldwide total number of subjects |
623
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EEA total number of subjects |
282
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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) |
0
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Adolescents (12-17 years) |
72
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Adults (18-64 years) |
551
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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 |
- | |||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
The study enrolled healthy female participants 16 to 26 years old with <=4 lifetime sexual partners, no history of an abnormal Papanicolaou (Pap) test, no positive test for HPV or abnormal cervical biopsy, and no history of or baseline clinical evidence of HPV-related lesions or cancer. Other inclusion and exclusion criteria applied. | |||||||||||||||||||||||||||||||||
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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 | |||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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V504 + Gardasil™ | |||||||||||||||||||||||||||||||||
Arm description |
Participants received 0.5 mL intramuscular injections of V504 and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6 | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
V504
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Investigational medicinal product code |
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Other name |
5-Valent Human Papillomavirus (HPV) L1 Virus-like Particle (VLP) Vaccine (HPV Types 31, 33, 45, 52, 58)
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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 |
Participants received 0.5 mL intramuscular injections (deltoid muscle of the non-dominant limb preferred) on Day 1, Month 2, and Month 6
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Investigational medicinal product name |
Gardasil™
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Investigational medicinal product code |
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Other name |
4-Valent Human Papillomavirus (HPV) L1 Virus-like Particle (VLP) Vaccine (HPV Types 6, 11, 16, 18); Gardasil™, Silgard™
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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 |
Participants received 0.5 mL intramuscular injections (deltoid muscle of the dominant limb preferred) on Day 1, Month 2, and Month 6
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Arm title
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Placebo + Gardasil™ | |||||||||||||||||||||||||||||||||
Arm description |
Participants received 0.5 mL intramuscular injections of placebo and Gardasil™ in separate limbs on 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 |
Placebo for V504
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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 |
Participants received 0.5 mL intramuscular injections (deltoid muscle of the non-dominant limb preferred) on Day 1, Month 2, and Month 6
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Investigational medicinal product name |
Gardasil™
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Investigational medicinal product code |
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Other name |
4-Valent Human Papillomavirus (HPV) L1 Virus-like Particle (VLP) Vaccine (HPV Types 6, 11, 16, 18); Gardasil™, Silgard™
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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 |
Participants received 0.5 mL intramuscular injections (deltoid muscle of the dominant limb preferred) on Day 1, Month 2, and Month 6
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Baseline characteristics reporting groups
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Reporting group title |
V504 + Gardasil™
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Reporting group description |
Participants received 0.5 mL intramuscular injections of V504 and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + Gardasil™
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Reporting group description |
Participants received 0.5 mL intramuscular injections of placebo and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
V504 + Gardasil™
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Reporting group description |
Participants received 0.5 mL intramuscular injections of V504 and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6 | ||
Reporting group title |
Placebo + Gardasil™
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Reporting group description |
Participants received 0.5 mL intramuscular injections of placebo and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6 | ||
Subject analysis set title |
V504 + Gardasil™ - Safety Analysis
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received 0.5 mL intramuscular injections of V504 and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6. The analysis set includes participants who received >=1 vaccination and had safety follow-up.
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Subject analysis set title |
Placebo + Gardasil™ - Safety Analysis
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Participants received 0.5 mL intramuscular injections of Placebo and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6. The analysis set includes participants who received >=1 vaccination and had safety follow-up.
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End point title |
Geometric Mean Titers (GMTs) to the HPV Types Contained in the Study Vaccines | |||||||||||||||||||||||||||||||||||||||
End point description |
Serum antibodies to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were measured using a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. Titers given as zero (0) were reported as 'less than' values; these were <4 milli Merck Units/mL for Type 33 and Type 45, <2 milli Merck Units/mL for Type 52, and <3 milli Merck Units/mL for Type 58. Statistical analysis includes only HPV types contained in the Gardasil™ vaccine.
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End point type |
Primary
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End point timeframe |
Four weeks post vaccination 3 (Month 7)
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| Notes [1] - Had 3 doses, Month 7 results, and negative results to ≥1 HPV type by PCR and serology up to Month 7 [2] - Had 3 doses, Month 7 results, and negative results to ≥1 HPV type by PCR and serology up to Month 7 |
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Statistical analysis title |
Non-inferiority Anti-HPV Type 6 | |||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Primary analysis evaluated non-inferiority of the GMT for anti-HPV Type 6 in participants who received V504 + Gardasil™ compared with those who received placebo + Gardasil™
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Comparison groups |
Placebo + Gardasil™ v V504 + Gardasil™
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Number of subjects included in analysis |
497
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | |||||||||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||||||||
Method |
ANOVA | |||||||||||||||||||||||||||||||||||||||
Parameter type |
GMT Ratio | |||||||||||||||||||||||||||||||||||||||
Point estimate |
0.87
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.74 | |||||||||||||||||||||||||||||||||||||||
upper limit |
1.02 | |||||||||||||||||||||||||||||||||||||||
| Notes [3] - Criterion for non-inferiority with respect to the GMT ratio (V504 + Gardasil™ / placebo + Gardasil™) requires that the lower bound of the 95% confidence interval be >0.5 to rule out a decrease of 2-fold or more. An analysis of variance model with a response of log individual titers and a fixed effect for group was used. |
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Statistical analysis title |
Non-inferiority Anti-HPV Type 11 | |||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Primary analysis evaluated non-inferiority of the GMT for anti-HPV Type 11 in participants who received V504 + Gardasil™ compared with those who received placebo + Gardasil™
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Comparison groups |
V504 + Gardasil™ v Placebo + Gardasil™
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Number of subjects included in analysis |
497
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [4] | |||||||||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||||||||
Method |
ANOVA | |||||||||||||||||||||||||||||||||||||||
Parameter type |
GMT Ratio | |||||||||||||||||||||||||||||||||||||||
Point estimate |
0.86
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.73 | |||||||||||||||||||||||||||||||||||||||
upper limit |
1.01 | |||||||||||||||||||||||||||||||||||||||
| Notes [4] - Criterion for non-inferiority with respect to the GMT ratio (V504 + Gardasil™ / placebo + Gardasil™) requires that the lower bound of the 95% confidence interval be >0.5 to rule out a decrease of 2-fold or more. An analysis of variance model with a response of log individual titers and a fixed effect for group was used. |
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Statistical analysis title |
Non-inferiority Anti-HPV Type 16 | |||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Primary analysis evaluated non-inferiority of the GMT for anti-HPV Type 16 in participants who received V504 + Gardasil™ compared with those who received placebo + Gardasil™
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Comparison groups |
V504 + Gardasil™ v Placebo + Gardasil™
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Number of subjects included in analysis |
497
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [5] | |||||||||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||||||||
Method |
ANOVA | |||||||||||||||||||||||||||||||||||||||
Parameter type |
GMT Ratio | |||||||||||||||||||||||||||||||||||||||
Point estimate |
0.87
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.75 | |||||||||||||||||||||||||||||||||||||||
upper limit |
1.01 | |||||||||||||||||||||||||||||||||||||||
| Notes [5] - Criterion for non-inferiority with respect to the GMT ratio (V504 + Gardasil™ / placebo + Gardasil™) requires that the lower bound of the 95% confidence interval be >0.5 to rule out a decrease of 2-fold or more. An analysis of variance model with a response of log individual titers and a fixed effect for group was used. |
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Statistical analysis title |
Non-inferiority Anti-HPV Type 18 | |||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Primary analysis evaluated non-inferiority of the GMT for anti-HPV Type 18 in participants who received V504 + Gardasil™ compared with those who received placebo + Gardasil™
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Comparison groups |
V504 + Gardasil™ v Placebo + Gardasil™
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Number of subjects included in analysis |
497
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [6] | |||||||||||||||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||||||||||||||
Method |
ANOVA | |||||||||||||||||||||||||||||||||||||||
Parameter type |
GMT Ratio | |||||||||||||||||||||||||||||||||||||||
Point estimate |
0.98
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Confidence interval |
||||||||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.79 | |||||||||||||||||||||||||||||||||||||||
upper limit |
1.21 | |||||||||||||||||||||||||||||||||||||||
| Notes [6] - Criterion for non-inferiority with respect to the GMT ratio (V504 + Gardasil™ / placebo + Gardasil™) requires that the lower bound of the 95% confidence interval be >0.5 to rule out a decrease of 2-fold or more. An analysis of variance model with a response of log individual titers and a fixed effect for group was used. |
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End point title |
Number of Participants with an Adverse Event [7] | |||||||||
End point description |
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
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End point type |
Primary
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End point timeframe |
Up to 7 weeks after vaccination 3 (up to 31 weeks)
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was conducted for Number of Participants with an Adverse Event |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants Discontinued from Study Vaccine Due to an Adverse Event [8] | |||||||||
End point description |
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
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End point type |
Primary
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End point timeframe |
Up to Month 6
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was conducted for Number of Participants Discontinued from Study Vaccine Due to an Adverse Event |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants with a Vaccine-Related Adverse Event [9] | |||||||||
End point description |
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. An AE that is judged by the Investigator to be “definitely related,” “probably related,” or “possibly related” is defined as a vaccine-related.
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End point type |
Primary
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End point timeframe |
Up to 7 weeks after vaccination 3 (up to 31 weeks)
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was performed for Number of Participants with a Vaccine-Related Adverse Event |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants with one or more Injection-site Adverse Events Prompted on the Vaccination Report Card | ||||||||||||||||||
End point description |
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Specific injection-site AEs, such as erythema, pain, and swelling, were prompted for on the Vaccination Report Card.
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End point type |
Primary
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End point timeframe |
Up to 5 days after any vaccination
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| Notes [10] - Participants in the Safety Analysis who had Vaccination Report Card results [11] - Participants in the Safety Analysis who had Vaccination Report Card results |
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Statistical analysis title |
Injection-site Erythema AEs | ||||||||||||||||||
Statistical analysis description |
The incidence of VRC-prompted injection-site erythema was compared between the treatment groups. Injection-site erythema AEs on both injection sites were included in the analysis.
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Comparison groups |
V504 + Gardasil™ - Safety Analysis v Placebo + Gardasil™ - Safety Analysis
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Number of subjects included in analysis |
609
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.083 | ||||||||||||||||||
Method |
Miettinen & Nurminen | ||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||
Point estimate |
6.6
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-0.9 | ||||||||||||||||||
upper limit |
14 | ||||||||||||||||||
Statistical analysis title |
Injection-site Pain AEs | ||||||||||||||||||
Statistical analysis description |
The incidence of VRC-prompted injection-site pain was compared between the treatment groups. Injection-site pain AEs on both injection sites were included in the analysis.
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Comparison groups |
V504 + Gardasil™ - Safety Analysis v Placebo + Gardasil™ - Safety Analysis
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Number of subjects included in analysis |
609
|
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Analysis specification |
Pre-specified
|
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.284 | ||||||||||||||||||
Method |
Miettinen & Nurminen | ||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||
Point estimate |
2.7
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2.3 | ||||||||||||||||||
upper limit |
7.9 | ||||||||||||||||||
Statistical analysis title |
Injection-site Swelling AEs | ||||||||||||||||||
Statistical analysis description |
The incidence of VRC-prompted injection-site swelling was compared between the treatment groups. Injection-site swelling AEs on both injection sites were included in the analysis.
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Comparison groups |
V504 + Gardasil™ - Safety Analysis v Placebo + Gardasil™ - Safety Analysis
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Number of subjects included in analysis |
609
|
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Analysis specification |
Pre-specified
|
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Analysis type |
other | ||||||||||||||||||
P-value |
= 0.045 | ||||||||||||||||||
Method |
Miettinen & Nurminen | ||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||
Point estimate |
7.6
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
|
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lower limit |
0.2 | ||||||||||||||||||
upper limit |
14.9 | ||||||||||||||||||
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End point title |
Number of Participants with Elevated Body Temperature (>=37.8° C, >=100° F) | |||||||||
End point description |
Participants were instructed by the investigator to use the Vaccine Report Card to document evening oral temperature daily after each study vaccination
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End point type |
Primary
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End point timeframe |
Up to 5 days after any vaccination
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| Notes [12] - Participants in the Safety Analysis who had temperature results [13] - Participants in the Safety Analysis who had temperature results |
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Statistical analysis title |
Elevated Body Temperature | |||||||||
Statistical analysis description |
The incidence of maximum body temperature >=37.8° C reported on the Vaccine Report Card was compared between the treatment groups
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Comparison groups |
V504 + Gardasil™ - Safety Analysis v Placebo + Gardasil™ - Safety Analysis
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Number of subjects included in analysis |
614
|
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Analysis specification |
Pre-specified
|
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Analysis type |
other | |||||||||
P-value |
= 0.183 | |||||||||
Method |
Miettinen & Nurminen | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
2
|
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Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
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lower limit |
-1 | |||||||||
upper limit |
5.3 | |||||||||
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End point title |
Percentage of Participants with Seroconversion to the HPV Types Contained in the Study Vaccines | |||||||||||||||||||||||||||||||||||||||
End point description |
Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥20; HPV Type 11: ≥16; HPV Type 16: ≥20; HPV Type 18: ≥24; HPV Type 31: ≥10; HPV Types 33, 45, 52, and 58: ≥8. For the V504 + Gardasil™ arm, the criterion for acceptability of the seroconversion percentage for HPV Types 31, 33, 45, 52, and 58 required that the lower bound of the 2-sided 95% confidence interval be >90%.
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End point type |
Secondary
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End point timeframe |
Four weeks post vaccination 3 (Month 7)
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| Notes [14] - Had 3 doses, Month 7 results, and negative results to ≥1 HPV type by PCR and serology up to Month 7 [15] - Had 3 doses, Month 7 results, and negative results to ≥1 HPV type by PCR and serology up to Month 7 |
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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 |
Serious adverse events: up to Month 7; Non-serious adverse events: up to 15 days after any vaccination.
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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 |
12.1
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Reporting groups
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Reporting group title |
V504 + Gardasil™
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Reporting group description |
Participants received 0.5 mL intramuscular injections of V504 and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo + Gardasil™
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Reporting group description |
Participants received 0.5 mL intramuscular injections of placebo and Gardasil™ in separate limbs on Day 1, Month 2, and Month 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? 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 | |||
