Clinical Trial Results:
A Randomized, International, Double-Blinded (With In-House Blinding), Controlled With GARDASIL™, Dose-Ranging Study of Octavalent Human Papillomavirus (HPV) (Types 6, 11, 16, 18, 31, 45, 52, and 58) L1 Virus-Like Particle (VLP) Vaccine Administered to 16-23-Year-Old Women
Summary
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EudraCT number |
2017-000109-19 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
22 Aug 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Mar 2017
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First version publication date |
10 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 |
V502-001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00260039 | ||
WHO universal trial number (UTN) |
- | ||
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 |
22 Aug 2007
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Aug 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Aug 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 |
This dose-ranging study evaluated an investigational vaccine with the following objectives: (1) To demonstrate that the vaccine is well-tolerated in women (2) To evaluate immune responses in women who are between 16 and 23 years of age at enrollment. The primary hypothesis for the study are as follows: 1) the geometric mean titers (GMTs) at 4 weeks Postdose 3 for each of the Human Papillomavirus (HPV) Types 6, 11, 16, 18 for participants receiving V502 vaccination are non-inferior to those induced by qHPV vaccine (Gardasil), and 2) V502 administered to 16 to 23-year old women is generally well-tolerated.
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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 |
06 Dec 2005
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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 |
United States: 225
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Country: Number of subjects enrolled |
Peru: 150
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Country: Number of subjects enrolled |
Colombia: 305
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Worldwide total number of subjects |
680
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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) |
0
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Adolescents (12-17 years) |
16
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Adults (18-64 years) |
664
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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 female participants between 16 and 23 years of age were enrolled into the study. | |||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 738 participants were screened and 680 were randomized into the study. | |||||||||||||||||||||||||||||||||||||||||||||
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 |
Investigator, Subject | |||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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qHPV Vaccine | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received qHPV vaccine (Gardasil) 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
qHPV Vaccine
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Investigational medicinal product code |
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Other name |
Gardasil™ quadrivalent HPV (Types 6, 11, 16, 18) L1 Virus-like Particle (VLP) vaccine
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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 |
0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits
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Arm title
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Low-dose Octavalent HPV Vaccine | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received Low-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Low-dose Octavalent HPV Vaccine
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Investigational medicinal product code |
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Other name |
Low-dose Octavalent HPV (Types 6, 11, 16, 18, 31, 45, 52, 58) L1 Virus-like Particle (VLP) vaccine
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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 |
0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits
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Arm title
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Mid-dose Octavalent HPV Vaccine | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received Mid-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Mid-dose Octavalent HPV Vaccine
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Investigational medicinal product code |
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Other name |
Mid-dose Octavalent HPV (Types 6, 11, 16, 18, 31, 45, 52, 58) L1 Virus-like Particle (VLP) vaccine
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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 |
0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits
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Arm title
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High-dose Octavalent HPV Vaccine | |||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Participants received High-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
High-dose Octavalent HPV Vaccine
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Investigational medicinal product code |
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Other name |
High-dose Octavalent HPV (Types 6, 11, 16, 18, 31, 45, 52, 58) L1 Virus-like Particle (VLP) vaccine
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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 |
0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits
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Baseline characteristics reporting groups
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Reporting group title |
qHPV Vaccine
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Reporting group description |
Participants received qHPV vaccine (Gardasil) 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Low-dose Octavalent HPV Vaccine
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Reporting group description |
Participants received Low-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mid-dose Octavalent HPV Vaccine
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Reporting group description |
Participants received Mid-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
High-dose Octavalent HPV Vaccine
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Reporting group description |
Participants received High-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
qHPV Vaccine
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Reporting group description |
Participants received qHPV vaccine (Gardasil) 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | ||
Reporting group title |
Low-dose Octavalent HPV Vaccine
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Reporting group description |
Participants received Low-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | ||
Reporting group title |
Mid-dose Octavalent HPV Vaccine
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Reporting group description |
Participants received Mid-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | ||
Reporting group title |
High-dose Octavalent HPV Vaccine
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Reporting group description |
Participants received High-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. |
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End point title |
Geometric Mean Titer (GMT) of Anti-HPV 6 Antibody | ||||||||||||||||||||
End point description |
Anti-HPV Type 6 antibodies were measured by a Competitive Luminex Immunoassay (cLIA). The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and polymerase chain reaction (PCR) negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 6 antibody.
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End point type |
Primary
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End point timeframe |
Month 7 (1 month postdose 3)
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Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in GMT (experimental / control) is >0.5.
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Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
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Number of subjects included in analysis |
213
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [1] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.79
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Confidence interval |
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level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.63 | ||||||||||||||||||||
upper limit |
1 | ||||||||||||||||||||
Notes [1] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
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Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
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Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
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Number of subjects included in analysis |
216
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [2] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.9
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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 |
1.12 | ||||||||||||||||||||
Notes [2] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
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Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
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Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
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Number of subjects included in analysis |
215
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [3] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.91
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Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.72 | ||||||||||||||||||||
upper limit |
1.15 | ||||||||||||||||||||
Notes [3] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
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End point title |
GMT of Anti-HPV 11 Antibody | ||||||||||||||||||||
End point description |
Anti-HPV Type 11 antibodies were measured by a cLIA. The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL. A value of 9999 indicates that the GMT was <10 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 11 antibody.
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End point type |
Primary
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End point timeframe |
Month 7 (1 month postdose 3)
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Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
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Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
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Number of subjects included in analysis |
213
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [4] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.86
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Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.7 | ||||||||||||||||||||
upper limit |
1.05 | ||||||||||||||||||||
Notes [4] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
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Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
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Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
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Number of subjects included in analysis |
216
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [5] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.97
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Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
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lower limit |
0.8 | ||||||||||||||||||||
upper limit |
1.18 | ||||||||||||||||||||
Notes [5] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
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Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
|
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Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
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Number of subjects included in analysis |
215
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [6] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.87
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Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.69 | ||||||||||||||||||||
upper limit |
1.08 | ||||||||||||||||||||
Notes [6] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
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End point title |
GMT of Anti-HPV 16 Antibody | ||||||||||||||||||||
End point description |
Anti-HPV Type 16 antibodies were measured by a cLIA. The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 16 antibody.
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End point type |
Primary
|
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End point timeframe |
Month 7 (1 month postdose 3)
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Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
|
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Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
|
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Number of subjects included in analysis |
212
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [7] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.8
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.65 | ||||||||||||||||||||
upper limit |
0.99 | ||||||||||||||||||||
Notes [7] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
|||||||||||||||||||||
Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
219
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [8] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.91
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.74 | ||||||||||||||||||||
upper limit |
1.12 | ||||||||||||||||||||
Notes [8] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
|||||||||||||||||||||
Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
212
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [9] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.88
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.71 | ||||||||||||||||||||
upper limit |
1.09 | ||||||||||||||||||||
Notes [9] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
|
|||||||||||||||||||||
End point title |
GMT of Anti-HPV 18 Antibody | ||||||||||||||||||||
End point description |
Anti-HPV Type 18 antibodies were measured by a cLIA. The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 18 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
238
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [10] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.8
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.61 | ||||||||||||||||||||
upper limit |
1.05 | ||||||||||||||||||||
Notes [10] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
|||||||||||||||||||||
Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
246
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [11] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.83
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.64 | ||||||||||||||||||||
upper limit |
1.08 | ||||||||||||||||||||
Notes [11] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
|||||||||||||||||||||
Statistical analysis title |
Non-inferiority Analysis | ||||||||||||||||||||
Statistical analysis description |
The criterion for non-inferiority is that the lower bound of the 95% confidence interval for the fold-difference in
GMT (experimental / control) is >0.5.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
242
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
non-inferiority | ||||||||||||||||||||
P-value |
< 0.001 [12] | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Fold difference in GMT | ||||||||||||||||||||
Point estimate |
0.88
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
0.67 | ||||||||||||||||||||
upper limit |
1.16 | ||||||||||||||||||||
Notes [12] - The estimated GMT, fold difference, confidence intervals, and p-value is based on a statistical analysis model adjusting for country. |
|
|||||||||||||||||||||
End point title |
GMT of Anti-HPV 31 Antibody [13] | ||||||||||||||||||||
End point description |
Anti-HPV Type 31 antibodies were measured by a cLIA. The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 16 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 31 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [13] - 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: There was no protocol pre-planned statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
GMT of Anti-HPV 45 Antibody [14] | ||||||||||||||||||||
End point description |
Anti-HPV Type 45 antibodies were measured by a cLIA. The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 16 milli Merck U/mL. A value of 9999 indicates that the GMT was <16 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 45 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [14] - 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: There was no protocol pre-planned statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
GMT of Anti-HPV 52 Antibody [15] | ||||||||||||||||||||
End point description |
Anti-HPV Type 52 antibodies were measured by a cLIA. The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL. A value of 9999 indicates that the GMT was <20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 52 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [15] - 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: There was no protocol pre-planned statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
GMT of Anti-HPV 58 Antibody [16] | ||||||||||||||||||||
End point description |
Anti-HPV Type 58 antibodies were measured by a cLIA. The unit of measure was milli Merck Units/mL (mMU/mL). The seropositive cut-off threshold for this assay is defined as 16 milli Merck U/mL. A value of 9999 indicates that the GMT was <16 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 58 antibody .
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [16] - 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: There was no protocol pre-planned statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 6 [17] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 6 cLIA level of >=20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 6 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [17] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 11 [18] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 11 cLIA level of >=20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 11 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [18] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 16 [19] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 16 cLIA level of >=20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 16 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [19] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 18 [20] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 18 cLIA level of >=20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 18 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [20] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 31 [21] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 31 cLIA level of >=16 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 31 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [21] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 45 [22] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 45 cLIA level of >=16 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 45 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [22] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 52 [23] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 52 cLIA level of >=20 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 52 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [23] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants Who Seroconverted to HPV Type 58 [24] | ||||||||||||||||||||
End point description |
Seroconversion was defined as achieving an anti-HPV Type 58 cLIA level of >=16 milli Merck U/mL. Participants analyzed included those who were not protocol violators, received all 3 vaccinations, were seronegative at Day 1 and PCR negative from Day 1 through Month 7 for the relevant HPV Type, and had a Month 7 serum sample collected and tested for anti-HPV 58 antibody.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Month 7 (1 month postdose 3)
|
||||||||||||||||||||
Notes [24] - 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: There was no protocol pre-planned between-group statistical analysis for this endpoint. |
|||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Percentage of Participants with Maximum Oral Temperature >=37.8 °C (>=100 °F) | ||||||||||||||||||||
End point description |
Participants used the Vaccination Report Card to record oral temperature. The participants analyzed included those who received at least one vaccination and had follow-up.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Up to Day 5 after any vaccination
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method for 95% confidence intervals and a test-based normal approximation for p-values.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
337
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 0.383 | ||||||||||||||||||||
Method |
Test-based normal approximation | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-2.9
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-9.7 | ||||||||||||||||||||
upper limit |
3.7 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method for 95% confidence intervals and a test-based normal
approximation for p-values.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
335
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 0.706 | ||||||||||||||||||||
Method |
Test-based normal approximation | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
1.1
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-5 | ||||||||||||||||||||
upper limit |
7.4 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method for 95% confidence intervals and a test-based normal
approximation for p-values.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
340
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 0.905 | ||||||||||||||||||||
Method |
Test-based normal approximation | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-0.4
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-6.7 | ||||||||||||||||||||
upper limit |
6 |
|
|||||||||||||||||||||
End point title |
Percentage of Participants with One or More Injection-site Adverse Experiences | ||||||||||||||||||||
End point description |
An adverse experience (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 sponsor's product, 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 sponsor's product is also an AE. Participants used the Vaccination Report Card to record injection-site AEs. The participants analyzed included those who received at least one vaccination and had follow-up.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Up to Day 5 after any vaccination
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method for 95% confidence intervals and a test-based normal
approximation for p-values.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
337
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 0.189 | ||||||||||||||||||||
Method |
Test-based normal approximation | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-4.8
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-12.2 | ||||||||||||||||||||
upper limit |
2.4 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method for 95% confidence intervals and a test-based normal
approximation for p-values.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
335
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 0.445 | ||||||||||||||||||||
Method |
Test-based normal approximation | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-2.9
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-10.5 | ||||||||||||||||||||
upper limit |
4.7 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method for 95% confidence intervals and a test-based normal
approximation for p-values.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
340
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 0.692 | ||||||||||||||||||||
Method |
Test-based normal approximation | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-1.5
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-9.2 | ||||||||||||||||||||
upper limit |
6.1 |
|
|||||||||||||||||||||
End point title |
Percentage of Participants with One or More Systemic Adverse Experiences | ||||||||||||||||||||
End point description |
An 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 sponsor's product, 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 sponsor's product is also an AE. Percentage of participants with a systemic AE was recorded. The participants analyzed included those who received at least one vaccination and had follow-up.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Up to Day 15 after any vaccination
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method.
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
337
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-9.1
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-18.6 | ||||||||||||||||||||
upper limit |
0.6 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
335
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-2.8
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-12.7 | ||||||||||||||||||||
upper limit |
7.2 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
340
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
-4.8
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-14.6 | ||||||||||||||||||||
upper limit |
5 |
|
|||||||||||||||||||||
End point title |
Percentage of Participants with One or More Serious Vaccine-related Adverse Experiences | ||||||||||||||||||||
End point description |
A serious AE is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or is an overdose. A vaccine-related AE was deemed by the investigator to be possibly, probably, or definitely related to a study procedure. The participants analyzed included those who received at least one vaccination and had follow-up.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Up to Month 7
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
337
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 1 | ||||||||||||||||||||
Method |
Miettinen and Nurminen | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-2.2 | ||||||||||||||||||||
upper limit |
2.2 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
335
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 1 | ||||||||||||||||||||
Method |
Miettinen and Nurminen | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-2.3 | ||||||||||||||||||||
upper limit |
2.2 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
340
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
P-value |
= 1 | ||||||||||||||||||||
Method |
Miettinen and Nurminen | ||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
0
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-2.2 | ||||||||||||||||||||
upper limit |
2.2 |
|
|||||||||||||||||||||
End point title |
Percentage of Participants with One or More Severe Injection-site Adverse Experiences | ||||||||||||||||||||
End point description |
A severe AE is an AE that is deemed by the investigator to be incapacitating with inability to work or do usual activity. For injection-site erythema and injection-site swelling, severe is defined as a maximum size of >2 inches, or 5 centimeters. The participants analyzed included those who received at least one vaccination and had follow-up.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Up to Day 5 after any vaccination
|
||||||||||||||||||||
|
|||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Low-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
337
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
0.6
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-4.6 | ||||||||||||||||||||
upper limit |
6 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v Mid-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
335
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
1.2
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-4 | ||||||||||||||||||||
upper limit |
6.4 | ||||||||||||||||||||
Statistical analysis title |
Risk Difference Analysis | ||||||||||||||||||||
Statistical analysis description |
The analysis used the Miettinen and Nurminen method
|
||||||||||||||||||||
Comparison groups |
qHPV Vaccine v High-dose Octavalent HPV Vaccine
|
||||||||||||||||||||
Number of subjects included in analysis |
340
|
||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||||||
Method |
|||||||||||||||||||||
Parameter type |
Risk difference (RD) | ||||||||||||||||||||
Point estimate |
1.3
|
||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||
level |
95% | ||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||
lower limit |
-3.7 | ||||||||||||||||||||
upper limit |
6.6 |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to Month 7
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse events are reported for all participants who received at least one vaccination.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
qHPV Vaccine
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received qHPV vaccine (Gardasil) 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Low-dose Octavalent HPV Vaccine
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received Low-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Mid-dose Octavalent HPV Vaccine
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received Mid-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
High-dose Octavalent HPV Vaccine
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received High-dose Octavalent HPV Vaccine 0.5 mL intramuscular injection at the Day 1, Month 2, and Month 6 visits. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
15 Aug 2006 |
Protocol Amendment 1 changes included the following: added the U.S. IND number, revised language regarding participants who become pregnant after Day 1, clarified the definition of out-of-context study visits, clarified triage for abnormal Pap and biopsy tests obtained at Month 7, corrected the seropositivity cutoffs for HPV types, and replaced with the most recent version of the Subject Pregnancy Reporting and Follow-up Standard Operating Procedure. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |