Clinical Trial Results:
A Phase III, Open-Label, Clinical Trial to Study the Safety and Immunogenicity of the Quadrivalent HPV (Types 6, 11, 16, 18) L1 VLP Particle (VLP) Vaccine in 9- to 15-Year- Old Japanese Boys
|
Summary
|
|
EudraCT number |
2015-004212-37 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
08 Aug 2018
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
16 Mar 2019
|
First version publication date |
16 Mar 2019
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
V501-200
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02576054 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Merck Sharp & Dohme Corp.
|
||
Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
|
||
Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
08 Aug 2018
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
08 Aug 2018
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of the study is to demonstrate that administration of V501 induces high seroconversion rates for the vaccine HPV types (6, 11, 16 and 18) at 4 weeks post dose 3 in 9- to 15- year-old Japanese boys.
|
||
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.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
20 Nov 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Japan: 101
|
||
Worldwide total number of subjects |
101
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
36
|
||
Adolescents (12-17 years) |
65
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||||||||||||
|
Recruitment
|
|||||||||||||||||
Recruitment details |
- | ||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||
Screening details |
Healthy Japanese male participants between the ages of 9 and 15 years (inclusive) were enrolled in the study. Additional inclusion/exclusion criteria applied. | ||||||||||||||||
|
Period 1
|
|||||||||||||||||
Period 1 title |
Vaccination Period
|
||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||
|
Arms
|
|||||||||||||||||
|
Arm title
|
V501 | ||||||||||||||||
Arm description |
V501 administered as a 0.5 mL intramuscular injection at Day 1, Month 2 and Month 6. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Quadrivalent HPV (Type 6, 11, 16 and 18) L1 Virus-Like Particle (VLP) vaccine
|
||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||
Other name |
|||||||||||||||||
Pharmaceutical forms |
Suspension for injection
|
||||||||||||||||
Routes of administration |
Intramuscular use
|
||||||||||||||||
Dosage and administration details |
Administered as a 0.5 mL intramuscular injection at Day 1, Month 2 and Month 6.
|
||||||||||||||||
|
|||||||||||||||||
|
Period 2
|
|||||||||||||||||
Period 2 title |
Follow-up Period
|
||||||||||||||||
Is this the baseline period? |
No | ||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||
|
Arms
|
|||||||||||||||||
|
Arm title
|
V501 | ||||||||||||||||
Arm description |
Participants that completed Period 1 of the study. | ||||||||||||||||
Arm type |
No intervention | ||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
||||||||||||||||
|
|||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
V501
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
V501 administered as a 0.5 mL intramuscular injection at Day 1, Month 2 and Month 6. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
V501
|
||
Reporting group description |
V501 administered as a 0.5 mL intramuscular injection at Day 1, Month 2 and Month 6. | ||
Reporting group title |
V501
|
||
Reporting group description |
Participants that completed Period 1 of the study. | ||
Subject analysis set title |
V501-Efficacy
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All participants that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 7 serology result within 21 to 49 days post dose 3.
|
||
Subject analysis set title |
V501-Safety
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants who received at least 1 study vaccination and had follow-up safety data.
|
||
Subject analysis set title |
Participants Aged 9 to 15 years (PN 200)-Efficacy
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All participants aged 9 to 15 years of age that received all 3 vaccinations within acceptable day ranges, were seronegative to the relevant HPV type at day 1, did not have protocol violations that could interfere with evaluation of the immune response, and provided Month 7 serology result within 21 to 49 days post dose 3.
|
||
|
|||||||||||||||||
End point title |
Percentage of Participants with Seroconversion for HPV Types 6, 11, 16, and 18 [1] | ||||||||||||||||
End point description |
Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive Luminex immunoassay 4 weeks after 3rd vaccination (Month 7). Antibody titers were expressed as milli Merck units/mL (mMU/mL). Seroconversion was defined as an anti-HPV 6 titer ≥20 milliMerck units per milliliter (mMU/mL, an anti-HPV 11 titer ≥16 mMU/mL, an anti-HPV 16 titer of ≥20 mMU/mL and an anti-HPV 18 titer of ≥24 mMU/mL.
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Four weeks postdose 3 (Month 7)
|
||||||||||||||||
| Notes [1] - 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 planned for this endpoint. |
|||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||
End point title |
Percentage of Participants with Elevated Oral Temperature (≥37.5° C) [2] | ||||||||||||||
End point description |
The parent/guardian of the participant was to record the participant’s oral temperature in the evening after each study vaccination and daily for 4 days after each study vaccination. Elevated temperature was defined as ≥99.5°F (≥37.5ºC). The percentage of participants that had an elevated temperature was summarized.
|
||||||||||||||
End point type |
Primary
|
||||||||||||||
End point timeframe |
Up to Day 5 after any vaccination
|
||||||||||||||
| Notes [2] - 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 planned for this endpoint. |
|||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||
End point title |
Percentage of Participants with an Injection-site Adverse Event [3] | ||||||||
End point description |
An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. The parent/guardian of the participant was to record the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 5 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to Day 5 after any vaccination
|
||||||||
| Notes [3] - 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 planned for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants with a Systemic Adverse Event [4] | ||||||||
End point description |
An adverse event (AE) is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study drug. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug or a protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study drug or protocol-specified procedure is also an AE. The parent/guardian of the participant was to record the presence of any VRC-prompted systemic AEs that occurred in the 5 days after any vaccination The percentage of participants with a systemic AE was summarized.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to Day 15 after any vaccination
|
||||||||
| Notes [4] - 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 planned for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants with a Serious Adverse Event [5] | ||||||||
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. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs were summarized.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to Day 15 after any vaccination
|
||||||||
| Notes [5] - 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 planned for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Participants with a Vaccine-related Serious Adverse Event [6] | ||||||||
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. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, is a cancer, is an overdose, or is another important medical event. The percentage of participants that experienced 1 or more SAEs that were considered at least possibly related to the study vaccine were summarized.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Up to 30 months
|
||||||||
| Notes [6] - 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 planned for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||
End point title |
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18 at Month 7 | ||||||||||||||||
End point description |
Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). GMTs obtained for each anti-HPV from this study were compared to each of the ant-HPV GMTs obtained in study V501-122 (NCT NCT01862874) in which Japanese males 16 to 26 years received V501 in the same 3 dose regimen, to test a hypothesis that would demonstrate non-inferiority. Due to limitations in EudraCT data entry system, these comparisons cannot be included in the record. The comparisons can be viewed at https://clinicaltrials.gov/ (NCT02576054).
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Four weeks postdose 3 (Month 7)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at Month 18 | ||||||||||||||||
End point description |
Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
12 months postdose 3 (Mouth 18)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Geometric Mean Titers for Serum Anti-HPV Types 6, 11, 16, and 18: Persistence at Month 30 | ||||||||||||||||
End point description |
Antibodies to HPV Types 6, 11, 16, and 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL).
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
24 months postdose 3 (Month 30)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants with Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at Month 18 | ||||||||||||||||
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
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
12 months postdose 3 (Month 18)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||
End point title |
Percentage of Participants with Seroconversion for HPV Types 6, 11, 16, and 18: Persistence at Month 30 | ||||||||||||||||
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
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
24 months postdose 3 (Month 30)
|
||||||||||||||||
|
|||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 30 months
|
||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety population included all participants that received at least 1 vaccination.
|
||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
V501
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
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 | |||
