Efficacy and Tolerability Study of V501 in Japanese Males (V501-122)

• ClinicalTrials.gov Identifier: NCT01862874
• Recruitment Status: Completed
• First Posted: May 27, 2013
• Results First Posted: August 31, 2018
• Last Update Posted: April 2, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

A study to evaluate the efficacy and tolerability of V501 (quadrivalent Human Papilloma Virus [HPV] [Type 6, 11, 16 and 18] L1 Virus-Like Particle vaccine, GARDASIL™) in healthy, 16- to 26-year old Japanese males. The hypotheses tested are: 1) V501 reduces the combined incidence of HPV 6-, 11-, 16-, or 18-related persistent infection compared with placebo, and 2) V501 reduces the combined incidence of HPV 6-, 11-, 16-, or 18-related persistent infection, condyloma acuminata, penile/perianal/perineal intraepithelial neoplasia, or penile, perianal, or perineal cancer compared with placebo.

Condition or disease	Intervention/treatment	Phase
Anogenital Human Papilloma Virus Infection; Condyloma Acuminata	Biological: V501; Biological: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase III Placebo-controlled Clinical Trial to Study the Tolerability, Immunogenicity and Efficacy of V501 in 16- to 26-year-old Japanese Men
• Actual Study Start Date: June 27, 2013
• Actual Primary Completion Date: August 30, 2017
• Actual Study Completion Date: August 30, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: V501; Participants received V501 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Biological: V501; Formulated with aluminum hydroxyphosphate sulfate (AAHS) adjuvant; Other Names: GARDASIL™; Quadrivalent HPV (Type 6, 11, 16 and 18) L1 Virus-Like Particle vaccine
Placebo Comparator: Placebo; Participants received placebo 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6. Follow-up was up to Month 36.	Biological: Placebo; Formulated with AAHS adjuvant

Outcome Measures

Primary Outcome Measures :

1. Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection [ Time Frame: Up to Month 36 ]
   Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed.
2. Percentage of Participants With Maximum Temperature ≥37.5°C Reported on the Vaccination Report Card [ Time Frame: Up to 5 days after any vaccination ]
   Body temperature (oral or oral equivalent) was recorded on the Vaccination Report Card (VRC). The percentage of participants with a maximum temperature ≥37.5°C was summarized.
3. Percentage of Participants With an Injection-site Adverse Event Prompted on the Vaccination Report Card [ Time Frame: Up to 5 days after any vaccination ]
   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 percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, and swelling) was summarized.
4. Percentage of Participants With a Systemic Adverse Event [ Time Frame: Up to 15 days after any vaccination ]
   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 percentage of participants with a systemic AE was summarized.
5. Percentage of Participants With a Vaccine-related Systemic Adverse Event [ Time Frame: Up to 15 days after any vaccination ]
   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. Vaccine-related AEs are those that were deemed possibly, probably, or definitely related to vaccine administration by the investigator. The percentage of participants with a vaccine-related systemic AE was summarized.

Secondary Outcome Measures :

1. Combined Incidence of HPV Type 6, 11, 16, or 18-related Persistent Infection or Disease [ Time Frame: Up to Month 36 ]
   Persistent infection was defined as 1) polymerase chain reaction (PCR) positive to HPV Type 6, 11, 16, or 18 in 2 consecutive anogenital or biopsy samples collected ≥4 months apart, or 2) Pathology Panel consensus diagnosis of condyloma acuminate, penile/perianal/perineal intraepithelial neoplasia (PIN), penile, perianal, or perineal cancer and PCR detection of HPV Type 6, 11, 16, or 18 in an adjacent section and PCR positive for the same HPV type at a separate adjacent visit. The incidence of persistent infection detected in samples from ≥2 consecutive visits ≥6 months apart was assessed. Disease was defined as HPV Type 6, 11, 16, or 18-related condyloma acuminate, PIN, penile, perianal, or perineal cancer. The combined incidence of HPV Type 6, 11, 16, or 18 persistent infection or disease was assessed.

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 26 Years (Child, Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Japanese
• No clinical evidence of gross genital lesion suggesting sexually-transmitted disease and no clinically present external genital warts
• Other inclusion criteria will be discussed with the investigator during screening

Exclusion Criteria:

• History of known prior vaccination with an HPV vaccine or plans to receive one outside the study
• History of external genital warts
• History of severe allergic reaction that required medical intervention
• Received immune globulin or blood-derived products in the past 6 months or plan to receive any before Month 7 of the study
• History of splenectomy, is currently immunocompromised, or has been diagnosed with immunodeficiency, Human Immunodeficiency Virus (HIV), lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition
• Received immunosuppressive therapy in the past year, excluding inhaled, nasal, or topical corticosteroids and certain regimens of systemic corticosteroids
• Known thrombocytopenia or coagulation disorder that would contraindicate intramuscular injections
• Ongoing alcohol or drug abuse within the past 12 months

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:

Study Protocol and Statistical Analysis Plan  [PDF] April 4, 2013

More Information

Publications of Results:

Mikamo H, Yamagishi Y, Murata S, Yokokawa R, Han SR, Wakana A, Sawata M, Tanaka Y. Efficacy, safety, and immunogenicity of a quadrivalent HPV vaccine in Japanese men: A randomized, Phase 3, placebo-controlled study. Vaccine. 2019 Mar 14;37(12):1651-1658. doi: 10.1016/j.vaccine.2019.01.069. Epub 2019 Feb 20.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01862874
• Other Study ID Numbers: V501-122; 132237 ( Registry Identifier: JAPIC-CTI ); 2015-002931-16 ( EudraCT Number ); V501-122 ( Other Identifier: Merck Protocol Number )
• First Posted: May 27, 2013
• Results First Posted: August 31, 2018
• Last Update Posted: April 2, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Papillomavirus Infections; Papilloma; Virus Diseases; Neoplasms, Squamous Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; DNA Virus Infections; Tumor Virus Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs