Papillomavirus Infections
Conditions
Brief summary
This study will evaluate the efficacy, immunogenicity, and safety of 9-valent human papillomavirus (9vHPV; V503) vaccine in Chinese men 20 to 45 years of age. It will enroll heterosexual men (HM) and men who have sex with men (MSM), will be stratified by age and sexual orientation, and will have two stages. The primary hypothesis of Stage I is: 9vHPV vaccine reduces the combined incidence of HPV 6-, 11-, 16-, 18-, 31-, 33-, 45-, 52-, and 58-related external genital and intra-anal 12-month persistent infection (PI) compared with placebo in males 20 to 45 years of age who are seronegative at Day 1 and polymerase chain reaction (PCR) negative from Day 1 through one month post-Dose 3 to the relevant HPV type. The primary hypothesis of Stages I and II combined is: 9vHPV vaccine reduces the combined incidence of HPV 6-, 11-, 16-, 18-, 31-, 33-, 45-, 52-, and 58-related genital warts, penile/perianal/perineal intraepithelial neoplasia (PIN), or penile/perianal/perineal cancer compared with placebo in males 20 to 45 years of age who are seronegative at Day 1 and PCR negative from Day 1 through one month post-Dose 3 to the relevant HPV type.
Interventions
BIOLOGICAL9vHPV Vaccine
9-valent human papillomavirus (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) L1 virus-like particle vaccine administered as a 0.5-mL IM injection
OTHERPlacebo
Sterile saline solution administered as a 0.5 mL IM injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Is a Chinese male. * Has no more than 5 lifetime sexual partners.
Exclusion criteria
* Has a history of known prior vaccination with an HPV vaccine. * Has a history of HPV-related external genital lesions, HPV-related intra-anal lesions, or HPV-related head and neck cancer. * Has a history of severe allergic reaction that required medical intervention. * Has received immune globulin or blood-derived products in the past 3 months or plans to receive any before Month 7 of the study. * Has a 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. * Has received immunosuppressive therapy in the past year, excluding inhaled, nasal, or topical corticosteroids and certain regimens of systemic corticosteroids. * Has a known thrombocytopenia or coagulation disorder that would contraindicate IM injections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage I: Combined Incidence of HPV 6-, 11-, 16-, 18-, 31-, 33-, 45-, 52-, and 58-related External Genital and Intra-anal 12-month Persistent Infection | Up to approximately 30 months | This endpoint is defined as having occurred if a participant is positive for the same HPV type by the HPV PCR assay in the penile, scrotum, perineal, perianal and intra-anal swabs, biopsy, or excised samples obtained in 3 or more consecutive visits over a period of at least 12 months. |
| Stages I and II: Combined Incidence of HPV 6-, 11-, 16-, 18-, 31-, 33-, 45-, 52-, and 58-related Genital Warts, PIN, or Penile/Perianal/Perineal Cancer | Up to approximately 78 months | This endpoint is defined as having occurred if on a single biopsy or excised tissue from a participant, there is: (a) a pathology panel consensus diagnosis of genital warts, PIN of any grade, or penile/perianal/perineal cancer; and (b) detection of at least 1 of HPV types 6, 11, 16, 18, 31, 33, 45, 52 or 58 by Thinsection PCR in an adjacent section from the same tissue block. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Percentage of Participants Achieving Seroconversion to HPV 6, 11, 16, 18, 31, 33, 45, 52, or 58 at One Month Post-Dose 3 | Month 7 | A participant who changes serostatus from seronegative at Day 1 to seropositive at one month post-Dose 3 for a given HPV type is considered to have achieved seroconversion for that type. A participant with a titer at or above the seropositivity cutoff for a given HPV type, as measured by cLIA, is considered seropositive for that type. |
| Stage I: Percentage of Participants Who Report at Least 1 Solicited Injection-site Adverse Event (AE) | Day 1 through Day 8 following any vaccination | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Solicited injection-site AEs such as erythema, swelling, pain, and induration at the injection site will be recorded. |
| Stage I: Percentage of Participants Who Report at Least 1 Solicited Systemic AE | Day 1 through Day 8 following any vaccination | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs. |
| Stage 1: Combined Incidence of HPV 6-, 11-, 16-, 18-, 31-, 33-, 45-, 52-, and 58-related External Genital and Intra-anal 6-month Persistent Infection | Up to approximately 30 months | This endpoint is defined as having occurred if a participant is positive for the same HPV type by the HPV PCR assay in the penile, scrotum, perineal, perianal and intra-anal swabs, biopsy, or excised samples obtained in 2 or more consecutive visits over a period of at least 6 months. |
| Stages I and II: Combined Incidence of HPV 6-, 11-, 16-, 18-, 31-, 33-, 45-, 52-, and 58-related Anal Intraepithelial Neoplasia (AIN) or Anal Cancer (MSM participants only) | Up to approximately 78 months | This endpoint is defined to have occurred if on a single biopsy or excised tissue from a participant, there is: (a) a pathology panel consensus diagnosis of AIN of any grade or anal cancer; and (b) detection of at least 1 of HPV types 6, 11, 16, 18, 31, 33, 45, 52 or 58 by Thinsection PCR in an adjacent section from the same tissue block. |
| Stages I and II: Percentage of Participants Who Experience at Least 1 SAE | Up to approximately 78 months | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An 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, or is another important medical event. |
| Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE) | Up to approximately 30 months | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An 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, or is another important medical event. |
| Stage 1: Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at One Month Post-Dose 3 | Month 7 | GMTs to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 will be measured with a Competitive Luminex Immunoassay (cLIA). |
Countries
China
Outcome results
None listed