Clinical trial NCT03998254: Efficacy, Immunogenicity and Safety of V503 in Chinese Women Aged 20-45 Years (V503-023)
Official title: A Phase 3 Randomized, Double-Blinded, Controlled With GARDASIL® Efficacy, Immunogenicity and Safety Study of V503 [a 9-Valent HPV Vaccine] in Chinese Women 20 to 45 Years of Age
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Papillomavirus Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-06-26
Enrollment: 6000
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate the efficacy, immunogenicity and safety of 9-valent human papillomavirus (9vHPV; V503) vaccine in Chinese women 20 to 45 years of age. The primary hypotheses are: 9vHPV vaccine reduces the incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month persistent infection at least 1 month post Dose 3, compared with quadrivalent HPV (qHPV) vaccine in women 20 to 45 years of age who are seronegative at Day 1 and polymerase chain reaction (PCR) negative Day 1 through Month 7 to the relevant HPV type; and 9vHPV vaccine induces non-inferior competitive luminex immunoassay (cLIA) geometric mean titers (GMTs) for each of HPV 6, 11, 16, and 18 one month post Dose 3, compared with qHPV vaccine in women 20 to 45 years of age who are seronegative at Day 1 and PCR negative Day 1 through Month 7 to the relevant HPV type.

Detailed description: This study has two stages with the Stage I expected from Day 1 through Month 30, and the Stage II expected post-Month 30 to Month 90. The Stage I study is a case-driven study which aims to accrue at least 20 cases of HPV 31/33/45/52/58-related 12-month persistent infection and at least 39 cases of HPV 31/33/45/52/58-related 6-month persistent infection by completion of Month 30 visit. The Stage II study is a case-driven study which aims to accrue at least 12 cases of HPV 31/33/45/52/58-related cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3), cervical adenocarcinoma in situ (AIS), and cervical cancer observed in both Stage I and Stage II, by completion of Month 90 visit.

Eligibility criteria: Inclusion Criteria

* Healthy
* Has not had sex with males or has had sex with males and used effective contraception with no failures since the first day of the participant's last menstrual period through Day 1
* Agrees to use effective contraception if has sex with a male partner during study
* Has had sexual intercourse with male partners, and has had 1 to 4 male and/or female sexual partners

Exclusion Criteria

* History of a positive test for HPV
* History of an abnormal Pap test result showing ASC-US, atypical squamous cells - cannot exclude HSIL (high grade squamous intraepithelial lesion \[(ASC-H)\], low-grade squamous intraepithelial lesion (LSIL), HSIL), or atypical glandular cells
* History of an abnormal cervical biopsy result showing CIN, adenocarcinoma in situ or cervical cancer
* History of or clinical evidence at the Day 1 gynecologic examination of HPV-related anogenital diseases (e.g., genital warts, VIN, VaIN, AIN, vulvular cancer, vaginal cancer or anal cancer
* Does not have an intact cervix uteri or has more than one cervix uteri
* Is pregnant
* Known allergy to any vaccine component, including aluminum, yeast, or Benzonase™ (nuclease, Nycomed™ \[used to remove residual nucleic acids from this and other vaccines\])
* History of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension or shock) that required medical intervention
* Has thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections
* Currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition
* Has had a splenectomy
* Is expecting to donate eggs during Day 1 through Month 7 of the study
* Plans to receive during Day 1 through Month 7 of the study, is receiving or has received within 12 months prior to enrollment the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (Arava™), tumor necrosis factor (TNF)-α antagonists, monocolonal antibody therapies (including rituximab \[Rituxan™\]), intravenous gamma globulin (IVIG), antilymphocyte sera, or other therapy known to interfere with the immune response. With regard to systemic corticosteroids, a participant will be excluded if she is currently receiving steroid therapy, has recently (defined as within 2 weeks of enrollment) received such therapy, or has received 2 or more courses of high dose corticosteroids (orally or parenterally) lasting at least 1 week within 12 months prior to enrollment. Participants using inhaled, nasal, or topical corticosteroids are considered eligible for the study.
* Plans to receive during Day 1 through Month 7 of the study, is receiving or has received within the 6 months prior to the Day 1 vaccination any immune globulin product (including RhoGAM™) or blood derived product other than IVIG
* Has received a marketed HPV vaccine, or has participated in an HPV vaccine clinical study and has received either active agent or placebo
* Concurrently enrolled in clinical studies of investigational agents or studies involving collection of cervical specimens
* User of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence at the discretion of the investigator. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems as a result of alcohol use

Primary outcomes:
measure: Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Infection
timeFrame: 1 month post vaccination 3 (Month 7) up to Month 30
measure: Stage I: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 Antibodies
timeFrame: 1-month post vaccination 3 (Month 7)
measure: Stage I: Percentage of Participants Who Report at Least 1 Solicited Injection-site Adverse Event
timeFrame: up to 8 days post any vaccination
measure: Stage I: Percentage of Participants Who Report at Least 1 Solicited Systemic Adverse Event
timeFrame: up to 30 days post any vaccination
measure: Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)
timeFrame: Day 1 up to approximately Month 30
measure: Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related CIN 2/3, AIS, and cervical cancer
timeFrame: Month 7 up to Month 90
measure: Stages I/II: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)
timeFrame: Day 1 up to approximately Month 90
Secondary outcomes:
measure: Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Infection
timeFrame: 1 month post vaccination 3 (Month 7) up to Month 30
measure: Stage I: Percentage of Participants Who Seroconvert by cLIA to HPV Types 6, 11, 16, and 18
timeFrame: 1 Month Post Vaccination 3 (Month 7)
measure: Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Cervical Infection
timeFrame: 1 month post vaccination 3 (Month 7) up to Month 30
measure: Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Non-cervical Infection
timeFrame: 1 month post vaccination 3 (Month 7) up to Month 30
measure: Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Cervical Infection
timeFrame: 1 month post vaccination 3 (Month 7) up to Month 30
measure: Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Non-cervical Infection
timeFrame: 1 month post vaccination 3 (Month 7) up to Month 30
measure: Stage I: Combined Incidence of Papanicolaou (Pap) Test Abnormalities That are Related to HPV 31, 33, 45, 52, or 58
timeFrame: Month 7 up to Month 30
measure: Stage I: Geometric Mean Titers of HPV 31, 33, 45, 52 , and 58 Antibodies
timeFrame: 1 Month Post Vaccination 3 (Month 7)
measure: Stage I: Percentage of Participants Who Seroconvert by cLIA to HPV Types 31, 33, 45, 52 , and 58
timeFrame: 1 Month Post Vaccination 3 (Month 7)
measure: Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related CIN 1/2/3, AIS, and cervical cancer
timeFrame: Month 7 to Month 90
measure: Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related genital warts, CIN 2/3, AIS, cervical cancer, VIN 2/3, VaIN 2/3, vulvar cancer, and vaginal cancer
timeFrame: Month 7 up to Month 90
measure: Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related genital warts, CIN 1/2/3, AIS, cervical cancer, VIN 1/2/3, VaIN 1/2/3, vulvar cancer, and vaginal cancer
timeFrame: Month 7 to Month 90
measure: Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52- , or 58-related Cervical, Vaginal and External Genital Biopsy and Definitive Therapy
timeFrame: Month 7 up to Month 90
Other outcomes:
Locations:
city: Guilin
country: China
facility: Lingchuan Center for Disease Control and Prevention ( Site 0002)
state: Guangxi
city: Guilin
country: China
facility: Quanzhou Center for Disease Control and Prevention ( Site 0001)
state: Guangxi
city: Changzhi
country: China
facility: Xiangyuan Center for Disease Control and Prevention ( Site 0003)
state: Shanxi
city: Yuncheng
country: China
facility: Yanhu Center for Disease Control and Prevention of Yuncheng ( Site 0004)
state: Shanxi
city: Mianyang
country: China
facility: Mianyang Center for Disease Control and Prevention ( Site 0005)
state: Sichuan
city: Mianyang
country: China
facility: Santai County Center for Disease Control and Prevention ( Site 0006)
state: Sichuan
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: