Prevention of cervical,vulvar,vaginal, and anal cancers and related precancers, external genital lesions, Pap test abnormalities, and persistent infection caused by HPV Types 6,11,16,18,31,33,45,52,58 MedDRA version: 20.0 Level: PT Classification code 10061331 Term: Papilloma viral infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: GARDASIL®9
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Human Papillomavirus Type 6 L1 protein
Other descriptive name:
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck Co., Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be included in the study and to receive the first study vaccination, subjects must meet all inclusion criteria. For items with an asterisk (*), if the subject does not meet these inclusion criteria, the Day 1 visit may be rescheduled for a time when these criteria can be met. 1. Independent Ethics Committee (IEC)-approved written informed consent form (ICF) and privacy language as per national regulations must be obtained from the subject and/or from the subject’s parent(s) or legal guardian(s) prior to any study-related procedures (including discontinuation of prohibited medication, if applicable); assent (for minor subjects) by the subject is given as required by local law. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 2. Subject is a woman between the ages 16 years and 0 days and 45 years and 364 days as of first vaccination. 3. Subject is judged to be in good physical health on the basis of medical history, physical examination (if deemed necessary), and laboratory testing. 4. Subject, or subject's parent or guardian, is able to understand and adhere to the study procedures (e.g., is not planning to relocate far from the investigational centre during the study period); is able to read, understand, and complete the electronic vaccination report card (eVRC); is able to understand the risks involved with the study; and voluntarily agrees to participate in the study by giving written informed consent. 5. *Since the first day of the subject’s last menstrual period through Day 1, the subject has not had sex with males or has had sex with males and used effective contraception with no failures (an example of a failure is a male condom that ruptures during sexual intercourse). Effective contraception is defined as a marketed, approved contraceptive product that the subject has used per the manufacturer’s instructions with every act of sexual intercourse. The subject understands and agrees that during the Day 1 through Month 7 period, she should not have sexual intercourse with males without effective contraception, and the uses of the rhythm method alone, withdrawal alone, and emergency contraception, are not acceptable methods per the protocol. Subjects who have reached menopause, undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation are eligible without the use of contraceptives. Postmenopausal status is defined as: (1) No menses for >1 year but =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: To be included and receive the first study vaccination, subjects should not have any exclusion criteria. For items with an asterisk (*), if the subject meets these exclusion criteria, the Day 1 visit may be rescheduled for a time when these criteria are not met. 1. Subject has a history of an abnormal Pap test or abnormal cervical biopsy results (showing cervical intraepithelial neoplasia or worse) or cervical disease (i.e., surgical treatment for cervical lesions). 2. Subject has history of genital warts, Vulvar Intraepithelial Neoplasia or Vaginal Intraepithelial Neoplasia. 3. Subject has a history of a positive test for HPV. 4. Subject has a history of known prior vaccination with an HPV vaccine, i.e., received a marketed HPV vaccine, or has participated in an HPV vaccine clinical study and has received either active agent or placebo. 5. Subject is pregnant (as determined by serum or urine pregnancy test). 6. Subject is, at the time of signing ICF, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence. Alcohol abusers are defined as those who drink despite recurrent social, interpersonal, and/or legal problems as a result of alcohol use. 7. Subject has a history of severe allergic reaction, including known allergy to any vaccine component, including aluminum, yeast, or BENZONASE® (nuclease, Nycomed [used to remove residual nucleic acids from this and other vaccines]) (e.g., swelling of the mouth and throat, difficulty breathing, hypotension or shock) that met the criteria for serious adverse experiences defined in this protocol. 8. Subject has had a splenectomy, or is currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukaemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune or immunosuppressive condition, or has a history of any disease, which, in the investigator’s opinion, may confound the results of the study or pose an additional risk to the subject. 9. Subject is receiving or has received in the year prior to enrolment the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (tumour necrosis factor-a antagonists, monoclonal antibody therapies (including rituximab [Rituxan]), intravenous gamma globulin, antilymphocyte sera, or other therapy known to interfere with the immune response. With regard to systemic corticosteroids, a subject will be excluded if she is currently receiving steroid therapy, has recently (defined as within 2 weeks of enrolment) received such therapy, or has received 2 or more courses of high dose corticosteroids (=20mg/day of prednisone [or equivalent] orally or parenterally) lasting at least 1 week in duration in the year prior to enrolment. Subjects using inhaled, nasal, or topical corticosteroids are considered eligible for the study. 10. Subject has received any immune globulin or blood-derived product within the 3 months prior to the Day 1 vaccination, or plans to receive any such product during Day 1 through Month 7 of the study. 11. * Subject has received non-replicating (i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that the administration of GARDASIL®9 in 27- to 45 year old women induces non inferior geometric mean titres (GMTs) for serum anti-HPV 16, 18, 31, 33, 45, 52, and 58 compared with 16- to 26-year-old women.; Secondary Objective: To evaluate the safety/tolerability of GARDASIL®9 in 27- to 45-year-old women compared with 16 to 26-year-old women. To demonstrate that GARDASIL®9 is immunogenic with respect to HPV types 16, 18, 31, 33, 45, 52, and 58 in 27- to 45-year-old women. To summarize humoral immune responses (including anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 GMTs and seroconversion rates at Day 1 and 4 weeks after Dose 3) in 16- to 26-year-old and 27- to 45-year-old women who received GARDASIL®9. ;Primary end point(s): The primary immunogenicity endpoints are the cLIA GMTs to HPV 16, 18, 31, 33, 45, 52 and 58.;Timepoint(s) of evaluation of this end point: at 4 weeks after Dose 3. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary immunogenicity endpoints are: the cLIA seroconversion percentages to HPV 16, 18, 31, 33, 45, 52 and 58 in 27- to 45-year-old women. the cLIA GMTs and the cLIA seroconversion percentages to each of HPV 6,11,16,18,31,33,45,52, and 58 in 16- to 26-year-old women and 27- to 45 year-old women. The Safety assessment will focus on injection site adverse reactions and elevated temperatures reported on the electronic VRC. SAEs, pregnancy, and pregnancy-related events will be collected. ; Timepoint(s) of evaluation of this end point: Immunogenicity: by 4 weeks after Dose 3. Safety: for injection Day 1 to Day 5 post-vaccination and systemic AEs Day 1 to Day 15 post-vaccination. For SAEs, pregnancy, and pregnancy-related events , from the time the ICF is signed through 1 month following the last vaccination | — |
Countries
Austria, Belgium, Finland, Germany, Italy, Spain
Contacts
Public ContactFrederick Wittke
Merck Sharp & Dohme Corp., a subsidiary of Merck Co., Inc.
Outcome results
None listed