Prevention of cervical, vulvar, and vaginal cancers and related precancers, external genital lesions, and persistent infection caused by Human Papillomavirus (HPV) 6, 11, 16, 18, 31, 45, 52, and 58. MedDRA version: 8.1 Level: LLT Classification code 10063001 Term: Human papilloma virus infection
Conditions
Interventions
Product Name: Octavalent HPV VLP Vaccine
Product Code: V502
Pharmaceutical Form: Suspension for injection
Trade Name: GARDASIL
Product Name: GARDASIL™[Quadrivalent Human Papillomavirus (Types 6, 11,
Sponsors
Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be randomized and receive the first study vaccination, subjects should 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. Subject is female, between the ages of 16 years and 0 days and 26 years and 364 days on the day of randomization. 2. Subject (or, for minor subjects, parent/legal guardian and subject) fully understands study procedures, alternative treatments available, the risks involved with the study, and voluntarily agrees to participate by giving written informed consent. 3. Subject is able to read, understand, and complete the vaccination report card. 4. Subject is judged to be in good physical health on the basis of medical history, physical examination, and laboratory results. 5. The subject has the following lifetime sexual history at the time of enrollment: a) Subject has had 1 to 4 male and/or female sexual partners; or b) Subject has had 0 male and/or female sexual partners, is 18 years of age or older, and plans to become sexually active within the first 3 months of the study. Male partner is defined as someone with whom the subject has penile penetrative sexual intercourse. Female partner is defined as someone who has contacted, either by penetrative (with fingers or other objects) or non-penetrative means, the subject’s genitalia during sexual activity. 6. *Subject has refrained from douching/vaginal cleansing and using vaginal medications or preparations for 2 calendar days prior to the Day 1 visit. Subject agrees to refrain from these activities for 2 calendar days prior to any future visit that includes collection of study specimens (cervical/genital swabs, Pap test, or biopsy/definitive therapy tissue). 7. *Subject has refrained from sexual activity (including anal, vaginal, or genital/genital contact whether same sex or opposite sex) for 2 calendar days prior to the Day 1 visit. Subject agrees to refrain from these sexual activities for 2 calendar days prior to any future visit that includes collection of study specimens (cervical/genital swabs, Pap test, or biopsy/definitive therapy tissue). 8. *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. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: To be randomized 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 (showing ASC-US or worse) or an abnormal cervical biopsy result (showing cervical intraepithelial neoplasia [CIN] or worse). 2. Subject has never had a history of an abnormal Pap test, but has a history of a positive test for HPV. 3. Subject is, at the time of signing informed consent, 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. 4. Subject has a history of severe allergic reaction (e.g., swelling of the mouth and throat, difficulty breathing, hypotension or shock) that required medical intervention. 5. Subject has known allergy to any vaccine component, including aluminum, yeast, or BENZONASE™ (nuclease, Nycomed™ [used to remove residual nucleic acids from this and other vaccines]). For the purpose of this exclusion criterion, an allergy to vaccine components is defined as an allergic reaction that met the criteria for serious adverse experiences defined in Section 3.4. 6. Subject is currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), inflammatory bowel disease, or other autoimmune condition. 7. Subject has had a splenectomy. 8. Subject is receiving or has received in the year prior to enrollment the following immunosuppressive therapies: radiation therapy, cyclophosphamide, azathioprine, methotrexate, any chemotherapy, cyclosporin, leflunomide (Arava™), TNF-a 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 subject 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 in duration in the year prior to enrollment. Subjects using inhaled, nasal, or topical corticosteroids are considered eligible for the study. 9. Subject has received any immune globulin product (including RhoGAM™ [Ortho- Clinical Diagnostics]) 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. 10. *Subject has received non-replicating (inactivated) vaccines within 14 days prior to the Day 1 vaccination or has received replicating (live virus) vaccines within 21 days prior to the Day 1 vaccination. 11. Subject has thrombocytopenia or other coagulation disorder that would contraindicate intramuscular injections. 12. *Subject has donated blood within 1 week prior to the Day 1 vaccination, or intends to donate during Day 1 through Month 7 of the study. 13. Subject is expecting to donate eggs during Day 1 through Month 7 of the study. 14. Subject is concurrently enrolled in clinical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the tolerability of the octavalent HPV L1 VLP vaccine when administered to 16- to 26-year-old women. To demonstrate that administration of octavalent HPV L1 VLP vaccine will reduce the combined incidence of HPV 31-, 45-, 52-, and 58-related cervical, vulvar, and vaginal cancer, AIS, CIN 2/3, VIN 2/3, VaIN 2/3, CIN 1, VIN 1, VaIN 1, genital warts, and persistent infection, compared with GARDASIL™ in 16- to 26-year-old adolescent and young adult women who are seronegative at Day 1 and PCR negative Day 1 through Month 7 to the relevant HPV type. To confirm that the octavalent HPV L1 VLP vaccine induces noninferior immune responses for anti-HPV 6, 11, 16, and 18 compared to GARDASIL™;Secondary Objective: To confirm the octavalent HPV L1 VLP vaccine formulation for use in Phase III trials with respect to HPV types 31, 45, 52, and 58. To evaluate the persistence of anti-HPV 6, 11, 16, 18, 31, 45, 52, and 58 responses generated by octavalent HPV L1 VLP vaccine. To evaluate whether the administration of octavalent HPV L1 VLP vaccine results in a combined incidence of persistent HPV 6, 11, 16, and 18 infection and HPV 6-, 11-, 16-, and 18-related cervical, vulvar, and vaginal disease that is comparable to the combined incidence observed with GARDASIL™.;Primary end point(s): The primary efficacy case of persistent HPV 31, 45, 52, or 58 infection or HPV 31-, 45-, 52-, or 58-related cervical, vulvar, or vaginal cancer, AIS, CIN 2/3, VIN 2/3, VaIN 2/3, CIN 1, VIN 1, VaIN 1, or condyloma acuminata is defined as a subject, who, after the completion of the Month 7 visit, is found to have an incident case of persistent HPV 31, 45, 52 or 58 infection, or HPV 31/45/52/58-related clinical disease defined as any of the following: genital warts (condyloma acuminata), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), cervical dysplasia (any grade cervical intraepithelial neoplasia [CIN]), Adenocarcinoma in Situ (AIS), and cer | — |
Countries
Denmark
Outcome results
None listed