GARDASIL™ Study in Healthy Females Between 9 and 26 Years of Age in Sub-Saharan Africa (V501-046)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01245764
First received: November 19, 2010
Last updated: May 1, 2014
Last verified: May 2014
  Purpose

The study is designed to determine the safety, tolerability and immunogenicity of a 3-dose regimen of GARDASIL™ administered to healthy females between 9 and 26 years of age, in Sub-Saharan Africa. Data from the current study are needed in order to complement existing extensive safety data from the GARDASIL™ clinical trials program, and confirm that GARDASIL™ may be administered safely and will induce immune responses in populations from and living in Sub-Saharan Africa, as GARDASIL™ has not previously been studied in this region of the world.


Condition Intervention Phase
Papillomavirus Infections
Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (GARDASIL™)
Biological: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Evaluation of Safety and Immunogenicity of GARDASIL™ in Healthy Females Between 9 and 26 Years of Age in SubSaharan Africa

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Who Seroconvert to Human Papillomavirus (HPV) Type 6 [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Seroconversion was defined as achieving an anti-HPV Type 6 competitive Luminex Immunoassay (cLIA) level of >=20 milli Merck U/mL. The dilution-corrected limit of detection for the Type 6 cLIA was 4.2 milli Merck U/mL.

  • Number of Participants Who Seroconvert to HPV Type 11 [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Seroconversion was defined as achieving an anti-HPV Type 11 cLIA level of >=16 milli Merck U/mL. The dilution-corrected limit of detection for the Type 11 cLIA was 3.9 milli Merck U/mL.

  • Number of Participants Who Seroconvert to HPV Type 16 [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Seroconversion was defined as achieving an anti-HPV Type 16 cLIA level of >=20 milli Merck U/mL. The dilution-corrected limit of detection for the Type 16 cLIA was 9.7 milli Merck U/mL.

  • Number of Participants Who Seroconvert to HPV Type 18 [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Seroconversion was defined as achieving an anti-HPV Type 18 cLIA level of >=24 milli Merck U/mL. The dilution-corrected limit of detection for the Type 18 cLIA was 5.8 milli Merck U/mL.

  • Number of Participants With Injection-site Adverse Experiences [ Time Frame: Up to Day 5 after any vaccination in study Phase A ] [ Designated as safety issue: Yes ]
    Participants were prompted to report injection-site experiences of pain, erythema, or swelling and were also asked to report any other injection-site adverse experiences

  • Number of Participants With Elevated Temperature (Oral Temperature >=100 °F) [ Time Frame: Up to Day 5 after any vaccination in study Phase A ] [ Designated as safety issue: Yes ]
  • Number of Participants With Serious Adverse Experiences [ Time Frame: From the time of informed consent is signed through the last study visit (up to 19 months) ] [ Designated as safety issue: Yes ]
    A serious adverse experience is any adverse experience that results in death, is life threatening, results in persistent or significant disability/incapacity, results in or prolongs existing inpatient hospitalization, is a congenital anomaly/birth defect, is a cancer, is an overdose, or is another important medical event that may jeopardize the participant and may require medical or surgical intervention


Secondary Outcome Measures:
  • Geometric Mean Titer (GMT) of Anti-HPV Type 6 Antibody [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Anti-HPV Type 6 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL.

  • GMT of Anti-HPV Type 11 Antibody [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Anti-HPV Type 11 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 16 milli Merck U/mL.

  • GMT of Anti-HPV Type 16 Antibody [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Anti-HPV Type 16 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 20 milli Merck U/mL.

  • GMT of Anti-HPV Type 18 Antibody [ Time Frame: Month 7 (1 month postdose 3 in study Phase A) ] [ Designated as safety issue: No ]
    Anti-HPV Type 18 antibodies were measured by cLIA. The seropositive cut-off threshold for this assay is defined as 24 milli Merck U/mL.


Enrollment: 250
Study Start Date: March 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GARDASIL™ 9 to 12 Years Old
GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Participants will not continue to study Phase B.
Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (GARDASIL™)
Experimental: GARDASIL™ 13 to 15 Years Old
GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Participants will not continue to study Phase B.
Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (GARDASIL™)
Experimental: GARDASIL™ 16 to 26 Years Old
GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. Participants will not continue to study Phase B.
Biological: Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine (GARDASIL™)
Placebo Comparator: Placebo 9 to 12 Years Old
Placebo to GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase A. After database lock and unblinding for study Phase A, participants will have the option to receive GARDASIL™ 0.5 mL injection at the Day 1, Month 2, and Month 6 visits in study Phase B.
Biological: Placebo

Detailed Description:

In Phase A of the study, healthy females between 9 and 12 years of age will be randomized (4:1) to receive the 3-dose regimen of GARDASIL™ or placebo, and those between 13 and 26 years old will receive GARDASIL™. In Phase B of the study, participants who received placebo in Phase A will have the option to receive the 3-dose regimen of GARDASIL™.

  Eligibility

Ages Eligible for Study:   9 Years to 26 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria :

  • Healthy subjects who are native to and living in a participating Sub-Saharan African country.
  • Subject agrees to provide study personnel with a primary telephone number as well as an alternate telephone number for follow-up purposes. If potential subject does not have a telephone number, the subject must provide an address at which he or she may be contacted.
  • Post-pubertal female subjects must not be pregnant
  • Subjects who are sexually active must agree to use effective contraception or remain abstinent through Month 7 of the study.
  • Subjects who have not yet had sexual intercourse must either agree to remain abstinent through Month 7 of the study, or if they become sexually active during the vaccination phase of the study, to use effective contraception through Month 7.
  • Subjects who have had sexual intercourse in the two weeks prior to enrollment must have been using effective contraception as defined above. (Emergency contraception is not considered effective contraception for enrollment in the study.)

Exclusion Criteria :

  • Subject is pregnant as determined by a positive pregnancy test
  • Subject has had a temperature ≥ 37.8 °C or ≥ 100 °F within 24 hours prior to the first injection.
  • Subject is currently enrolled in another clinical study of an investigational agent or agents.
  • Subject has a history of known prior vaccination with a HPV vaccine, or was previously enrolled in an HPV vaccine study and received either active agent or placebo.
  • Subject has received any inactivated vaccine within 14 days prior to enrollment or any live vaccine within 21 days prior to enrollment.
  • Subject has a history of severe allergic reaction to any agent (e.g., swelling of the mouth and throat, difficulty breathing, hypotension, or shock) that required medical intervention.
  • 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]).
  • Subject has received any immune globulin preparation or blood-derived products within the 6 months prior to the first injection, or plans to receive any such products during the course of the study.
  • Subject has a history of splenectomy, known autoimmune disorder (e.g., systemic lupus erythematosus, rheumatoid arthritis), or is receiving immunosuppressives (e.g., substances or treatments known to diminish immune response such as radiation therapy, administration of antimetabolites, antilymphocytic sera, systemic corticosteroids). Individuals who have received periodic treatments with immunosuppressives, defined as at least 3 courses of systemic corticosteroids each lasting at least 1 week in duration for the year prior to enrollment, will be excluded. Subjects using topical steroids (i.e., inhaled or nasal) will be eligible for vaccination.
  • Subject is immunocompromised or has been diagnosed as having Human Immunodeficiency Virus (HIV) infection
  • Subject has known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections.
  • Subject has known sickle cell anemia disease, active malaria or active tuberculosis.
  • Subject has any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives.
  • Subject has a history of recent or ongoing alcohol or other drug abuse.
  • Female subject has a prior history of abnormal Pap test showing squamous intraepithelial lesion (SIL), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells, cannot rule out a high grade lesion (ASC-H), or biopsy showing cervical intraepithelial neoplasia (CIN) or worse.
  • Subject has any prior history (or at Day 1) of genital warts or treatment for genital warts.
  • Subject with >4 lifetime sexual partners.
  • Subject has undergone hysterectomy with removal of the cervix.
  • Subject plans to permanently relocate from the area prior to the completion of the study or to leave for an extended period of time when study visits would need to be scheduled.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01245764     History of Changes
Other Study ID Numbers: V501-046
Study First Received: November 19, 2010
Results First Received: February 4, 2014
Last Updated: May 1, 2014
Health Authority: Kenya: Pharmacy and Poisons Board

Keywords provided by Merck Sharp & Dohme Corp.:
Cervical cancer
vulvar cancer
vaginal cancer
genital warts
human papillomavirus

Additional relevant MeSH terms:
Papillomavirus Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections

ClinicalTrials.gov processed this record on October 16, 2014