Clinical trial NCT00090220: A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501, qHPV) in Mid-Adult Women (V501-019)
Official title: Safety, Immunogenicity, and Efficacy of Gardasil (V501 (Human Papilloma Virus [Types 6, 11, 16, 18] Recombinant Vaccine) in Mid-Adult Women - The FUTURE III (Females United to Unilaterally Reduce Endo/Ectocervical Cancer) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy Adult Female Participants
Prevention
Papillomavirus Infection
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2004-08-27
Enrollment: 3819
Sex: FEMALE
Minimum age (years): 24
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study was conducted to assess the safety, immunogenicity, efficacy and long-term effectiveness of a vaccine being evaluated for the prevention of human papillomavirus (HPV) infection and disease in mid-adult women.

Detailed description: The Base study vaccination period (V501-019) encompassed Day 1 through Month 7, during which time participants received randomly assigned, blinded Gardasil™ (V501, qHPV vaccine) or placebo at Day 1, Month 2 and Month 6. The Base study follow-up period continued through approximately Month 48.

The base study was extended in protocol V501-019-10 (EXT1). Participants who received placebo and participants who received only 1 dose of qHPV vaccine in the Base Study were offered a complete, open-label, 3-dose qHPV vaccine regimen (administered at EXT1 Day 1, Month 2 and Month 6). Participants who received only 2 doses of qHPV vaccine in the base study were offered a single additional dose of qHPV vaccine (administered at EXT1 Day 1). Participants were followed to EXT1 Month 7.

A Long Term Follow-Up (LTFU) extension study V501-019-21 (EXT2) was added to observe the long term safety, effectiveness, and immunogenicity of qHPV vaccine in approximately 1,600 women who participated in the Base Study at sites in Colombia. Data were collected over a period of 6-10 years following participant's enrollment in the original Base Study.

Eligibility criteria: Inclusion Criteria:

* No history of genital warts, vulvar intraepithelial neoplasia (VIN), or vaginal intraepithelial neoplasia (VaIN)
* Not pregnant and agrees to use effective contraception through Month 7 of the study
* Additional criteria applied

Exclusion Criteria:

* Pregnant
* Concurrently enrolled in a clinical study involving collection of cervical specimens
* Previously received any HPV vaccine
* History of severe allergic reaction that required medical intervention
* Received any immune globulin or blood-derived products within 3 months prior to the first study injection
* History of splenectomy, known immune disorders, or receiving immunosuppressives
* Immunocompromised or diagnosed with human immunodeficiency virus (HIV) infection
* Known thrombocytopenia or any coagulation disorders that could contraindicate intramuscular injections
* History of recent or ongoing alcohol or drug abuse
* Prior treatment for genital warts, VIN, or VaIN
* History of cervical disease (ie, surgical treatment for cervical lesions)
* Hysterectomy

Primary outcomes:
measure: Incidence Rate of HPV 6/11/16/18 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer
timeFrame: Up to 48 months (4 years) after the first dose of qHPV vaccine in the Base Study
measure: Number of Participants With Vaccine- or Placebo-Related Serious Adverse Events (SAEs) in the Base Study
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
measure: Number of Participants With Vaccine-Related SAEs After Vaccine Administration
timeFrame: qHPV in Base Study: Up to Month 120; Placebo in Base Study: approximately Month 60 up to Month 120
measure: Number of Participants With an SAE Resulting in Death After Vaccine Administration
timeFrame: qHPV in Base Study: Up to Month 120; Placebo in Base Study: approximately Month 60 up to Month 120
measure: Cumulative Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN) or Condyloma: Day 1 to Year 4
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
measure: Cumulative Incidence of HPV 6/11/16/18-related CIN or Condyloma: Year 4 to 8
timeFrame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study
measure: Cumulative Incidence of HPV 6/11/16/18-related CIN or Condyloma: Year 6 to 10
timeFrame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study
measure: Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Day 1 to Year 4
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
measure: Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Year 4 to 8
timeFrame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study
measure: Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Year 6 to 10
timeFrame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 1 Month Postdose 3 in the Base Study
timeFrame: Month 7 (1 month after the third dose of qHPV vaccine in the Base Study)
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 6 Months Postdose 3 in the Base Study
timeFrame: Month 12 (6 months after the third dose of qHPV vaccine in the Base Study)
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 18 Months Postdose 3 in the Base Study
timeFrame: Month 24 (18 months after the third dose of qHPV vaccine in the Base Study)
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 30 Months Postdose 3 in the Base Study
timeFrame: Month 36 (30 months after the third dose of qHPV vaccine in the Base Study)
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 42 Months Postdose 3 in the Base Study
timeFrame: Month 48 (42 months after the third dose of qHPV vaccine in the Base Study)
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 66 Months Postdose 3 in the Base Study
timeFrame: Month 72 (66 months after the third dose of qHPV vaccine in the Base Study)
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 90 Months Postdose 3 in the Base Study
timeFrame: Month 96 (90 months after the third dose of qHPV vaccine in the Base Study)
measure: Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 114 Months Postdose 3 in the Base Study
timeFrame: Month 120 (114 months after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 1 Month Postdose 3 in the Base Study
timeFrame: Month 7 (1 month after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 6 Months Postdose 3 in the Base Study
timeFrame: Month 12 (6 months after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 18 Months Postdose 3 in the Base Study
timeFrame: Month 24 (18 months after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 30 Months Postdose 3 in the Base Study
timeFrame: Month 36 (30 months after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 42 Months Postdose 3 in the Base Study
timeFrame: Month 48 (42 months after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 66 Months Postdose 3 in the Base Study
timeFrame: Month 72 (66 months after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 90 Months Postdose 3 in the Base Study
timeFrame: Month 96 (96 months after the third dose of qHPV vaccine in the Base Study)
measure: Percentage of Participants Seropositive for Anti-HPV Antibody at 114 Months Postdose 3 in the Base Study
timeFrame: Month 120 (114 months after the third dose of qHPV vaccine in the Base Study)
Secondary outcomes:
measure: Incidence Rate of HPV 6/11 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
measure: Cumulative Incidence of HPV 6/11-related Condyloma: Day 1 to Year 4
timeFrame: Up to 48 months (4 years) after the first dose of qHPV vaccine or placebo in the Base Study
measure: Cumulative Incidence of HPV 6/11-related Condyloma: Year 4 to Year 8
timeFrame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study
measure: Cumulative Incidence of HPV 6/11-related Condyloma: Year 6 to Year 10
timeFrame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study
measure: Incidence Rate of HPV 6/11-related Condyloma (Secondary Analysis): Day 1 to Year 4
timeFrame: Up to 48 months (4 years) after the first dose of qHPV vaccine or placebo in the Base Study
measure: Incidence Rate of HPV 6/11-related Condyloma (Secondary Analysis): Year 4 to Year 8
timeFrame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study
measure: Incidence Rate of HPV 6/11-related Condyloma (Secondary Analysis): Year 6 to Year 10
timeFrame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study
measure: Incidence Rate of HPV 31/33/35/52/58 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
Other outcomes:
measure: Incidence Rate of HPV 16/18 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
measure: Cumulative Incidence of HPV 16/18-related CIN 2 or Worse: Day 1 to Year 4
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
measure: Cumulative Incidence of HPV 16/18-related CIN 2 or Worse: Year 4 to 8
timeFrame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study
measure: Cumulative Incidence of HPV 16/18-related CIN 2 or Worse: Year 6 to 10
timeFrame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study
measure: Incidence Rate of HPV 16/18-related CIN 2 or Worse (Secondary Analysis): Day 1 to Year 4
timeFrame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)
measure: Incidence Rate of HPV 16/18-related CIN 2 or Worse (Secondary Analysis): Year 4 to 8
timeFrame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study
measure: Incidence Rate of HPV 16/18-related CIN 2 or Worse (Secondary Analysis): Year 6 to 10
timeFrame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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