Skip to main content
OpenTrials
Completed

NCT Number: NCT00090220

A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501, qHPV) in Mid-Adult Women (V501-019)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Healthy Adult Female Participants Communicable Diseases DNA Virus Infections Disease Attributes Genital Diseases Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 Infections Papillomavirus Infection Papillomavirus Infections Pathologic Processes Pathological Conditions, Signs and Symptoms Prevention Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Tumor Virus Infections Urogenital Diseases Virus Diseases

Age range

24 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

Biological

qHPV intramuscular injection in three 0.5 mL doses over 6 months in the Base Study or EXT1

Comparator: Placebo

Biological

Placebo intramuscular injection in three 0.5 mL doses over 6 months.

Primary outcomes

  1. 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

    Time frame: Up to 48 months (4 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by polymerase chain reaction (PCR) testing. VIN = vulvar intraepithelial neoplasia; VaIN = vaginal intraepithelial neoplasia; AIS = adenocarcinoma in situ.

  2. Number of Participants With Vaccine- or Placebo-Related Serious Adverse Events (SAEs) in the Base Study

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or is an overdose. Vaccine-related SAEs are those deemed by the investigator to be definitely, probably, or possibly related to study vaccine.

  3. Number of Participants With Vaccine-Related SAEs After Vaccine Administration

    Time frame: qHPV in Base Study: Up to Month 120; Placebo in Base Study: approximately Month 60 up to Month 120

    An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or is an overdose. Vaccine-related SAEs are those deemed by the investigator to be definitely, probably, or possibly related to study vaccine.

  4. Number of Participants With an SAE Resulting in Death After Vaccine Administration

    Time frame: qHPV in Base Study: Up to Month 120; Placebo in Base Study: approximately Month 60 up to Month 120

    An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event. A serious adverse event (SAE) is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, or is an overdose.

  5. Cumulative Incidence of HPV 6/11/16/18-related Cervical Intraepithelial Neoplasia (CIN) or Condyloma: Day 1 to Year 4

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Day 1 to Year 4, conditional on having been event-free at Day 1.

  6. Cumulative Incidence of HPV 6/11/16/18-related CIN or Condyloma: Year 4 to 8

    Time frame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 4 to Year 8, conditional on having been event-free from Day 1 to Year 4. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

  7. Cumulative Incidence of HPV 6/11/16/18-related CIN or Condyloma: Year 6 to 10

    Time frame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 6 to Year 10, conditional on having been event-free from Day 1 to Year 6.

  8. Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Day 1 to Year 4

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    The four HPV types were determined by PCR testing.

  9. Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Year 4 to 8

    Time frame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

  10. Incidence Rate of HPV 6/11/16/18-related CIN or Condyloma (Secondary Analysis): Year 6 to 10

    Time frame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing.

  11. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 1 Month Postdose 3 in the Base Study

    Time frame: Month 7 (1 month after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  12. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 6 Months Postdose 3 in the Base Study

    Time frame: Month 12 (6 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  13. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 18 Months Postdose 3 in the Base Study

    Time frame: Month 24 (18 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  14. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 30 Months Postdose 3 in the Base Study

    Time frame: Month 36 (30 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  15. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 42 Months Postdose 3 in the Base Study

    Time frame: Month 48 (42 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  16. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 66 Months Postdose 3 in the Base Study

    Time frame: Month 72 (66 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  17. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 90 Months Postdose 3 in the Base Study

    Time frame: Month 96 (90 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  18. Geometric Mean Titer for Anti-HPV Type 6, 11, 16, and 18 Antibody at 114 Months Postdose 3 in the Base Study

    Time frame: Month 120 (114 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to the HPV Types were determined by Competitive Luminex Immunoassay (cLIA). Geometric Mean Titers (GMT) are reported in milli-Merck Units/mL (mMU/mL). This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  19. Percentage of Participants Seropositive for Anti-HPV Antibody at 1 Month Postdose 3 in the Base Study

    Time frame: Month 7 (1 month after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  20. Percentage of Participants Seropositive for Anti-HPV Antibody at 6 Months Postdose 3 in the Base Study

    Time frame: Month 12 (6 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  21. Percentage of Participants Seropositive for Anti-HPV Antibody at 18 Months Postdose 3 in the Base Study

    Time frame: Month 24 (18 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  22. Percentage of Participants Seropositive for Anti-HPV Antibody at 30 Months Postdose 3 in the Base Study

    Time frame: Month 36 (30 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  23. Percentage of Participants Seropositive for Anti-HPV Antibody at 42 Months Postdose 3 in the Base Study

    Time frame: Month 48 (42 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  24. Percentage of Participants Seropositive for Anti-HPV Antibody at 66 Months Postdose 3 in the Base Study

    Time frame: Month 72 (66 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  25. Percentage of Participants Seropositive for Anti-HPV Antibody at 90 Months Postdose 3 in the Base Study

    Time frame: Month 96 (96 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

  26. Percentage of Participants Seropositive for Anti-HPV Antibody at 114 Months Postdose 3 in the Base Study

    Time frame: Month 120 (114 months after the third dose of qHPV vaccine in the Base Study)

    Serum antibodies to HPV Types 6, 11, 16, and 18 were determined by Competitive Luminex Immunoassay (cLIA). The seropositive thresholds (in mMU/mL) were >20 for Type 6, >16 for Type 11, >20 for Type 16, and >24 for Type 18. This Outcome Measure evaluated age-specific immunogenicity responses, and applied only to participants who received qHPV in the Base Study.

Secondary outcomes

  1. Incidence Rate of HPV 6/11 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    HPV 6/11: The two types of HPV (types 6/11) were determined by PCR testing

  2. Cumulative Incidence of HPV 6/11-related Condyloma: Day 1 to Year 4

    Time frame: Up to 48 months (4 years) after the first dose of qHPV vaccine or placebo in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Day 1 to Year 4 conditional on having been event-free at Day 1.

  3. Cumulative Incidence of HPV 6/11-related Condyloma: Year 4 to Year 8

    Time frame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 4 to Year 8 conditional on having been event-free from Day 1 to Year 4. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

  4. Cumulative Incidence of HPV 6/11-related Condyloma: Year 6 to Year 10

    Time frame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 6 to Year 10 conditional on having been event-free from Day 1 to Year 6.

  5. Incidence Rate of HPV 6/11-related Condyloma (Secondary Analysis): Day 1 to Year 4

    Time frame: Up to 48 months (4 years) after the first dose of qHPV vaccine or placebo in the Base Study

    The four HPV types were determined by PCR testing.

  6. Incidence Rate of HPV 6/11-related Condyloma (Secondary Analysis): Year 4 to Year 8

    Time frame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

  7. Incidence Rate of HPV 6/11-related Condyloma (Secondary Analysis): Year 6 to Year 10

    Time frame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 6 to Year 10 conditional on having been event-free from Day 1 to Year 6.

  8. 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

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    This outcome measure was not analyzed because of diminished interest by experts in composite efficacy endpoints associated with these HPV types

Other outcomes

  1. Incidence Rate of HPV 16/18 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    HPV 16/18: The two types of HPV (types 16/18) were determined by PCR testing

  2. Cumulative Incidence of HPV 16/18-related CIN 2 or Worse: Day 1 to Year 4

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Day 1 to Year 4 conditional on having been event-free at Day 1.

  3. Cumulative Incidence of HPV 16/18-related CIN 2 or Worse: Year 4 to 8

    Time frame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 4 to Year 8 conditional on having been event-free from Day 1 to Year 4. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

  4. Cumulative Incidence of HPV 16/18-related CIN 2 or Worse: Year 6 to 10

    Time frame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. Cumulative incidence probability is the probability of becoming an endpoint case at any time from Year 6 to Year 10 conditional on having been event-free from Day 1 to Year 6.

  5. Incidence Rate of HPV 16/18-related CIN 2 or Worse (Secondary Analysis): Day 1 to Year 4

    Time frame: Up to Month 48 (up to 42 months after the third dose of qHPV vaccine in the Base Study)

    The four HPV types were determined by PCR testing.

  6. Incidence Rate of HPV 16/18-related CIN 2 or Worse (Secondary Analysis): Year 4 to 8

    Time frame: From 48 to 96 months (4 to 8 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing. The analysis windows were cut at the exact time points, e.g., Year 4. Visits and events which occurred after Year 4 due to visit window or follow-up investigations are included in the Year 4 to Year 8 time interval.

  7. Incidence Rate of HPV 16/18-related CIN 2 or Worse (Secondary Analysis): Year 6 to 10

    Time frame: From 72 to 120 months (6 to 10 years) after the first dose of qHPV vaccine in the Base Study

    The four HPV types were determined by PCR testing.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2004
Primary completion
2009
Study completion
2015
First posted
Aug 27, 2004
Registry last updated
Apr 21, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.