Cervical Intraepithelial Neoplasm (CIN) in Women (Gardasil) (V501-015)
- Conditions
- Cervical CancerGenital Warts
- Interventions
- Biological: Gardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccineBiological: Matching Placebo
- Registration Number
- NCT00092534
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The primary purpose of the study is to determine if GARDASIL™ (V501) is able to prevent cervical cancer.
- Detailed Description
In the 4-year Base Study (V501-015) (NCT00092534), participants were randomized in a 1:1 order to receive 3 doses of GARDASIL™ or matching placebo at Day 1, Month 2, and Month 6 and were assessed for efficacy, immunogenicity, and safety.
In the Base Study Extension (EXT) \[V501-015-10\], participants who received placebo or only 1 dose of GARDASIL™ in the Base Study, were given 3 doses of open-label GARDASIL™ at EXT Day 1, EXT Month 2, and EXT Month 6, and were followed to EXT Month 7. Participants who who received 2 doses of GARDASIL™ in the Base Study were given 1 dose of GARDASIL™ at EXT Day 1 and were followed for 15 days (day of vaccination plus 14 days).
In the 10-year Base Study Long-Term Follow-Up (LTFU) \[V501-015-21\] the effectiveness, immunogenicity and safety of GARDASIL™ was assessed during a period of 10 years following completion of the Base Study (V501-015) \[14 years after the first dose of GARDASIL™\] and, for some measures, the Base Study EXT (V501-015-10) \[10 years after the first dose of GARDASIL™\]. Participants from Denmark, Iceland, Norway and Sweden who participated in the Base Study were eligible to enroll in the LTFU. Effectiveness and safety was assessed by registry-based follow-up, and immunogenicity was assessed by serological testing at approximately Year 5 and Year 10 of the V501-015-21 LTFU.
An 8-year extension was added to the LTFU (V501-015-22\] to continue the evaluation of the long-term effectiveness and immunogenicity of GARDASIL™. Effectiveness and safety will be assessed by registry-based follow-up, and immunogenicity will be assessed by serological testing at approximately Year 4 and Year 8 of the extension of the LTFU.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 12167
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Quadrivalent Human Papillomavirus (HPV) Vaccine Gardasil, human papillomavirus (type 6, 11, 16, 18) recombinant vaccine The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 1 were vaccinated (at Day 1, Month 2 and Month 6) with the Quadrivalent HPV vaccine. Placebo Matching Placebo The Vaccination Period for the base study encompassed Day 1 through Month 7, during which time study subjects in Group 2 were vaccinated (at Day 1, Month 2 and Month 6) with placebo.
- Primary Outcome Measures
Name Time Method Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Base Study Up to 4 years This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine consensus diagnosis of CIN 2 or worse up to 4 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, adenocarcinoma in situ (AIS) or cervical cancer related to HPV 16 or 18.
Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 16/18-related Cervical Intraepithelial Neoplasia (CIN) 2 or Worse in the Long-term Follow-up (LTFU) Study Up to 14 years since Vaccine Dose 1 This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Incidence of the Composite Endpoint of HPV16/18-related CIN 2 or Worse in the Long-term Follow-up (LTFU) Study up to 22 years post Vaccination Dose 1 This measure is defined to have occurred when, on a single cervical biopsy, ECC, LEEP, or conization specimen, there was HPV Vaccine NPP consensus diagnosis of CIN 2 or worse up to 22 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to HPV 16 or 18. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU will be included.
- Secondary Outcome Measures
Name Time Method Number of Participants With Anti-Human Papillomavirus (HPV) 6 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study Month 7 (4 weeks after Vaccination 3) Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 6 pseudovirions in vitro; thus, the number of participants with anti-HPV 6 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study At 168 months since Vaccination Dose 1 Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 168 were 9, 6, 5, and 5 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study At 216 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 216 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) ) in the Long-Term Follow-Up (LTFU) Study At 216 months since Vaccination Dose 1 Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized.
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study At 264 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types will be measured using IgG LIA..
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 264 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study At 264 months since Vaccination Dose 1 Antibodies to HPV types will be measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 are 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. The percentage of participants that are seropositive for each type will be summarized.
Number of Participants With Anti-Human Papillomavirus (HPV) 11 Titer ≥16 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study Week 4 Postdose 3 Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 11 virions in vitro; thus, the number of participants with anti-HPV 11 ≥16 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Number of Participants With Anti-Human Papillomavirus (HPV) 16 Titer ≥20 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study Week 4 Postdose 3 Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 16 pseudovirions in vitro; thus, the number of participants with anti-HPV 16 ≥20 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Number of Participants With Anti-Human Papillomavirus (HPV) 18 Titer ≥24 mMU/mL Based on Competitive Luminex Immunoassay (cLIA) in the Base Study Week 4 Postdose 3 Anti-HPV levels \>20 mMU/mL neutralize a large input load of HPV 18 pseudovirions in vitro; thus, the number of participants with anti-HPV 18 ≥24 mMU/mL 4 four weeks after the third quadrivalent HPV (qHPV) or placebo vaccination in the Base Study was determined.
Incidence of the Composite Endpoint of Human Papillomavirus (HPV) 31/33/35/39/45/51/52/56/58/59-related Cervical Intraepithelial Neoplasia (CIN) Grade 2 or Worse in the Long-term Follow-up (LTFU) Study Up to 14 years since Vaccination Dose 1 This measure is defined to have occurred when, on a single cervical biopsy, endocervical curettage (ECC), loop electrosurgical excision procedure (LEEP), or conization specimen, there was HPV Vaccine Nordic pathology panel (NPP) consensus diagnosis of CIN 2 or worse related to nonvaccine HPV types up to 14 years after the first vaccination. For this measure, CIN 2 or worse includes CIN 2, CIN 3, AIS or cervical cancer related to nonvaccine HPV types 31, 33, 35, 39, 45, 51, 52, 56, 58, or 59. Only participants who received qHPV vaccine during the Base Study vaccination period and consented for inclusion in the LTFU are included. Because the objective was to demonstrate qHPV vaccine prophylactic efficacy at 14 years, Cohort 2 was not included in the analysis.
Incidence of the Composite Endpoint of HPV 6/11/16/18-related CIN (Any Grade), AIS, Cervical Cancer, Vulvar Cancer or Vaginal Cancer the Long-term Follow-up (LTFU) Study up to 22 years since Vaccination Dose 1 This measure is defined to have occurred if on a single biopsy or excised tissue, there is the NPP consensus diagnosis of CIN 1, CIN 2, CIN 3, AIS, cervical cancer, vulvar cancer or vaginal cancer AND at least 1 of HPV types 6, 11, 16 or 18 is detected by Thin-section PCR in an adjacent section from the same tissue block.
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study At 108 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study At 168 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types were measured using cLIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study At 108 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by competitive Luminex Immunoassay (cLIA); the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Competitive Luminex Immunoassay (cLIA) in the Long-Term Follow-Up (LTFU) Study At 168 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types were measured using cLIA. Seropositivity was assessed by cLIA; the serostatus cut-offs for anti-HPV 6, 11, 16 and 18 serum cLIA were 20, 16, 20 and 24 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study At 108 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Geometric Mean Titers (GMTs) to HPV Types 6, 11, 16, and 18 at Month 168 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study At 168 months since Vaccination Dose 1 Antibodies to human papillomavirus (HPV) types were measured using IgG LIA. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.
Percentage of Participants With Seropositivity to HPV Types 6, 11, 16, and 18 at Month 108 Assessed by Immunoglobulin G Luminex Immunoassay (IgG LIA) in the Long-Term Follow-Up (LTFU) Study At 108 months since Vaccination Dose 1 Antibodies to HPV types were measured using anti-HPV IgG LIA. The serostatus cut-offs for IgG LIA anti-HPV 6, 11, 16 and 18 at Month 108 were 15, 15, 7, and 10 milliMerck units (mMU)/mL, respectively. Because the objective was to demonstrate antibody persistence at 14 years following vaccination in susceptible individuals, Cohort 2 was not included in the analysis.