Trial of Two Versus Three Doses of Human Papillomavirus (HPV) Vaccine in India

Phase 4

Active, not recruiting

Conditions: Cervical Cancer
Cervical Precancerous Lesions

Interventions: Biological: Prophylactic quadrivalent HPV vaccine Merck (Gardasil®)

Registration Number: NCT00923702

Lead Sponsor: Partha Basu

Brief Summary: The primary study hypothesis wasthat a two-dose human papillomavirus (HPV) vaccine regimen would offer similar immunogenicity and protection as that of a three-dose regimen to girls against persistent HPV infection and cervical neoplasia caused by HPV types included in the vaccine. The Government of India stopped vaccination in all the HPV vaccine trials in the country in April 2010 due to reasons not related to this study.

Detailed Description: The suspension of vaccination resulted in girls receiving 3 doses (days 1, 60 and ≥180), receiving 2 doses (days 1 and ≥180), receiving 2 doses at days 1 and 60 due to incomplete treatment ("by default"), and receiving one dose by default. A first age and site-matched cohort of unvaccinated married women was recruited, starting in May 2012 to serve as the unvaccinated control group of women for the analysis of HPV incidence and persistence outcomes. A second age and site-matched (age and site matched to the vaccinated women undergoing screening) cohort of unvaccinated married women is being recruited starting in June 2017 and is to be used in addition to the first unvaccinated cohort for the assessment of the cervical neoplasia outcome.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Female

Target Recruitment: 22729

Inclusion Criteria

Apparently healthy, ambulant girls aged 10 - 18 years
Unmarried girls
Girls with intact uterus
Resident in the villages chosen for the study

Exclusion Criteria

Girls with any severe and/or debilitating illness
Past history of allergy to any medication

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
3-dose	Prophylactic quadrivalent HPV vaccine Merck (Gardasil®)	The participants received three doses of the Prophylactic quadrivalent HPV vaccine Merck (Gardasil®) at days 1, 60 and 180+.
2-dose	Prophylactic quadrivalent HPV vaccine Merck (Gardasil®)	The participants received two doses of the Prophylactic quadrivalent HPV vaccine Merck (Gardasil®) at days 1 and 180+.
Single-dose	Prophylactic quadrivalent HPV vaccine Merck (Gardasil®)	The participants received one dose of the Prophylactic quadrivalent HPV vaccine Merck (Gardasil®) by default (incomplete doses)
2 doses by default	Prophylactic quadrivalent HPV vaccine Merck (Gardasil®)	The participants received two doses of the Prophylactic quadrivalent HPV vaccine Merck (Gardasil®) at days 1 and 60 by default (incomplete doses)

Primary Outcome Measures

Name	Time	Method
Frequency of HPV 16/18-associated Precancerous Lesions and Cancer.	Cervical samples for HPV testing collected from married participants at the age of 25 and at 5 years after the first screen	Pathology Panel diagnosis of: CIN 2, CIN 3 (including squamous carcinoma in situ), adenocarcinoma in situ, invasive squamous cervical carcinoma, or invasive adenocarcinoma of the cervix and detection of HPV 16 and/or HPV 18 by PCR in the same biopsy tissue sample.
Median Florescent Intensities (MFI) of the Total Antibodies to Vaccine-included HPV Types (16/18/6/11) at Different Time Points	Month 7 (for 3-dose and 2-dose groups), 12 (for 2 doses by default and single-dose groups), 18, 36, 48	Samples were treated with EDTA and analysed with Luminex (Austin, TX, USA) based multiplex serology to assess the concentration of binding antibodies against the major capsid protein L1 as mean median fluorescence intensity (MFI). MFI values as a measure of antibody concentration quantified by use of HPV multiplex serology are directly comparable with optical densities measured with ELISA.
Frequency of Persistent HPV 16/18/6/11 Infection.	From date of marriage through to 7 years of follow-up	The first cervical cell samples were collected from women 18 months after married or 6 months after the first delivery. After that, 3 extra annual collections were obtained. The HPV genotyping method involved HPV-type-specific E7 PCR bead-based multiplex genotyping. The multiplex HPV-type-specific E7 PCR uses HPV type-specific primers targeting the E7 region for the detection of 19 high-risk or probable high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68a, 68b, 70, 73, and 82), and two low-risk HPV types (6 and 11), with detection limits ranging from ten to 1000 copies of the viral genome.

Secondary Outcome Measures

Name	Time	Method
Frequency of Cervical Neoplasia Associated With Non-included HPV Types.	15 years from the base-line date	Pathology Panel diagnosis of: CIN 2, CIN 3 (including squamous carcinoma in situ), adenocarcinoma in situ, invasive squamous cervical carcinoma, or invasive adenocarcinoma of the cervix and detection of other non vaccine included HPV types by PCR in the same biopsy tissue sample.
Frequency of Infection by Other Non-targeted High-risk HPV Types.	Cervical samples for HPV testing collected from married participants at the age of 25 and at 5 years after the first screen	The HPV genotyping method involved HPV-type-specific E7 PCR bead-based multiplex genotyping. The multiplex HPV-type-specific E7 PCR uses HPV type-specific primers targeting the E7 region for the detection of 19 high-risk or probable high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68a, 68b, 70, 73, and 82), and two low-risk HPV types (6 and 11), with detection limits ranging from ten to 1000 copies of the viral genome.

Trial Locations

Locations (8): All India Institute of Medical Sciences
🇮🇳
New Delhi, India
Tata Memorial Center, Tata Memorial Hospital & Cancer Research Inst
🇮🇳
Mumbai, Maharashtra, India
MNJ Institute of Oncology & Regional Cancer Center
🇮🇳
Hyderabad, Andhra Pradesh, India
Cancer Foundation of India
🇮🇳
Kolkata, Bengal, India
Jehangir Clinical Development Centre (JCDC) Pvt. Ltd.
🇮🇳
Pune, Maharashtra, India
Gujarat Cancer & Research Institute (GCRI)
🇮🇳
Ahmedabad, Gujarat, India
Tata Memorial Centre Rural Cancer Project, Nargis Dutt Memorial Cancer Hospital
🇮🇳
Barshi, Maharashtra, India
Christian Fellowship Community Health Centre
🇮🇳
Ambilikkai, Tamil Nadu, India