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

Cervical Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00923702
• Other study ID #: BMGF48979
• Secondary ID: ISRCTN98283094RE
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: September 2009
• Est. completion date: July 2026

Study information

• Verified date: September 2023
• Source: International Agency for Research on Cancer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 22729
• Est. completion date: July 2026
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 10 Years to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Cervical Precancerous Lesions
• Uterine Cervical Neoplasms

Intervention

Biological:
• Prophylactic quadrivalent HPV vaccine Merck (Gardasil®)
The participants received either one, two or three doses of the avaccine. Each injection contains 20 microgram type 6, 40 microgram type 11, 40 microgram type 16, and 20 microgram type 18.

Locations

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

Sponsors (11)

Lead Sponsor

Collaborator

Partha Basu

All India Institute of Medical Sciences, New Delhi, Cancer Foundation of India, Christian Fellowship Community Health Centre, Deutsches Krebsforschungszentrum (DKFZ), Gujarat Cancer & Research Institute, Jehangir Clinical Development Centre, MNJ Institute of Oncology & Regional cancer Center, Rajiv Gandhi Centre for Biotechnology, Tata Memorial Centre, Tata Memorial Centre Rural Cancer Project, Nargis Dutt Memorial Cancer Hospital

Country where clinical trial is conducted

India, 

References & Publications (6)

Basu P, Malvi SG, Joshi S, Bhatla N, Muwonge R, Lucas E, Verma Y, Esmy PO, Poli URR, Shah A, Zomawia E, Pimple S, Jayant K, Hingmire S, Chiwate A, Divate U, Vashist S, Mishra G, Jadhav R, Siddiqi M, Sankaran S, Prabhu PR, Kannan TPRA, Varghese R, Shastri SS, Anantharaman D, Gheit T, Tommasino M, Sauvaget C, Pillai MR, Sankaranarayanan R. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study. Lancet Oncol. 2021 Nov;22(11):1518-1529. doi: 10.1016/S1470-2045(21)00453-8. Epub 2021 Oct 8. Erratum In: Lancet Oncol. 2022 Jan;23(1):e16. — View Citation

Basu P, Muwonge R, Bhatla N, Nene BM, Joshi S, Esmy PO, Poli URR, Joshi G, Verma Y, Zomawia E, Shastri SS, Pimple S, Anantharaman D, Prabhu PR, Hingmire S, Sauvaget C, Lucas E, Pawlita M, Gheit T, Jayant K, Malvi SG, Siddiqi M, Michel A, Butt J, Sankaran — View Citation

Bhatla N, Nene BM, Joshi S, Esmy PO, Poli URR, Joshi G, Verma Y, Zomawia E, Pimple S, Prabhu PR, Basu P, Muwonge R, Hingmire S, Sauvaget C, Lucas E, Pawlita M, Gheit T, Jayant K, Malvi SG, Siddiqi M, Michel A, Butt J, Sankaran S, Kannan TPRA, Varghese R, — View Citation

Muwonge R, Basu P, Gheit T, Anantharaman D, Verma Y, Bhatla N, Joshi S, Esmy PO, Poli URR, Shah A, Zomawia E, Shastri SS, Pimple S, Prabhu PR, Hingmire S, Chiwate A, Sauvaget C, Lucas E, Malvi SG, Siddiqi M, Sankaran S, Kannan TPRA, Varghese R, Divate U, — View Citation

Sankaranarayanan R, Joshi S, Muwonge R, Esmy PO, Basu P, Prabhu P, Bhatla N, Nene BM, Shaw J, Poli URR, Verma Y, Zomawia E, Pimple S, Tommasino M, Pawlita M, Gheit T, Waterboer T, Sehr P, Pillai MR; Indian HPV vaccine study group. Can a single dose of hum — View Citation

Sankaranarayanan R, Prabhu PR, Pawlita M, Gheit T, Bhatla N, Muwonge R, Nene BM, Esmy PO, Joshi S, Poli UR, Jivarajani P, Verma Y, Zomawia E, Siddiqi M, Shastri SS, Jayant K, Malvi SG, Lucas E, Michel A, Butt J, Vijayamma JM, Sankaran S, Kannan TP, Varghe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Florescent Intensities (MFI) of the Total Antibodies to Vaccine-included HPV Types (16/18/6/11) at Different Time Points	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.	Month 7 (for 3-dose and 2-dose groups), 12 (for 2 doses by default and single-dose groups), 18, 36, 48
Primary	Frequency of Persistent HPV 16/18/6/11 Infection.	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.	From date of marriage through to 7 years of follow-up
Primary	Frequency of HPV 16/18-associated Precancerous Lesions and Cancer.	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.	Cervical samples for HPV testing collected from married participants at the age of 25 and at 5 years after the first screen
Secondary	Frequency of Infection by Other Non-targeted High-risk HPV Types.	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.	Cervical samples for HPV testing collected from married participants at the age of 25 and at 5 years after the first screen
Secondary	Frequency of Cervical Neoplasia Associated With Non-included HPV Types.	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.	15 years from the base-line date