Clinical trial NCT00923702: Trial of Two Versus Three Doses of Human Papillomavirus (HPV) Vaccine in India
Official title: Randomised Trial of Two Versus Three Doses of Human Papillomavirus (HPV) Vaccine in India
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Cervical Cancer
Cervical Precancerous Lesions
Lead sponsor: International Agency for Research on Cancer
Sponsor class: OTHER
Collaborators: name: All India Institute of Medical Sciences
name: Cancer Foundation of India
name: Christian Fellowship Community Health Centre
name: German Cancer Research Center
name: Gujarat Cancer & Research Institute
name: Jehangir Clinical Development Centre
name: MNJ Institute of Oncology and Regional Cancer Center
name: Rajiv Gandhi Centre for Biotechnology
name: Nargis Datta Memorial Cancer Hospital
name: Tata Memorial Centre
First posted: 2009-06-18
Enrollment: 22729
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median Florescent Intensities (MFI) of the Total Antibodies to Vaccine-included HPV Types (16/18/6/11) at Different Time Points
timeFrame: Month 7 (for 3-dose and 2-dose groups), 12 (for 2 doses by default and single-dose groups), 18, 36, 48
measure: Frequency of Persistent HPV 16/18/6/11 Infection.
timeFrame: From date of marriage through to 7 years of follow-up
measure: Frequency of HPV 16/18-associated Precancerous Lesions and Cancer.
timeFrame: Cervical samples for HPV testing collected from married participants at the age of 25 and at 5 years after the first screen
Secondary outcomes:
measure: Frequency of Infection by Other Non-targeted High-risk HPV Types.
timeFrame: Cervical samples for HPV testing collected from married participants at the age of 25 and at 5 years after the first screen
measure: Frequency of Cervical Neoplasia Associated With Non-included HPV Types.
timeFrame: 15 years from the base-line date
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: MNJ Institute of Oncology & Regional Cancer Center
state: Andhra Pradesh
city: Kolkata
country: India
facility: Cancer Foundation of India
state: Bengal
city: Ahmedabad
country: India
facility: Gujarat Cancer & Research Institute (GCRI)
state: Gujarat
city: Barshi
country: India
facility: Tata Memorial Centre Rural Cancer Project, Nargis Dutt Memorial Cancer Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Tata Memorial Center, Tata Memorial Hospital & Cancer Research Inst
state: Maharashtra
city: Pune
country: India
facility: Jehangir Clinical Development Centre (JCDC) Pvt. Ltd.
state: Maharashtra
city: Ambilikkai
country: India
facility: Christian Fellowship Community Health Centre
state: Tamil Nadu
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
Study officials:
affiliation: International Agency for Research on Cancer
name: Partha Basu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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, Varghese R, Divate U, Thomas S, Joshi G, Willhauck-Fleckenstein M, Waterboer T, Muller M, Sehr P, Hingmire S, Kriplani A, Mishra G, Pimple S, Jadhav R, Sauvaget C, Tommasino M, Pillai MR; Indian HPV Vaccine Study Group. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. Lancet Oncol. 2016 Jan;17(1):67-77. doi: 10.1016/S1470-2045(15)00414-3. Epub 2015 Dec 2.
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 human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study. Vaccine. 2018 Aug 6;36(32 Pt A):4783-4791. doi: 10.1016/j.vaccine.2018.02.087. Epub 2018 Mar 15.
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, Divate U, Willhauck-Fleckenstein M, Waterboer T, Muller M, Sehr P, Kriplani A, Mishra G, Jadhav R, Thorat R, Tommasino M, Pillai MR, Sankaranarayanan R; Indian HPV vaccine study group. Are two doses of human papillomavirus vaccine sufficient for girls aged 15-18 years? Results from a cohort study in India. Papillomavirus Res. 2018 Jun;5:163-171. doi: 10.1016/j.pvr.2018.03.008. Epub 2018 Mar 22.
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 S, Rameshwari Ammal Kannan TP, Varghese R, Divate U, Willhauck-Fleckenstein M, Waterboer T, Muller M, Sehr P, Vashist S, Mishra G, Jadhav R, Thorat R, Tommasino M, Pillai MR, Sankaranarayanan R; Indian HPV vaccine study group. Two-dose recommendation for Human Papillomavirus vaccine can be extended up to 18 years - updated evidence from Indian follow-up cohort study. Papillomavirus Res. 2019 Jun;7:75-81. doi: 10.1016/j.pvr.2019.01.004. Epub 2019 Jan 31.
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, Vashist S, Mishra G, Jadhav R, Tommasino M, Pillai MR, Sankaranarayanan R, Jayant K; Indian HPV vaccine study group. Acquisition, prevalence and clearance of type-specific human papillomavirus infections in young sexually active Indian women: A community-based multicentric cohort study. PLoS One. 2020 Dec 29;15(12):e0244242. doi: 10.1371/journal.pone.0244242. eCollection 2020.