NCT00923702

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

Active, enrolled Phase 4 Results posted Last updated 27 September 2023

What this trial tests

Phase 4 trial testing Prophylactic quadrivalent HPV vaccine Merck (Gardasil®) in Cervical Cancer in 22,729 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

1 September 2009

Primary endpoint
1 January 2017

1 July 2026

Quick facts

Lead sponsor	Partha Basu
Phase	Phase 4
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	22,729
Start date	1 September 2009
Primary completion	1 January 2017
Estimated completion	1 July 2026
Sites	8 locations across India

Drugs / interventions tested

• Prophylactic quadrivalent HPV vaccine Merck (Gardasil®) — full drug profile →

Conditions studied

• Cervical Cancer — all drugs for Cervical Cancer →
• Cervical Precancerous Lesions — all drugs for Cervical Precancerous Lesions →

Sponsor

Partha Basu — full company profile →

Who can join

Adults 10 to 18, female only, with Cervical Cancer or Cervical Precancerous Lesions. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Median Florescent Intensities (MFI) of the Total Antibodies to Vaccine-included HPV Types (16/18/6/11) at Different Time Points
  Time frame: 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.
  Time frame: 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 pr
• Frequency of HPV 16/18-associated Precancerous Lesions and Cancer.
  Time frame: 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.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study.
   Sankaranarayanan R, Prabhu PR, Pawlita M, Gheit T, et al · · 2016 · cited 189× · PMID 26652797 · DOI 10.1016/s1470-2045(15)00414-3
2. 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.
   Basu P, Malvi SG, Joshi S, Bhatla N, et al · · 2021 · cited 184× · PMID 34634254 · DOI 10.1016/s1470-2045(21)00453-8
3. Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.
   Sankaranarayanan R, Joshi S, Muwonge R, Esmy PO, et al · · 2018 · cited 124× · PMID 29551226 · DOI 10.1016/j.vaccine.2018.02.087
4. Evaluation of immune response to single dose of quadrivalent HPV vaccine at 10-year post-vaccination.
   Joshi S, Anantharaman D, Muwonge R, Bhatla N, et al · · 2023 · cited 60× · PMID 36446654 · DOI 10.1016/j.vaccine.2022.11.044
5. Peak neutralizing and cross-neutralizing antibody levels to human papillomavirus types 6/16/18/31/33/45/52/58 induced by bivalent and quadrivalent HPV vaccines.
   Mariz FC, Bender N, Anantharaman D, Basu P, et al · · 2020 · cited 35× · PMID 32128255 · DOI 10.1038/s41541-020-0165-x
6. Alternative dosage schedules with HPV virus-like particle vaccines.
   Stanley MA, Sudenga SL, Giuliano AR. · · 2014 · cited 35× · PMID 25001893 · DOI 10.1586/14760584.2014.935767
7. Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.
   Arrossi S, Temin S, Garland S, Eckert LO, et al · · 2017 · cited 33× · PMID 29094100 · DOI 10.1200/jgo.2016.008151
8. Rationale and design of a double-blind randomized non-inferiority clinical trial to evaluate one or two doses of vaccine against human papillomavirus including an epidemiologic survey to estimate vaccine efficacy: The Costa Rica ESCUDDO trial.
   Porras C, Sampson JN, Herrero R, Gail MH, et al · · 2022 · cited 29× · PMID 34857420 · DOI 10.1016/j.vaccine.2021.11.041