Committee seeks stronger trial design, urging SII to sharpen objectives and raise scientific standards for proving CERVAVAC’s non-inferiority to Merck’s Gardasil
India’s expert committee on vaccines has asked the Serum Institute of India (SII) to revise its Phase III trial plan before moving ahead with tests of its cervical cancer vaccine in women of childbearing age. The vaccine is currently approved only for girls and young women aged 9 to 26 years.
The committee has suggested key changes in the study design, including strengthening the trial’s objectives and tightening the scientific criteria for proving non-inferiority against Merck’s Gardasil.
The Pune-based vaccine maker had presented the protocol of its proposed study titled, “A Phase-III, double-blind, randomized, active-controlled, multicentric clinical trial to evaluate the immunogenicity and safety of qHPV Vaccine (CERVAVAC) administered intramuscularly in women aged 27 to 45 Years as compared to Merck’s HPV 6/11/16/18 Vaccine (Gardasil).”
According to the minutes of the meeting of the subject expert committee (SEC), seen by News18, “the study vaccine is already approved in the age group of 9-14 years (male and female), at two-doses schedule (0 and 6 months) and for age group of 15-26 years (male and female), at three-dose schedule (0, 2 and 6 months) for prevention of the disease caused by Human Papilloma Virus types 6, 11, 16 and 18.”
CERVAVAC, developed by the Serum Institute in collaboration with the Department of Biotechnology, is India’s first indigenously made quadrivalent HPV vaccine, protecting against HPV types 6, 11, 16, and 18—the strains responsible for the majority of cervical cancer cases. If approved for the expanded age group, the vaccine could mark a significant step in widening India’s cervical cancer prevention programme.
What is the main goal?
The main goal of the study is to show that women who get CERVAVAC develop an immune response against Human Papillomavirus (HPV) types 16 and 18 that is just as strong as the response seen in women who get Merck’s Gardasil. A secondary goal is to check if the immune response against HPV types 6 and 11 with this vaccine is also as good as that with Gardasil.
According to the proposal, “the primary objective of the present study is to demonstrate that the immune response to HPV types 16 and 18 among women receiving CERVAVAC is non-inferior to that in the women receiving Gardasil and one of the secondary objectives is to demonstrate that the immune response to HPV types 6 and 11 among women receiving CERVAVAC is non-inferior to that in the women receiving Gardasil.”
However, the panel has advised the company to strengthen the trial by upgrading some of the study goals. It said that checking how well the vaccine triggers an immune response against HPV types 6 and 11 should be treated as a main goal of the study, not just a side one. It also advised the company to measure how well the vaccine protects women from long-lasting HPV infections (types 6, 11, 16, and 18) at 24 and 36 months, and to count this as an important study goal, not just an optional or exploratory part. “The firm should include determination of immune response to HPV types 6 and 11 as primary objective instead of secondary objective,” it recommended.
It also said the company should “consider assessing the protection against incident persistent cervical HPV 6, 11, 16 and 18 infections in women receiving CERVAVAC and Gardasil at 24, 36 months as secondary objective instead of exploratory objective for serotypes 6 and 11 infections.”
