Simon Dobson
BC Children’s Hospital
Vaccine Evaluation Centre
Child & Family Research Institute
Vancouver
University of British Columbia, Canada
Two dose Q-HPV Vaccine Study
DisclosuresDisclosures
• I have carried out vaccine clinical trials for:I have carried out vaccine clinical trials for:– MerckMerck– GlaxoSmithklineGlaxoSmithkline– NovartisNovartis– Sanofi PasteurSanofi Pasteur– DynavaxDynavax
• I have been on Advisory Boards for GlaxoSmithkline and MerckI have been on Advisory Boards for GlaxoSmithkline and Merck
• I have been on the National Advisory Committee on Immunization I have been on the National Advisory Committee on Immunization (Canada)(Canada)
Why do this study?
• Cervical cancer is second most common cancer in women worldwide (500,000 per year)
• HPV vaccines offer the opportunity of primary prevention
• Barriers are vaccine cost and accessibility
Why do this study?
• Pre-licensure studies showed that 9-13 year olds responded better to the vaccine than 16-26 year olds
• Would it be possible to use this better response as an opportunity to use two instead of three doses?
Study Funded by:Study Funded by:
British Columbia Ministry of HealthBritish Columbia Ministry of HealthThe Provincial Governments of Quebec and Nova The Provincial Governments of Quebec and Nova
ScotiaScotia
6
Trial designTrial design 2 dose versus 3 dose HPV vaccine study: a phase III post 2 dose versus 3 dose HPV vaccine study: a phase III post
licensure randomized controlled triallicensure randomized controlled trial
Sample Size N=825
Study arm, Gardasil™ 0 and 6 months
Control arms, Gardasil™ 0, 2 and 6 months
Study group 19-13 year olds
femalesN=260
Study group 316-26 year olds
femalesN=305
Primary outcome: Anti-HPV 16 and 18 GMT, t = 7 months
Study group 29-13 year old
femalesN=260
Primary EndpointsPrimary Endpoints
• Differences in Geometric Mean Titres (GMT) of antibodies to HPV 16 and HPV 18 at Month 7
• Non-inferiority will be declared if lower bounds of the adjusted 95% CI of GMT ratios for HPV 16 and HPV 18 are greater than 0.5
Geometric Mean Titres in the Intention To Treat Population
Dobson S et al. JAMA 2013
GMT Ratios in the Intention To Treat Population
Dobson s et al. JAMA 2013
ConclusionsConclusions
• Following a 2 dose regimen in 9-13 year old girls, antibody responses to HPV-16,-18,-6,-11 were non-inferior through 36 months, as compared to a 3-dose regimen in young adult women
GMT Ratios in the Intention To Treat Population
Dobson s et al. JAMA 2013
Why is this important?
• Better use of resources
• Protects more girls
• Worldwide, saves lives
But….. Still need answers to two questions:
• What is the duration of protection?
– This is known for neither 3 doses nor 2 doses…yet
• Does 2 doses work as well as 3 doses?
– A Canadian study has started
Extended 2 + 1 schedules are also possible