Simon Dobson BC Childrens Hospital Vaccine Evaluation Centre Child & Family Research Institute Vancouver University of British Columbia, Canada Two dose.

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