1. Two dose Q-HPV Vaccine Study
Simon Dobson
BC Children’s Hospital
Vaccine Evaluation Centre
Child & Family Research Institute
Vancouver
University of British Columbia, Canada

2. Disclosures I have carried out vaccine clinical trials for: Merck
GlaxoSmithkline
Novartis
Sanofi Pasteur
Dynavax
I have been on Advisory Boards for GlaxoSmithkline and Merck
I have been on the National Advisory Committee on Immunization (Canada)

3. 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

4. Why do this study?
Pre-licensure studies showed that 9-13 year olds responded better to the vaccine than year olds
Would it be possible to use this better response as an opportunity to use two instead of three doses?

5. Study Funded by: British Columbia Ministry of Health The Provincial Governments of Quebec and Nova Scotia

6. Control arms, Gardasil™
Trial design 2 dose versus 3 dose HPV vaccine study: a phase III post licensure randomized controlled trial
Sample Size N=825
Study group 1
9-13 year olds females
N=260
Study group 2
9-13 year old females
N=260
Study group 3
16-26 year olds females
N=305
Blinded outcome assessment
Study arm, Gardasil™
0 and 6 months
Control arms, Gardasil™
0, 2 and 6 months
Primary outcome: Anti-HPV 16 and 18 GMT, t = 7 months 6 6

7. Primary 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
Take GMT of intervention group and compare to reference group (959 mMU/L divided by 575 mMU/L = 1.67 with a 95% CI of
Lower end of the 95% CI was greater than 0,5 (1.46) therefore the intervention arm is deemed to be non-inferior 7

8. Geometric Mean Titres in the Intention To Treat Population
Dobson S et al. JAMA 2013

9. GMT Ratios in the Intention To Treat Population
Dobson s et al. JAMA 2013

10. Conclusions
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

11. GMT Ratios in the Intention To Treat Population
Dobson s et al. JAMA 2013

12. Why is this important? Better use of resources Protects more girls
Worldwide, saves lives

13. 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 schedules are also possible