Transcript Microbicides 2008

Looking Ahead to MTN-017
Ross D. Cranston MD, FRCP
Microbicide Trials Network
IRMA
Rationale: Key points

Unprotected receptive anal intercourse is a high risk
sexual activity for HIV transmission

We need products to prevent HIV through anal sex –
commonly practiced by both men and women around
the world

Animal studies and an early clinical study have shown
vaginal tenofovir gel has an anti-HIV effect when used
in the rectum

More information about the safety and acceptability of
tenofovir gel as a rectal microbicide is necessary to
move forward
MTN-017 protocol overview







Design and rationale
Study objectives
Participants and enrollment
Study procedures
Safety monitoring
Timelines
Questions and discussion
How MTN-017 is designed




Phase II trial evaluating safety and acceptability
Will include 186 men who have sex with men and transgender
women
Study regimens will include:

Rectal tenofovir gel used daily

Rectal tenofovir gel used before and after sex

Truvada tablets taken daily
Each participant will follow all of the study regimens for eight
weeks, with a weeklong break between regimens when no
product will be used


The order in which participants follow study regimens will be based on random
assignment
All participants will receive standard HIV prevention package
MTN-017 study design
Product
Sequence
Period 1
(8 weeks)
Product
Break
(1 week)
Period 2
(8 weeks)
Product
Break
(1 week)
Period 3
(8 weeks)
1
Daily Truvada
Daily rectal gel
Rectal gel before
and after sex
2
Rectal gel before
and after sex
Daily Truvada
Daily rectal gel
3
Daily rectal gel
Rectal gel before
and after sex
Daily Truvada
4
Daily rectal gel
Daily Truvada
Rectal gel before
and after sex
5
Daily Truvada
tablets
Rectal gel before
and after sex
Daily rectal gel
6
Rectal gel before
and after sex
Daily Rectal gel
Daily Truvada
About the study products


Rectal-friendly formulation of tenofovir gel
 Tenofovir gel for vaginal use modified to have less
glycerin
 Rectal-friendly formulation evaluated in MTN-007
Truvada tablets
 Brand name for combination drug containing
tenofovir and emtricitabine
 iPrEX study showed Truvada reduced the risk of
HIV infection among men who have sex with men
by nearly 44 percent when used daily compared a
placebo tablet
Primary objectives: Safety and
Acceptability


Compare the safety profiles of rectal
tenofovir gel used daily and before and after
sex, and Truvada tablets
Evaluate and compare the acceptability of
Truvada tablets to rectal tenofovir gel, i.e.,
did they like the product?; would they use it
in the future, if available?
Secondary objectives





Estimate adherence to the products, i.e. did they use
the product? (Examples: SMS, Computer Assisted
Self Interview, applicator/pill count)
Measure drug levels (blood and tissues)
Examine whether sexual activity or condom use
varies by product
Determine the level of product sharing with nonparticipants
Determine practices associated with anal sex that
could detract from microbicide effectiveness, i.e.
lubes, douching
Who can participate?


HIV-uninfected, men who have sex with
men and transgender women 18 and
older who have practiced receptive anal
intercourse within the last three months
Participants must also meet other
inclusion and exclusion criteria to ensure
they are in general good health
Study visits and procedures




Screening visit
 Informed consent
 Physical and rectal exams
 HIV risk reduction counseling
Enrollment visit
 Randomization of participants
Follow-up visits
 Monthly
Visit procedures
 Physical exams
 Rectal exams
 Urine and blood tests
 Rectal biopsies (flexible sigmoidoscopy) at some sites
 Behavioral surveys
MTN-017: Summary





First Phase II trial of a rectal microbicide for HIV
prevention through receptive anal sex
Seeks to answer whether tenofovir gel is safe and
acceptable as a rectal microbicide
Will involve 186 men who have sex with men and
transgender women at trial sites in South Africa, Peru,
Thailand and the United States
Designed to provide the safety data sufficient to move
forward with a large effectiveness study
Anticipated to begin mid 2012; results late 2013
Rectal microbicides timeline
2010 2011 2012 2013 2014 2015 2016 2017 2018
Phase I
(MTN-006/
MTN-007)
Phase II
(MTN-017)
Phase IIb
Review
Available
What’s next in our timeline?
March/April
2012
Mid 2012
• Finalize MTN-017 draft protocol
• MTN-017 PSRC review on April 3rd
• MTN-017 underway!
Acknowledgements
MTN is funded by NIAID (5U01AI068633),
NICHD and NIMH, all of the U.S. National
Institutes of Health
Thank You!