1. Rectal Microbicides: Where We’re Heading
Craig Hendrix, MD
Johns Hopkins University
Microbicide Trial Network

2. Rectal Microbicide Need
Oral PrEP not for everyone
Prevention options improve overall adherence
Contraceptive development experience
Desire for products that can be used around the time of sex (on demand)
Desire for products that conform to commonly practiced anal sex behaviors, e.g., a lube or douche (behaviorally-congruent) rather than using an applicator to deliver a gel

3. Rectal Microbicide Feasibility
On demand oral PrEP (Truvada) efficacy high
Ipergay 86 % risk reduction
On demand vaginal tenofovir efficacy modest
CAPRISA 004, FACTS 001 ~60% with good adherence
Animal models: rectal tenofovir protects from anal monkey HIV
Behaviorally-congruent formulations “piggy-back” onto common sexual practices to potentially improve uptake & adherence

4. Gaps in Knowledge
Will a lube, douche, suppository, or insert (tablet) be …
capable of delivering enough drug to the rectum?
acceptable for use before anal sex?
Can any drug protect both the rectum and vagina with one dose?
Do single doses before sex deliver enough drug?
Does any product protect from other STIs as well as HIV?
To address these key questions …

5. …The Rectal Road Continues
7 drugs, 4 formulations being tested as rectal microbicides in 8 studies
*5 MTN rectal microbicide studies being developed, 2 expected to launch in 2017
*3 Program Project grant studies ongoing or in development
…all funded by the NIH (Thank you!)

6. MTN-026 Study
Phase 1 rectal safety, acceptability, and PK/PD evaluation of 0.05% dapivirine gel
Dapivirine proven efficacy in women (vaginal ring)
Men and women (cis and transgender) (N=27)
Clinical sites
Pittsburgh and Birmingham

7. MTN-033 Study Phase 1 evaluation of dapivirine gel as lube
Compare application of gel as sexual lubricant (using phallus & simulated anal sex) to applicator dosing of gel
MSM and transgender women (N=16)
Outcome: Measure distribution of drug in colon tissue N
Period 1
Washout
Period 2
Sequence A 8
DPV gel (2.5 g)
Applicator
2-4 weeks
DPV gel (10.0 g)
Phallic device
Sequence B

8. MTN-035 Study
Acceptability, tolerability and adherence study (no active ingredient)
Placebo enema (douche), rectal insert (fast- dissolving tablet), & suppository
MSM and transgender women (N=210)
Design under development

9. MTN-037 Study MIV-150 / Carrageenan / Zinc gel
Active against HIV, HSV, & HPV in lab & animal studies
Men and women (cis and transgender) (N=24)
Study Design
Single dose of gel
Dose escalation from 4 mL to 32 mL of gel
Safety, acceptability, drug concentration, tissue protection

10. MTN-039 Study Phase 1 rectal insert Active ingredient: Elvitegravir
(integrase inhibitor licensed for treatment)
Safety, acceptability, drug tissue concentration, biopsy susceptibility to infection
CONRAD collaboration
Men and women (cis and transgender) (N = 20)
Single dose study

11. DREAM Program
On demand rectal douche as “behaviorally-congruent” rectal microbicide
DREAM 01 Clinical Study–
Single ascending dose study
Each of 16 participants receives a series of 3 enemas, gradually increasing dose
Assess safety, acceptability, drug concentration, susceptibility of colon biopsies to infection
UCLA, Pitt, & JHU
PI: Craig Hendrix Johns Hopkins University

12. ImQuest Program DuoGel: Dual Compartment (Rectal & Vaginal) Gel
Active Ingredient: IQP-0528 Non-nucleoside reverse transcriptase inhibitor
Clinical
First-in-Human Phase 1, Single rectal dose
8 men & 8 women
Safety, drug concentration, biopsy susceptibility to infection, acceptability
Enrolling now at Johns Hopkins University
PI: Robert Buckheit, Jr., ImQuest BioSciences, Inc.

13. Griffithsin rectal gel
PREVENT Program
Development of Griffithsin (GRFT) rectal microbicide
GRFT has activity against HIV, HSV, and HCV
Preclinical program
NHP studies ongoing
Phase 1 study
University of Pittsburgh
Scheduled for 2018
Griffithsin rectal gel
PI: Kenneth Palmer, University of Louisville

14. Study Timeline & Gaps Being Filled
Active Drug
Gel w/
Applicator
Gel as Lube
Douche
Insert
Suppository
Placebo
√√√√√ √
√, MTN-035
06/18-02/20
MTN-035
Tenofovir
√√√√√√
DREAM 01
11/16-4/18
Maraviroc
Dapivirine
MTN-026
09/17-12/18
MTN-033
12/17-01/19
MIV-150/Zn/CG
MTN-037
01/18-05/19
Elvitegravir
MTN-039
05/18-07/19
IQP-0528
ImQuest 02
08/17-10/18
Griffithsin
PREVENT
On Demand
Behaviorally-
Congruent
All by Q1 2020
Multi-purpose STI
Vaginal & Rectal
√ completed study; √ Phase 2; Estimated start-completion dates for Enrolling & Planned studies

15. Conclusions Rectal microbicide promise based on tenofovir success:
On demand Ipergay, vaginal microbicide efficacy, animal studies
Community remains supportive of rectal microbicides
Desire for on demand rectal microbicide
Preferably in a formulation already used before anal sex
In Response, 8 Rectal Microbicide studies
7 drugs, 4 formulations provide options to select best candidate for further safety & efficacy testing completed by 2020

16. Thank You!

17. Acknowledgements
The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from the Eunice Kennedy Shriver  National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the U.S. National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.