Rectal Microbicides: Where We’re Heading - PowerPoint Presentation

Slide1

Rectal Microbicides: Where We’re Heading

Craig Hendrix, MDJohns Hopkins UniversityMicrobicide Trial NetworkSlide2

Rectal Microbicide Need

Oral PrEP not for everyonePrevention options improve overall adherenceContraceptive development experienceDesire 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 gelSlide3

Rectal Microbicide Feasibility

On demand oral PrEP (Truvada) efficacy highIpergay 86 % risk reductionOn 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 & adherenceSlide4

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 …Slide5

…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!)Slide6

MTN-026 Study

Phase 1 rectal safety, acceptability, and PK/PD evaluation of 0.05% dapivirine gelDapivirine proven efficacy in women (vaginal ring)Men and women (cis and transgender) (N=27)Clinical sitesPittsburgh and BirminghamSlide7

MTN-033 Study

Phase 1 evaluation of dapivirine gel as lubeCompare application of gel as sexual lubricant (using phallus & simulated anal sex) to applicator dosing of gelMSM 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

DPV gel (10.0 g)

Phallic device

DPV

gel (2.5 g)

ApplicatorSlide8

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 developmentSlide9

MTN-037 Study

MIV-150 / Carrageenan / Zinc gelActive against HIV, HSV, & HPV in lab & animal studiesMen and women (cis and transgender) (N=24)Study Design

Single dose of gelDose escalation from 4 mL to 32 mL of gelSafety, acceptability, drug concentration, tissue protectionSlide10

MTN-039 Study

Phase 1 rectal insertActive ingredient: Elvitegravir (integrase inhibitor licensed for treatment)

Safety, acceptability, drug tissue concentration, biopsy susceptibility to infectionCONRAD collaboration

Men and women (cis and transgender) (N = 20)Single dose studySlide11

DREAM Program

On demand rectal douche as “behaviorally-congruent” rectal microbicide

DREAM 01 Clinical Study– Single

ascending dose studyEach of 16 participants receives a series of 3 enemas, gradually increasing doseAssess safety, acceptability, drug concentration, susceptibility of colon biopsies to infection

UCLA

, Pitt, & JHU

PI: Craig Hendrix Johns Hopkins UniversitySlide12

ImQuest Program

DuoGel: Dual Compartment (Rectal & Vaginal) GelActive Ingredient: IQP-0528 Non-nucleoside reverse transcriptase inhibitorClinicalFirst-in-Human Phase 1, Single rectal dose

8 men & 8 womenSafety, drug concentration, biopsy susceptibility to infection, acceptability

Enrolling now at Johns Hopkins University

PI: Robert Buckheit, Jr., ImQuest BioSciences, Inc.Slide13

PREVENT Program

Development of Griffithsin (GRFT) rectal microbicideGRFT has activity against HIV, HSV, and HCVPreclinical program

NHP studies ongoingPhase 1 study University of Pittsburgh

Scheduled for 2018

Griffithsin rectal gel

PI: Kenneth Palmer, University of Louisville Slide14

√

completed study; √

Phase 2; Estimated start-completion dates for

Enrolling & Planned studies

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

0

6/18-02/20

MTN-035

06/18-02/20

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

01/18-05/19ElvitegravirMTN-03905/18-07/19IQP-0528ImQuest 0208/17-10/18GriffithsinPREVENT2018-2019

Behaviorally-

Congruent

On Demand

Multi-purpose STI

Vaginal & Rectal

All by Q1 2020Slide15

Conclusions

Rectal microbicide promise based on tenofovir success:On demand Ipergay, vaginal microbicide efficacy, animal studiesCommunity remains supportive of rectal microbicides

Desire for on demand rectal microbicidePreferably 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 2020Slide16

Thank You!Slide17

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.