Craig Hendrix MD Johns Hopkins University Microbicide Trial Network Rectal Microbicide Need Oral PrEP not for everyone Prevention options improve overall adherence Contraceptive development experience ID: 718866
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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.