Evaluating Distribution of a Tenofovir Douche With Tap Water Douching and Simulated Receptive Anal Intercourse (DREAM-02)
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|ClinicalTrials.gov Identifier: NCT04195776|
Recruitment Status : Not yet recruiting
First Posted : December 12, 2019
Last Update Posted : January 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|HIV/AIDS HIV Prevention||Drug: Tenofovir Douche||Phase 1|
DREAM-02 is proposed as the next step in the development of an on demand, behaviorally-congruent rectal tenofovir (TFV) microbicide to prevent HIV acquisition via unprotected receptive anal intercourse (RAI).
The DREAM Program has previously established that (1) no TFV pro-drug provides significantly superior colon tissue pharmacokinetics in pre-clinical models (mice and macaques), (2) a single rectal TFV douche protects macaques from repeated low dose rectal simian/human immunodeficiency virus (SHIV) challenge and is superior to oral daily dosing of TFV disoproxil fumarate (TDF), (3) it takes only 1-3 hours for a single 125 mL hypotonic rectal douche with a concentration of 5.28 mg/mL of TFV (660 mg total)to exceed by 100-fold the steady-state colon tissue TFV diphosphate (TFV-DP) concentrations associated with >90% protection (83 femtomoles/ million [fmol/106] Mucosal Mononuclear Cells (MMC) in oral daily dosing studies), and (4) DREAM behavioral survey research indicates very common use of one to several rectal douches in series prior to Unprotected Receptive Anal Intercourse (URAI).
DREAM-02 will assess the safety and PK of different sequences of administration of tap water (H2O) and rectal TFV douches to more accurately represent the community practice of commonly using cleansing douches prior to RAI, and occasionally after RAI, based on investigators' DREAM behavioral survey results. DREAM-02 results are essential to gain understanding of TFV-DP concentrations at various distances from the anal verge, and how those concentrations may be modified by sRAI, seminal fluid, and sequence of cleansing tap water douches.
The sequences of douche administration are selected to evaluate the impact of either a TFV rectal douche or H2O douche administered prior to, or following simulated sexual intercourse with ejaculation. The first sequence of administration will replicate administration of the dose that achieved the greatest tissue TFV-DP concentrations in DREAM-01 (660 mg TFV in 125 mL half-normal saline; TFV 5.28 mg/mL), then followed by simulated receptive anal intercourse (sRAI) and administration of autologous seminal fluid via a catheter embedded in an artificial phallus (Sequence A). Sequence B will evaluate the administration of the TFV rectal douche administered prior to sRAI and ejaculation followed by a cleansing H2O douche. Lastly, Sequence C will evaluate the administration of a cleansing H2O douche prior to sRAI and ejaculation followed by the TFV rectal douche.
Investigators hypothesize that douching after sex will increase the distribution of HIV surrogates within the lower GI tract and may lead to a mismatch of drug and HIV surrogate distribution, possibly, reducing rectal douche effectiveness. This information will be essential to the design of phase 2 extended safety studies of investigators' TFV douche, especially with regard to providing guidance for research participants and study counselors. Since DREAM-02 and DREAM-03 will use the same TFV douche product, DREAM-02 will provide data complementary to the 3 dose sequences planned for DREAM-03, and in the first arm of this protocol replicates the same product/conditions as used in the highest dose escalation step of DREAM-01, but with the addition of sRAI and exposure to autologous seminal fluid. Therefore, bridging data from DREAM-01, DREAM-02, and DREAM-03, as well as data from other DREAM Projects will inform the design and labeling of an optimal TFV douche for further clinical testing.
It is anticipated that the study will take approximately six months to complete study enrollment, and that each participant will be in the study for approximately six months from the time of screening.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Open Label Study Evaluating the Distribution of a Tenofovir Douche in Combination With Tap Water Douching and Simulated Receptive Anal Intercourse (DREAM-02)|
|Estimated Study Start Date :||March 2020|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||June 30, 2020|
Experimental: Three TFV Medicated Douche Sequences
Once enrolled, participants will complete a baseline sampling session and then three sequences of study product administration, along with sRAI and administration of autologous seminal fluid. Sequence A will be 1 TFV douche followed by sRAI; Sequence B will be one dose of TFV douche followed sRAI then a tap water douche; Sequence C will be 1 tap water douche followed sRAI then by a single dose of TFV douche. There will be a washout period of at least 14 days between sequences. Participants will have sequences administered in clinic or a research unit, followed by imaging and various specimen collections over 8 hours.
Drug: Tenofovir Douche
660 mg TFV in 125 mL hypo-osmolar solution
Other Name: TFV 660 mg in hypo-osmolar solution
- Change in Tenofovir Diphosphate (TFV-DP) concentration [ Time Frame: Approximately 6 months from the time of enrollment ]Colonic tissue cell TFV-DP concentrations (femtomoles/million cells) will be measured 3 hours after each study douche sequence administration.
- Anatomic distribution of radiolabeled Tenofovir douche [ Time Frame: Approximately 6 months from the time of enrollment ]Tenofovir douches will be radiolabeled with 111In-diethylenetriaminepentaacetic acid (DTPA) Computed tomography (CT) and single photon emission computed tomography (SPECT) imaging will be used at 1 hour after each TFV douche sequence administration to study the distribution of radiolabeled products. Maximal extent of radiosignal distribution from the anal verge, measured in centimeters (cm), will be estimated for each research participant and paired comparisons made between each dosing sequence.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04195776
|Contact: Margaret Chahoudemail@example.com|
|Contact: Jennifer Breakey, RN, MPHfirstname.lastname@example.org|
|Principal Investigator:||Edward Fuchs, PA-C||Johns Hopkins University|