Rectal Insert Safety Study

(RITE PrEP Trial)

Overseen By Karen Dominguez, MPH

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Eastern Virginia Medical School

Must not be taking: NSAIDs, Anticoagulants, Immunomodulators, others

Disqualifiers: Hepatitis, Kidney disease, Bowel disease, others

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new rectal insert treatment called TAF/EVG, developed to prevent HIV. Participants will receive either the active treatment or a placebo (a harmless substitute without the active drug) for a set period. The trial seeks individuals who have engaged in receptive anal intercourse and are HIV-negative. Participants should be comfortable with medical procedures like blood tests and biopsies. As an early-stage study, it focuses on understanding how the body processes the treatment and ensuring it causes no harm. In this Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop taking my current medications to join the trial?

Yes, you may need to stop certain medications. Specifically, you cannot use aspirin, NSAIDs, blood thinners, rectal medications, systemic immunomodulatory agents, high doses of steroids, experimental drugs, or certain enzyme inducers/inhibitors before and during the trial. Check with the study team for more details.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the TAF/EVG rectal insert is safe and well-tolerated. In one study, participants using the insert did not experience any serious side effects, confirming its safety as it did not cause major health issues. Another study found that the insert delivered high levels of medication to the rectal tissues while maintaining low levels in the rest of the body. This targeted delivery is beneficial as it focuses treatment on the intended area without significantly affecting the whole body.

Overall, previous testing has confirmed the TAF/EVG insert's safety for rectal use, which is encouraging for prospective trial participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TAF/EVG rectal inserts because they offer a novel delivery method for HIV prevention. Unlike traditional methods that typically involve daily oral pills, these rectal inserts provide a localized approach, potentially reducing systemic side effects and improving adherence. Additionally, TAF (tenofovir alafenamide) and EVG (elvitegravir) are active ingredients known for their effectiveness in HIV treatment, but this formulation aims to harness their power with less frequent dosing. This innovative strategy could make HIV prevention more accessible and user-friendly, especially for those who find daily pills challenging.

What evidence suggests that these rectal inserts could be effective?

Research has shown that TAF/EVG inserts effectively prevent HIV. Earlier studies demonstrated that these inserts reached high levels in rectal tissue, crucial for stopping the virus, while maintaining low levels in the blood, resulting in fewer side effects. Participants tolerated the inserts well. In this trial, participants will receive either the active TAF/EVG inserts or matching placebo inserts. This treatment shows promise in protecting against both vaginal and rectal infections. ^{2 4 6 7 8}

Who Is on the Research Team?

Cassie Grimsley Ackerley, MD, MSc

Principal Investigator

Emory School of Medicine

Richard E Haaland

Principal Investigator

Centers for Disease Control and Prevention

Gustavo F Doncel, MD, PhD

Principal Investigator

CONRAD

Are You a Good Fit for This Trial?

The RITE PrEP study is for individuals aged 18-59 who have a history of receptive anal intercourse, are HIV-negative, and can give informed consent. They must be willing to undergo various tests including blood, urine, and rectal biopsies. Women must agree to additional cervicovaginal secretion collection. Participants should not have bowel conditions that could worsen with the study or distort anatomy.

Inclusion Criteria

I am willing to provide blood, urine, rectal secretion samples, and undergo a rectal biopsy.

For participants of childbearing potential: Willing to use an effective method of contraception for at least 30 days prior to enrollment and for the duration of study participation. Effective methods include hormonal methods, intrauterine device (IUD) inserted at least 30 days prior to enrollment, sterilization (of participant or partner), being sexually abstinent as defined by abstaining from penile-vaginal intercourse for 90 days prior to enrollment and intending to remain abstinent for the duration of study participation, and willing to commit to using condoms for the duration of the study

I have had receptive anal intercourse in my life.

Exclusion Criteria

Significant laboratory abnormalities at baseline including but not limited to hemoglobin ≤ 10 g/dL, platelet count <100,000, Aspartate aminotransferase (AST) or alanine transaminase (ALT) >1.3x ULN, serum creatinine >1.3x upper limit of normal (ULN), PTT > 1.5x ULN or International normalized ratio (INR) >1.5x ULN

I have kidney disease or my kidney function is low.

I have a history of serious lower GI tract conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants self-administer two TAF/EVG or placebo rectal inserts for 3 consecutive days

1 week

3 visits (in-person) at 24, 48, and 72 hours after last dose

Washout

A washout period between study phases

1-4 weeks

Phase 2 Treatment

Participants administer two TAF/EVG or placebo rectal inserts every other day for 7 doses

2 weeks

4 visits (in-person) at 24, 48, 72 hours, and 7 days after final dose

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAF/EVG

Trial Overview This trial is testing the safety and how the body processes TAF/EVG rectal inserts compared to placebo inserts over several days. It's double-blind (neither researchers nor participants know who gets what), randomized (assigned by chance), and involves two phases with different dosing schedules.

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

2 TAF/EVG (20/16mg) rectal inserts

Group II: Placebo Placebo Group 1 Intervention

2 Matching placebo inserts

Who Is Running the Clinical Trial?

Eastern Virginia Medical School

Lead Sponsor

Trials

77

Recruited

16,500+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

CONRAD

Collaborator

Trials

60

Recruited

11,800+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38655842/

A Phase 1 Clinical Trial to Assess the Safety and ... - PubMed Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and ...

2. academic.oup.com academic.oup.com/jid/article/230/3/696/7657362

A Phase 1 Clinical Trial to Assess the Safety and ... TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9643401/

Pharmacokinetics and efficacy of topical inserts containing ... TAF/EVG inserts are a promising new HIV prevention modality that provides dual compartment protection against both vaginal and rectal infection. Compared to ...

4. natap.org natap.org/2023/CROI/croi_61.htm

Good Rectal TAF/EVG Levels With Rectal Inserts in HIV- ... Being studied for preexposure prophylaxis (PrEP), the inserts were safe and participants tolerated them well in this short study. These fast- ...

5. mpts101.org mpts101.org/taf-elvitegravir-topical-insert/

TAF / Elvitegravir Topical Insert The TAF/EVG insert dosed either vaginally (single dose) or rectally (double dose) provides strong protection against vaginal or rectal SHIV exposure.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04047420

NCT04047420 | Safety and Pharmacokinetic Study of ... This study will evaluate the safety and pharmacokinetics of rectal administration of a tenofovir alafenamide (TAF)/elvitegravir (EVG) insert at two dose ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11420810/

A Phase 1 Clinical Trial to Assess the Safety and ... In summary, the TAF/EVG insert administered rectally was safe and well tolerated, with favorable PK and ex vivo protection from HIV infection for up to 72 hours ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06274398

Study Details | NCT06274398 | Rectal Insert TAF/EVG Pre- ... The purpose of this study is to collect data regarding the safety and pharmacokinetics of repeat dosing schedules of TAF and EVG administered rectally to ...