NCT02165202

Phase II Safety and Acceptability of an Investigational Injectable Product, TMC278LA, for Pre-Exposure Prophylaxis

HPTN 076 - Phase II Safety and Acceptability of an Investigational Injectable Product, TMC278 LA, for Pre-Exposure Prophylaxis (PrEP)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 136 (actual)
• Sponsor: PATH · Academic / Other
• Sex: Female
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This is a multi-site, double-blinded, two-arm, two:one, randomized, trial comparing the safety of an intramuscular (IM) injection of TMC278 LA to a placebo given once every eight weeks over a 40 week period among sexually active, HIV- uninfected women.

Detailed description

This is a multi-site, double-blinded, two-arm, two:one randomized, placebo-controlled trial comparing the safety of TMC278 LA for 48 weeks after the initial 1M injection to a saline (0.9%NaCI) placebo IM injection among sexually active, HIV-uninfected women who are assessed by the clinic staff as being at "low risk" for HIV acquisition (in keeping with a safety trial). Approximately 132 women will be randomized to TMC278 LA and placebo in approximately a two:one ratio (88 and 44 in the TMC278 LA and placebo arm, respectively). Approximately 96 women will be enrolled in SSA and approximately 36 women will be enrolled in the US. In order to screen for initial safety and tolerability of the active product, a run-in period with oral rilpivirine will precede the injection of TMC278 LA. Participants randomized to the placebo arm will receive oral placebo capsules prior to injection of saline solution (0.9%NaCI). Participants will be observed while taking the study product by site staff on approximately six occasions during the first two weeks of the oral run-in at Week 0 (Enrollment), at Week 2 (Oral Run-in Safety Visit), and on four separate DOT visits between Weeks 0 and 2. Cervicovaginal and rectal fluid will be collected for PK studies at a single follow-up visit. A subset of approximately 24 women at US sites will have vaginal tissue collection for PK studies at a single follow-up visit (Tissue Subset). Participants who present with Grade 2 or greater RELATED AEs during the oral-run in phase will not receive the injectable TMC278 LA. Participants who present with Grade 3 or 4 UNRELATED AEs will not proceed to the injectable phase unless approved by the Clinical Management Committee (CMC). Arm 1: Participants randomized to the active arm will receive rilpivirine 25 mg capsules once daily for four weeks to be taken orally with a meal. Participants will then receive IM injections of TMC278 LA, 1200 mg dose, at eight week intervals (at Weeks 4, 12, 20, 28, 36 and 44). On each dosing occasion 1200 mg of TMC278 LA will be delivered in two, 2 mL injections, one in each gluteus maximus muscle. All participants will receive a total of six doses (12 IM injections). Arm 2: Participants randomized to the placebo arm will receive placebo capsules once daily for four weeks to be taken orally with a meal. Participants will then receive IM injections of saline (0.9% NaCI) at eight week intervals (at Weeks 4, 12, 20, 28, 36 and 44). On each dosing occasion placebo will be delivered in two, 2 mL injections, one in each gluteus maximus muscle. All participants will receive a total of six doses (12 IM injections). Study sites: * Bronx Prevention Center CRS, USA * New Jersey Medical School CRS, USA * Emavundleni CRS, Cape Town, South Africa * Spilhaus CRS, Harare, Zimbabwe

Conditions

• Human Immunodeficiency Virus (HIV)

Interventions

Type	Name	Description
DRUG	Rilpivirine	Rilpivirine (TMC278), a non-nucleoside reverse transcriptase inhibitor (NNRTI) is a substituted diaryl-pyrimidine (DAPY) derivative with potent antiviral activity against HIV. It is approved by the US FDA for once daily oral administration and is effective as part of treatment for ARV-na'ive HIV-infected patients as rilpivirine 25 mg capsules. It is also co-formulated with TDF and FTC for use as a once- daily single fixed-dose combination (Complera™).
DRUG	Placebo	Participants randomized to the placebo arm will receive oral placebo capsules prior to injection of saline solution (0.9%NaCI). Participants will be observed while taking the study product by site staff on approximately six occasions during the first two weeks of the oral run-in at Week 0 (Enrollment), at Week 2 (Oral Run-in Safety Visit), and on four separate DOT visits between Weeks 0 and 2. Cervicovaginal and rectal fluid will be collected for PK studies at a single follow-up visit.

Timeline

• Start date: 2014-10-01
• Primary completion: 2015-04-13
• Completion: 2017-03-09
• First posted: 2014-06-17
• Last updated: 2018-08-27
• Results posted: 2018-07-26

Locations

4 sites across 3 countries: United States, South Africa, Zimbabwe