Phase II Safety and Acceptability of an Investigational Injectable Product, TMC278LA, for Pre-Exposure Prophylaxis
Condition: Human Immunodeficiency Virus (HIV)
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Phase 2

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
    

Intervention name(s): Rilpivirine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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™).; 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.
Intervention MeSH terms: Rilpivirine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: HIV Pre-exposure Prophylaxis;; long-acting injectable;; HIV PrEP;; biomedical HIV prevention research