A Phase IIa Safety, Tolerability and Acceptability Study of an Investigational Injectable HIV Integrase Inhibitor, GSK1265744, for PrEP in HIV Uninfected Men and Women
What is HPTN 077?
HPTN 077 is a study being done to learn more about the safety and acceptability of a drug called cabotegravir (sometimes also referred to as GSK 1265744) when taken orally and injected by HIV uninfected men and women. The study product was provided by GlaxoSmithKline on behalf of ViiV Healthcare.
Who participated in the study?
HPTN 077 enrolled approximately 200 HIV-uninfected men and women in 8 cities: Rio de Janeiro, Brazil; Lilongwe, Malawi; Vulindlela and Soweto, South Africa; Chapel Hill, North Carolina; Los Angeles and San Francisco, California; and Washington, District of Columbia. To enroll in the study, participants had to be deemed low risk for HIV infection, at least 18 years old, and able to provide written informed consent. Enrollment in to the study is completed and follow-up is ongoing.
Why is HPTN 077 important?
HPTN 077 is an important next step in helping to determine if future research should be done to see if injectable cabotegravir can be used for pre-exposure prophylaxis (PrEP) in people at greater risk of acquiring HIV.
What happened during the study?
Study participants were randomly placed in one of two groups. One group was given pills and injections that had the cabotegravir in it. Approximately seventy-five percent of participants were in this group. The other group was given pills and injections that did not have cabotegravir in it. This is called a placebo. The placebo forms of the drug typically look like the active or “real” drug, but they do not have the drug or any other medicine in them. Approximately twenty-five percent of participants were in this group. The researchers and participants did not know who is getting active drug.
Participants were told that one of the best things they can do to protect themselves from getting HIV and other sexually transmitted infections (like gonorrhea, syphilis or chlamydia) was to use a condom every time they have sex.
Participants had approximately 19 – 22 study visits over the course of the entire study, which lasted for about two years. At these visits the participants received a physical exam, including checking to see the health of their heart, liver, bones and kidneys, and discussed any concerns or side effects that may be related to the study drugs. All participants received HIV testing and prevention counseling, as well as condoms at each study visit.
What were the results of the study?
HPTN 077 showed that cabotegravir:
- It is safe and well tolerated
- The dosing being used in HPTN 083 and HPTN 084 is supported by PK data from HPTN 077
- Cabotegravir is not associated with weight gain in HIV negative individuals
- Cabotegravir does not seem to have clinically significant interactions with hormonal contraception.
- The half-life is more prolonged in females compared to males, and longer for those with higher Body Mass Index
Photos provided by ViiV Healthcare
HPTN 077 Version 3.0
- HPTN 077 Protocol V3.0 - 13 Oct. 2015
- Version 3.0: Letter of Amendment #3 - 7 Nov 2016
- Version 3.0: Letter of Amendment #2 - 28 July 2016
- Version 3.0: Letter of Amendment #1 - 6 July 2016
HPTN 077 Version 2.0
- HPTN 077 Protocol V2.0 - 18 Nov 2014
- Version 2.0: Letter of Amendment #1 30 Mar 2015
- Version 2.0: Letter of Amendment #2 6 July 2015
- Version 2.0: Clarification Memo #1 - 4 Dec 2014
- Version 2.0: Clarification Memo #2 – 9 Feb 2015
HPTN 077 Version 1.0
- HPTN 077 Protocol V1.0 - 1 May 2014
- Version 1.0: Letter of Amendment #1 - 14 July 2014
- Version 1.0: Clarification Memo #1 - 5 Aug 2014
More Study Documents
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To evaluate the safety, tolerability, pharmacokinetics and acceptability of the injectable agent, GSK1265744 long-acting injectable (744LA), in healthy, HIV-uninfected men and women.
Multi-site, double-blind, two-arm, randomized, placebo-controlled trial of the safety, tolerability, and acceptability of 744LA.
HIV-uninfected men and women at low to minimal risk for acquiring HIV infection, ages 18 to 65.
Approximately 194 men and women, randomized 3:1, with approximately 145 in the active drug arm, and approximately 49 in the placebo arm. It is anticipated that approximately 60% of the enrolled participants will be women. Two cohorts will be enrolled (Cohort 1 and Cohort 2). Cohort 1 will include approximately 106 participants (approximately 40 men and 66 women), and Cohort 2 will include approximately 88 participants (approximately 35 men and 53 women).
Approximately 3 and a half years. Accrual will require approximately 16 to 24 weeks (4 – 6 months) for each cohort. Participants in both cohorts will receive oral tablets for 4 weeks, followed by a 1 week wash out period. Cohort 1 will then receive intra-muscular (IM) injections at 3 time points over 24 weeks (6 months); Cohort 2 will receive IM injections at 5 time points over 28 weeks (7 months). Participants in the active study product arm will be followed for 52 weeks (12 months) after their last injection or 76 weeks after their last injection, depending on whether they completed the study before the follow-up was extended to 76 weeks or if they did not agree to be followed for 76 weeks. Participants in the placebo arm will be followed until 52 weeks after their last injection or until the last participant in the active study product arm of Cohort 2 completes their Week 41 visit, whichever comes first, after which the cohorts will be unblinded to assess the primary endpoint. When all procedures related to unblinding are completed, participants in the placebo arms of both cohorts will no longer be followed.
Participants will be randomized to receive daily oral GSK1265744 (30 mg tablets) or daily oral placebo for 4 weeks, followed by a one-week washout, to assess safety and tolerability before they receive injections. After safety and tolerability assessments from the oral phase have been completed (if no concerns are identified), participants will enter the injection phase of the study and will receive two intra-muscular (IM) gluteal injections of 744LA (800 mg, administered as two 400 mg injections) or placebo (matching vehicle control) at three study visits performed at 12-week intervals.
Evaluate the safety and tolerability of the injectable agent GSK1265744 long acting (744LA) injectable (800 mg dose administered at three time points at 12 week intervals), through Week 41 in HIV-uninfected men and women. Evaluate the safety and tolerability of the injectable agent GSK1265744 long acting (744LA) injectable (600 mg dose administered at two time points at 4 week intervals, followed by three time points at 8 week intervals), through Week 41 in HIV-uninfected men and women.
Evaluate the safety and tolerability of GSK1265744 (daily oral 744 + 744LA) for 52 weeks of follow-up after final injection (each cohort will be analyzed separately); Evaluate the safety and tolerability of oral 744 from Week 0 to Week 5; Evaluate the pharmacokinetics of 744LA administered at three time points as 800 mg IM every 12 weeks for 52 weeks of follow-up after final injection; Evaluate the pharmacokinetics of 744LA administered at five time points as 600 mg IM at two time points every 4 weeks followed by three time points every 8 weeks for 52 weeks of follow-up after final injection; Evaluate differential pharmacokinetics of 744LA in participants by age, gender, race, ethnicity, weight, body mass index (BMI), and smoking status; Evaluate the acceptability of 744LA injections; Evaluate the effect of 744LA on sexual risk behavior by change from enrollment over time during the study period; Evaluate HIV incidence and antiretroviral drug resistance, in participants who acquire HIV infection during the study; Evaluate the safety, tolerability and pharmacokinetics of 744LA in the subset of women who use a hormone-based contraceptive.