HPTN 084 is a Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women.

The main purpose of this study is to find out if a new drug called cabotegravir (CAB), an antiretroviral used as PrEP, will protect women from getting HIV. CAB comes in the form of a pill and also as an injection (shot). CAB has shown to be effective in treating HIV, but researchers do not yet know if CAB protects people from getting HIV. Neither CAB pills nor CAB injections are approved by the US FDA for the treatment and prevention of HIV infection. CAB pills and CAB injections are considered investigational drugs. In this study, we want to find out whether the injection form of CAB, which is active for a longer time in the body than the pill form, can protect people from HIV. Based on studies in MSM and heterosexual couples, TDF/FTC was approved as an agent for PrEP. Therefore, it is considered to be the ethically appropriate active comparator for CAB LA, an experimental PrEP agent.

This is a Phase 3, randomized, multi-site, two-arm, double-blind study of CAB LA compared to daily oral TDF/FTC for HIV prevention.  Approximately 3,200 participants will be enrolled and randomized 1:1 to Arm A (CAB LA and placebo TDF/FTC) and Arm B (TDF/FTC and CAB LA placebo) through the three Steps listed below.  When the study reaches the required number of incident HIV endpoints (111), all participants will begin open-label daily oral TDF/FTC for approximately 48 weeks (to “cover the tail”), starting no later than 8 weeks after the last injection. 

Step 1, Oral Run-in Phase:

Arm A – Daily oral CAB and oral TDF/FTC placebo for five weeks plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

Arm B – Daily TDF/FTC and oral CAB placebo for five weeks plus an HIV prevention

package including behavioral risk reduction and adherence counseling, provision of

condoms.

Any participant who becomes HIV-infected during Step 1 will permanently discontinue study product, will be terminated from the study, and referred for HIV-related care. 

Step 2, Injection Phase:

Arm A – Injections of CAB LA at two time points four weeks apart and every eight weeks thereafter and daily oral TDF/FTC placebo beginning at Week 5 plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.  Injections will consist of 600 mg of CAB LA administered as one 3 mL IM injection. 
 

Arm B – Daily TDF/FTC and IM placebo (matching vehicle, identical volume as active injectable product in Arm A) beginning at Week 5 plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

This Step will continue until the required number of incident HIV endpoints (111) is reached, estimated to be when the last enrolled participant reaches approximately 76 weeks on Step 2 (Week 81 for the last enrolled participant).

Participants who permanently discontinue receiving injections before their study participation ends for any reason other than HIV infection will begin open-label TDF/FTC to cover the tail phase.  These participants will continue to be followed according to their Step 2 schedule and upon its completion move into Step 3.

Any participant who becomes HIV-infected during Step 2 will permanently discontinue study product, be referred for care, and will be followed at quarterly intervals for approximately 48 weeks.     

Step 3, Follow-up Phase: 

Arms A and B – Open-label daily TDF/FTC up to 48 weeks (to “cover the tail”), starting no later than 8 weeks after the last injection plus an HIV prevention package including behavioral risk reduction and adherence counseling, and provision of condoms. 

All participants will be transitioned to locally-available HIV prevention services including services for PrEP, if available. when participation in Step 3 ends. 

Any participant who becomes HIV-infected during Step 3 will permanently discontinue product, continue to be followed for the duration of Step 3 visits (with possible additional assessments and follow-up determined by the CMC), and referred for HIV-related care. 

All participants will receive HIV testing with pre- and post-test counseling, risk-reduction counseling, and be offered condoms.  All participants will be followed according to the Schedule of Evaluations (SOE) provided in Appendices I a-c, and in the event of possible HIV infection, according to Appendix II. 

Injectable Contraceptive Sub-study:

Up to 100 evaluable participants will be invited to enroll a sub-study after screening to evaluate the effect of CAB LA on the injectable contraceptive drugs: DMPA and NET-EN. Participants who are currently on these drugs or are willing to use these drugs as contraceptive methods qualify for the enrollment. These participants will go through all of the study procedures as all others participants, and extra PK samples will be collected prior to when Step 1 starts and also during the Step 2. PK sampling time collections may vary depending on the injectable contraceptive schedule.