Phase II Trial to Assess the Safety and Acceptability of the Long-acting Injectable HIV Integrase Inhibitor, Cabotegravir (GSK1265744), in HIV Uninfected Women in KwaZulu-Natal, South Africa
Overview
- Phase
- Phase 2
- Intervention
- cabotegravir
- Conditions
- Human Immunodeficiency Virus
- Sponsor
- Centre for the AIDS Programme of Research in South Africa
- Locations
- 2
- Primary Endpoint
- Number of participants with adverse events
- Status
- Withdrawn
- Last Updated
- 10 years ago
Overview
Brief Summary
The CAPRISA 014 trial aims to assess the safety and acceptability of the long-acting (LA) injectable antiretroviral agent, cabotegravir LA (GSK1265744), in HIV uninfected women in KwaZulu-Natal, South Africa.
Detailed Description
The CAPRISA 014 trial is designed to establish the safety and acceptability of cabotegravir LA in sexually active, at-risk HIV-uninfected women. A total of 632 HIV uninfected women (18 to 30 years) from two sites in KwaZulu-Natal, South Africa will be enrolled. The trial will be approximately 24 months, with an additional 12 months post-trial safety observation. The study is divided into three periods: Period 1 - Clinical trial oral lead-in (up to 34 days) - Consenting participants will be randomized to receive daily oral cabotegravir (30mg tablets) or daily oral placebo for approximately 30 days, to assess safety and tolerability prior to exposure to the LA injectable formulation. Period 2 - Clinical trial follow-up with injectable (approximately 48-96 weeks) - Participants who have successfully completed Period 1 will receive intra-muscular (IM) gluteal injections of cabotegravir LA (800 mg, administered as two 400 mg injections) or placebo every 12 weeks. The end of Period 2 marks the completion of clinical trial follow-up. Period 3 - Post-trial safety follow-up off-product (approximately 12 months) - During this post-trial safety observation period, participants will be followed up (off product) for approximately 12 months after completion of period 2.
Investigators
Dr Salim S Abdool Karim
Principal Investigator
Centre for the AIDS Programme of Research in South Africa
Eligibility Criteria
Inclusion Criteria
- •Able and willing to provide written informed consent to be screened for, and to enrol in, the study.
- •Able and willing to provide adequate locator information for study retention purposes.
- •Sexually active, defined as having had vaginal intercourse at least once in the past 30 days prior to screening.
- •HIV negative on testing performed by study staff
- •Have a negative pregnancy test performed by study staff
- •Agree to use a non-barrier form of contraceptive
- •Agree to adhere to study visits and procedures.
- •Haemoglobin \> 11 g/dL,
- •ALT \< ULN
- •AST \< ULN
Exclusion Criteria
- •Past or current participation in any other HIV interventional research study or other concurrent studies which may interfere with this study.
- •Clinically significant cardiovascular disease, including:
- •ECG with:
- •heart rate \<50 or \>100 beats per minute (one repeat ECG is allowed during screening; can be performed on the same day)
- •QRS duration \>120 msec
- •QTc interval (B or F) \> 450 msec
- •evidence of previous myocardial infarction (pathologic Q waves, S-T segment changes (except early repolarization)
- •any conduction abnormality (including but not specific to left or right complete bundle branch block, Atrioventricular block \[2nd degree (type II) or higher\], Wolf Parkinson White syndrome)
- •sinus pauses \> 3 seconds
- •any significant arrhythmia which, in the opinion of the Principal Investigator or designee, will interfere with the safety for the individual participant
Arms & Interventions
Cabotegravir
Women randomised to the cabotegravir arm will receive daily oral cabotegravir (30 mg tablets) for approximately 30 days and thereafter will receive intra-muscular gluteal injections of cabotegravir LA (800 mg, administered as two 400 mg injections) every 12 weeks
Intervention: cabotegravir
Placebo
Women randomised to the placebo arm will receive daily oral tablets (30 mg tablets) for approximately 30 days and thereafter will receive intra-muscular gluteal injections of Intralipid® 20% every 12 weeks
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants with adverse events
Time Frame: 36 months
The incidence of increase in graded AEs and in particular liver enzymes (AST/ALT) at the level of Grade 3 or higher.
Secondary Outcomes
- Acceptability of study injections and oral tablets(24 months)
- Incidence of sexually transmitted infections(36 months)
- Impact on pregnancy(36 months)
- Resistance to antiretroviral drugs(36 months)
- Area under the plasma concentration versus time curve (AUC) of cabotegravir(36 months)
- HIV viral load in women who acquire HIV(36 months)