Safety and Acceptability of Cabotegravir in HIV Uninfected Women in KwaZulu-Natal, South Africa
- Registration Number
- NCT02462772
- 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.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Female
- Target Recruitment
- Not specified
- 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
- Total bilirubin < Grade 1
- Direct bilirubin < ULN
- Creatinine clearance ≥60 mL/min
- Hepatitis B surface antigen (HBsAg) negative
- Hepatitis C Ab negative
- In general good health, as assessed clinically
- 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
- history of non-sustained (3 consecutive ventricular ectopic beats on ECG at screening or entry) or sustained ventricular tachycardia
- History/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting surgery or percutaneous transluminal coronary angioplasty or any clinically significant cardiac disease
- Underlying skin disease or currently active skin disorder (e.g., infection, inflammation, dermatitis, eczema, psoriasis, urticaria). Mild cases of localized disease or other mild skin condition may not be exclusionary at the discretion of the Principal Investigator or designee.
- Has a tattoo or other dermatological condition overlying the buttock region which in the opinion of the Principal Investigator or designee, may interfere with interpretation of injection site reactions.
- History of acute or chronic liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy).
- Coagulopathy (primary or iatrogenic) which would contraindicate IM injection.
- Active or planned use of prohibited medications as described in the SSP manual (updated regularly from the Investigator's Brochure).
- Pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study.
- Known Hypersensitivity to egg, soya or peanut protein.
- Has any other condition that, based on the opinion of the Principal Investigator or designee, would preclude provision of informed consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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 Cabotegravir 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
- Primary Outcome Measures
Name Time Method Number of participants with adverse events 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 Outcome Measures
Name Time Method Acceptability of study injections and oral tablets 24 months Participant's opinions on the injections and tablets will be obtained through structured interviews.
Incidence of sexually transmitted infections 36 months Incidence of HIV, HSV-2, HPV, gonorrhoea, chlamydia and trichomonas infections in women
Impact on pregnancy 36 months The incidence of pregnancy and pregnancy outcomes in women assigned to cabotegravir and placebo will be compared
Resistance to antiretroviral drugs 36 months Viruses from HIV seroconverters will be sequenced and assessed for resistance mutations
Area under the plasma concentration versus time curve (AUC) of cabotegravir 36 months Cabotegravir concentrations will be measured throughout the study
HIV viral load in women who acquire HIV 36 months HIV viral load (copies/ml) will be measured and compared between the cabotegravir and placebo arms
Trial Locations
- Locations (2)
CAPRISA Vulindlela Research Clinic
🇿🇦Mafakatini, KwaZulu-Natal, South Africa
CAPRISA eThekwini Research Clinic
🇿🇦Durban, KwaZulu-Natal, South Africa