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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Cabotegravir 30 mg tablets are formulated as white to almost white oval-shaped coated tablets for oral administration. The cabotegravir LA is formulated as a sterile white to slightly coloured suspension containing 400mg/2mL of cabotegravir LA for administration by IM injection.
Placebo tablets for cabotegravir are formulated as white to almost white oval-shaped coated tablets to visually match the active cabotegravir tablets. Placebo for cabotegravir injectable suspension is Intralipid® 20%. Intralipid® is a fat emulsion with no pharmacological action. It is a white, milky emulsion, consisting of purified soyabean oil, purified egg phospholipids and anhydrous glycerol. Intralipid® 20% is supplied in infusion bags.
CAPRISA eThekwini Research Clinic
Durban, KwaZulu-Natal, South Africa
CAPRISA Vulindlela Research Clinic
eMafakatini, KwaZulu-Natal, South Africa
Number of participants with adverse events
The incidence of increase in graded AEs and in particular liver enzymes (AST/ALT) at the level of Grade 3 or higher.
Time frame: 36 months
Acceptability of study injections and oral tablets
Participant's opinions on the injections and tablets will be obtained through structured interviews.
Time frame: 24 months
Incidence of sexually transmitted infections
Incidence of HIV, HSV-2, HPV, gonorrhoea, chlamydia and trichomonas infections in women
Time frame: 36 months
Area under the plasma concentration versus time curve (AUC) of cabotegravir
Cabotegravir concentrations will be measured throughout the study
Time frame: 36 months
Impact on pregnancy
The incidence of pregnancy and pregnancy outcomes in women assigned to cabotegravir and placebo will be compared
Time frame: 36 months
Resistance to antiretroviral drugs
Viruses from HIV seroconverters will be sequenced and assessed for resistance mutations
Time frame: 36 months
HIV viral load in women who acquire HIV
HIV viral load (copies/ml) will be measured and compared between the cabotegravir and placebo arms
Time frame: 36 months
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