Safety and Acceptability of Cabotegravir in HIV Uninfected Women in KwaZulu-Natal, South Africa

Human Immunodeficiency Virus Clinical Trial

— CAPRISA014  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02462772
• Other study ID #: CAPRISA 014
• Status: Withdrawn
• Phase: Phase 2
• First received: May 27, 2015
• Last updated: November 4, 2015
• Start date: October 2015
• Est. completion date: September 2018

Study information

• Verified date: November 2015
• Source: Centre for the AIDS Programme of Research in South Africa
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2018
• Est. primary completion date: September 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 30 Years

Eligibility

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

• 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

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

• 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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes

Intervention

Drug:
• cabotegravir
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
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.

Locations

Country	Name	City	State
South Africa	CAPRISA eThekwini Research Clinic	Durban	KwaZulu-Natal
South Africa	CAPRISA Vulindlela Research Clinic	Mafakatini	KwaZulu-Natal

Sponsors (2)

Lead Sponsor	Collaborator
Centre for the AIDS Programme of Research in South Africa	ViiV Healthcare

Country where clinical trial is conducted

South Africa, 

References & Publications (2)

Radzio J, Spreen W, Yueh YL, Mitchell J, Jenkins L, García-Lerma JG, Heneine W. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge. Sci Transl Med. 2015 Jan 14;7(270):270ra5. doi: 10.1126/scitranslmed.3010297. — View Citation

Spreen WR, Margolis DA, Pottage JC Jr. Long-acting injectable antiretrovirals for HIV treatment and prevention. Curr Opin HIV AIDS. 2013 Nov;8(6):565-71. doi: 10.1097/COH.0000000000000002. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacogenomics of cabotegravir	The impact of genetic polymorphisms on response to cabotagravir LA will be assessed	36 months	No
Other	Impact of contraception on area under the plasma concentration versus time curve (AUC) of cabotegravir	Cabotegravir concentrations in women on DMPA will be compared to women on other forms of contraception	36 months	Yes
Primary	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.	36 months	Yes
Secondary	Acceptability of study injections and oral tablets	Participant's opinions on the injections and tablets will be obtained through structured interviews.	24 months	No
Secondary	Incidence of sexually transmitted infections	Incidence of HIV, HSV-2, HPV, gonorrhoea, chlamydia and trichomonas infections in women	36 months	No
Secondary	Area under the plasma concentration versus time curve (AUC) of cabotegravir	Cabotegravir concentrations will be measured throughout the study	36 months	No
Secondary	Impact on pregnancy	The incidence of pregnancy and pregnancy outcomes in women assigned to cabotegravir and placebo will be compared	36 months	Yes
Secondary	Resistance to antiretroviral drugs	Viruses from HIV seroconverters will be sequenced and assessed for resistance mutations	36 months	Yes
Secondary	HIV viral load in women who acquire HIV	HIV viral load (copies/ml) will be measured and compared between the cabotegravir and placebo arms	36 months	No