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

NCT02462772 | Withdrawn Phase 2 DMC

• 1 other identifier: CAPRISA 014
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Human Immunodeficiency Virus

Keywords

Cabotegravir; safety; long-acting injectable; HIV prevention; acceptability

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• Acceptability of study injections and oral tablets

  24 months

• Incidence of sexually transmitted infections

  36 months

• Area under the plasma concentration versus time curve (AUC) of cabotegravir

  36 months

• Impact on pregnancy

  36 months

• Resistance to antiretroviral drugs

  36 months

Other Outcomes (2)

• Pharmacogenomics of cabotegravir

  36 months

• Impact of contraception on area under the plasma concentration versus time curve (AUC) of cabotegravir

  36 months

Study Arms (2)

Cabotegravir

EXPERIMENTAL

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

Drug: cabotegravir

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

cabotegravir DRUG

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.

Also known as: GSK1265744

Cabotegravir

Placebo DRUG

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.

Also known as: Intralipid® 20%

Placebo

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Centre for the AIDS Programme of Research in South Africa: lead
• ViiV Healthcare: collaborator

Study Sites (2)

CAPRISA eThekwini Research Clinic

Durban, KwaZulu-Natal, 4001, South Africa

Location

CAPRISA Vulindlela Research Clinic

eMafakatini, KwaZulu-Natal, 3290, South Africa

Location

Related Publications (2)

• Radzio J, Spreen W, Yueh YL, Mitchell J, Jenkins L, Garcia-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.

  PMID: 25589631 BACKGROUND

• 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.

  PMID: 24100877 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

cabotegravir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Salim S Abdool Karim, MBCHB, PhD

  Centre for the AIDS Programme of Research in South Africa

  PRINCIPAL INVESTIGATOR

• Quarraisha Abdool Karim, PhD

  Centre for the AIDS Programme of Research in South Africa

  PRINCIPAL INVESTIGATOR

• Leila E Mansoor, PhD

  Centre for the AIDS Programme of Research in South Africa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: June 4, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: November 5, 2015

Record last verified: 2015-11

Locations

ZA (2)