Clinical Trials

MainTitle

Safety and Acceptability of Cabotegravir in HIV Uninfected Women in KwaZulu-Natal, South Africa (CAPRISA014)

This study has been withdrawn
Sponsor
Centre for the AIDS Programme of Research in South Africa

Collaborator
ViiV Healthcare

Information provided by (Responsible Party)
Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa

ClinicalTrials.gov Identifier
NCT02462772

First received: May 27, 2015
Last updated: November 4, 2015
Last Verified: November 2015
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
Human Immunodeficiency Virus

Drug : cabotegravir
Drug : Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Further study details as provided by Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa:

Primary Outcome Measures

  • 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 Outcome Measures:
  • Acceptability of study injections and oral tablets [ Time Frame: 24 months ]
    Participant's opinions on the injections and tablets will be obtained through structured interviews.
  • Incidence of sexually transmitted infections [ Time Frame: 36 months ]
    Incidence of HIV, HSV-2, HPV, gonorrhoea, chlamydia and trichomonas infections in women
  • Area under the plasma concentration versus time curve (AUC) of cabotegravir [ Time Frame: 36 months ]
    Cabotegravir concentrations will be measured throughout the study
  • Impact on pregnancy [ Time Frame: 36 months ]
    The incidence of pregnancy and pregnancy outcomes in women assigned to cabotegravir and placebo will be compared
  • Resistance to antiretroviral drugs [ Time Frame: 36 months ]
    Viruses from HIV seroconverters will be sequenced and assessed for resistance mutations
  • HIV viral load in women who acquire HIV [ Time Frame: 36 months ]
    HIV viral load (copies/ml) will be measured and compared between the cabotegravir and placebo arms
Other Outcome Measures:
  • Pharmacogenomics of cabotegravir [ Time Frame: 36 months ]
    The impact of genetic polymorphisms on response to cabotagravir LA will be assessed
  • Impact of contraception on area under the plasma concentration versus time curve (AUC) of cabotegravir [ Time Frame: 36 months ]
    Cabotegravir concentrations in women on DMPA will be compared to women on other forms of contraception

Enrollment: 0
Study Start Date: October 2015
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 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
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.

Other Name: GSK1265744
Placebo Comparator: 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
Drug: 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.

Other Name: Intralipid® 20%

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 30 Years  
Sexes Eligible for Study: Female  
Accepts Healthy Volunteers: Yes  

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
  • 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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02462772

Locations

South Africa
CAPRISA eThekwini Research Clinic
Durban, KwaZulu-Natal, South Africa, 4001
CAPRISA Vulindlela Research Clinic
Mafakatini, KwaZulu-Natal, South Africa, 3290

Sponsors and Collaborators

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

Investigators

Principal Investigator: 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
More Information

More Information


Responsible Party: Dr Salim S Abdool Karim, Principal Investigator, Centre for the AIDS Programme of Research in South Africa  
ClinicalTrials.gov Identifier: NCT02462772   History of Changes  
Other Study ID Numbers: CAPRISA 014  
Study First Received: May 27, 2015  
Last Updated: November 4, 2015  

Keywords provided by Dr Salim S Abdool Karim, Centre for the AIDS Programme of Research in South Africa:

Cabotegravir
safety
long-acting injectable
HIV prevention
acceptability

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Soybean oil, phospholipid emulsion
HIV Integrase Inhibitors

ClinicalTrials.gov processed this data on December 15, 2017
This information is provided by ClinicalTrials.gov.