Clinical Trials

MainTitle

Evaluating the Safety and Efficacy of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women

This study is currently recruiting participants. (see Contacts and Locations)

Verified November 2017 by National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)


Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03164564

First received: May 22, 2017
Last updated: November 29, 2017
Last Verified: November 2017
History of Changes
Purpose

Purpose

This study will evaluate the safety and efficacy of the long-acting injectable agent cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in HIV-uninfected women.

Condition Intervention Phase
HIV Infections

Drug : Oral CAB
Drug : Oral TDF/FTC
Drug : Placebo for oral CAB
Drug : Placebo for oral TDF/FTC
Drug : CAB LA
Drug : Placebo for CAB LA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Number of documented incident HIV infections in Steps 1 and 2 [ Time Frame: Measured through Week 81 ]
    HIV incidence rate will be calculated as the total number of participants with confirmed incident HIV infection during study follow-up of Step 1 and Step 2 divided by the person-years accumulated in each arm.
  • Number of Grade 3 or higher clinical and laboratory adverse events (AEs) [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    AEs will be summarized using MedDRA System Organ Class and preferred terms.
Secondary Outcome Measures:
  • Number of documented incident HIV infections in participants in subgroups broken down by baseline age [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.
  • Number of documented incident HIV infections in participants in subgroups broken down by baseline HSV-2 status [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.
  • Number of documented incident HIV infections in participants in subgroups broken down by baseline contraceptive use method [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.
  • Number of documented incident HIV infections in participants in subgroups broken down by baseline body mass index (BMI) less than/greater than or equal to 25 kg/m^2 [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    For each of the specified baseline factors, a Cox proportional hazards model will be fit with treatment arm, baseline factor and their interaction as covariates, stratified by site.
  • Plasma and dried blood spot (DBS) levels of CAB in participants randomized to CAB/CAB LA [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    Plasma and DBS samples for drug concentrations will be collected throughout the study from all participants, although PK testing may be limited to a subset of the samples.
  • Plasma levels of tenofovir/tenofovir diphosphate (TFV/TFV-DP) in participants randomized to TDF/FTC [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    Plasma samples for drug concentrations will be collected throughout the study from all participants, although PK testing may be limited to a subset of the samples.
  • Number of participants willing to use CAB LA and TDF/FTC [ Time Frame: Measured through participant's last study visit, up to 4.6 years after study entry, depending on when they enroll in the study ]
    Assessed through administration of brief behavioral surveys.

Estimated Enrollment: 3200
Study Start Date: November 1, 2017
Estimated Study Completion Date: May 2022
Estimated Primary Completion Date: May 2022 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Arm A: CAB + Placebo TDF/FTC + CAB LA
During Step 1, participants will receive daily oral CAB and oral TDF/FTC placebo for 5 weeks. In Step 2, participants will receive injections of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily oral TDF/FTC placebo beginning at Week 5. In Step 3, participants will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.
Drug: Oral CAB

CAB 30 mg tablet

Other Name: Cabotegravir
Drug: Oral TDF/FTC

TDF/FTC 300 mg/200 mg fixed dose combination tablet

Other Name:
  • Tenofovir disoproxil fumarate/emtricitabine
  • Truvada

Drug: Placebo for oral TDF/FTC

Placebo tablets

Drug: CAB LA

600 mg administered as one 3 mL (600 mg) intramuscular injection in the gluteal muscle

Other Name: Cabotegravir long-acting injectable
Active Comparator: Arm B: TDF/FTC + Placebo CAB + Placebo CAB LA
During Step 1, participants will receive daily TDF/FTC and oral CAB placebo for 5 weeks. In Step 2, participants will receive daily TDF/FTC and placebo for CAB LA injections at two times points 4 weeks apart and every 8 weeks thereafter beginning at Week 5. In Step 3, participants will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.
Drug: Oral TDF/FTC

TDF/FTC 300 mg/200 mg fixed dose combination tablet

Other Name:
  • Tenofovir disoproxil fumarate/emtricitabine
  • Truvada

Drug: Placebo for oral CAB

Placebo tablets

Drug: Placebo for CAB LA

Administered as one 3 mL intramuscular injection in the gluteal muscle

Detailed Description:

The purpose of this study is to evaluate the safety and efficacy of the long-acting injectable integrase inhibitor cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in a population of sexually active HIV-uninfected women at risk for HIV.
This study will take place in three steps. Participants will be randomly assigned to one of two arms:
Arm A:
Step 1: Participants will receive daily oral CAB and TDF/FTC placebo for 5 weeks.
Step 2: Participants will receive injections of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily TDF/FTC placebo beginning at Week 5.
Arm B:
Step 1: Participants will receive daily TDF/FTC and oral CAB placebo for 5 weeks.
Step 2: Participants will receive daily TDF/FTC and intramuscular (IM) placebo injections at two time points 4 weeks apart and every 8 weeks thereafter beginning at Week 5.
Step 2 will continue until the last enrolled participant reaches approximately 76 weeks on Step 2 (Week 81 for the last enrolled participant).
In Step 3, all participants (Arms A and B) will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.
At the end of Step 3, all participants will then transition to locally available HIV prevention services, including services for PrEP, if available.
Study visits will occur at Day 0 and at Weeks 2 and 4 during Step 1. During Step 2, participants will attend up to 24 visits, depending on when they enroll in the study. Study visits will occur every 12 weeks during Step 3. Study visits may include physical examinations; blood, urine, and vaginal swab collection; and risk reduction and adherence counseling.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 45 Years  
Sexes Eligible for Study: Female  
Accepts Healthy Volunteers: Yes  

Criteria

Inclusion Criteria:

  • Born female
  • 18-45 years at the time of screening
  • Willing and able to provide informed consent
  • Willing and able to undergo all required study procedures
  • Non-reactive HIV test results at Screening and Enrollment. Note: HIV-uninfected, based on HIV test results obtained at Screening and just prior to randomization at the Enrollment visit. All HIV test results from the Screening visit must be obtained and must all be negative/non-reactive. This includes testing for acute HIV infection, which must be performed within 14 days of Enrollment. In addition, at least one HIV test result using blood drawn at the Enrollment visit must be obtained prior to randomization into the study and must be negative/non-reactive. Individuals who have one or more reactive or positive HIV test result(s) will not be enrolled, even if subsequent confirmatory testing indicates that they are not HIV-infected (see SSP Manual).
  • Sexually active (i.e., vaginal intercourse on a minimum of two separate days in the 30 days prior to Screening)
  • Score of greater than or equal to 2 using a modified VOICE risk score
  • No plans to re-locate or travel away from the site for greater than or equal to 8 consecutive weeks during study participation
  • Creatinine clearance of greater than or equal to 60 mL/min (using Cockcroft-Gault equation)
  • Hepatitis B virus (HBV) surface antigen (HBsAg) negative and accepts vaccination
  • Alanine aminotransferase (ALT) less than 2 x upper limit of normal (ULN) and total bilirubin (Tbili) less than or equal to 2.5 x ULN
  • HCV antibody negative
  • If of reproductive potential (defined as pre-menopausal women who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative beta human chorionic gonadotropin (βHCG) pregnancy test (sensitivity of less than or equal to 25 mIU/mL) performed (and results known) on the same day as and before initiating the protocol-specified study product(s) at Enrollment.
  • If of reproductive potential, women must agree to use a reliable form of contraception, during the trial and for 52 weeks after stopping the long acting injectable, or 30 days after stopping oral study product, from the list below:
    • Intrauterine device (IUD) or intrauterine system (IUS) that meets less than 1% failure rate as stated in the product label
    • Hormone-based contraceptive that meets less than 1% failure rate when used consistently and correctly as stated in the product label
  • No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
  • No alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records)


Exclusion Criteria:
  • One or more reactive HIV test results at Screening or Enrollment, even if HIV infection is not confirmed
  • Pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study
  • Co-enrollment in any other HIV interventional research study (provided by self-report or other available documentation)
  • Current or past enrollment in an HIV vaccine trial
  • Current or chronic history of 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)
  • History of seizure disorder, per self-report
  • Clinically significant cardiovascular disease, as defined by history/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease
  • Inflammatory skin conditions that compromise the safety of IM injections, per the discretion of the Investigator of Record (IoR). Mild skin conditions may not be exclusionary at the discretion of the IoR or designee
  • Has a tattoo or other dermatological condition overlying the buttock region which in the opinion of the IoR or designee may interfere with interpretation of injection site reactions (ISRs)
  • Coagulopathy (primary or iatrogenic) which would contraindicate IM injection
  • Active or planned use of prohibited medications as described in the Investigator Brochure (IB) or listed in the Study Specific Procedures Manual (SSP) (provided by self-report, or obtained from medical history or medical records)
  • Known or suspected allergy to study product components (active or placebo), including
egg or soy products (egg and soy products are contained in Intralipid)

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: NCT03164564

Locations

Botswana
Gaborone CRS Recruiting
Gaborone, South-East District, Botswana
Contact: Tebogo J. Kakhu    267-3931353    tkakhu@bhp.org.bw
South Africa
Soweto HPTN CRS Recruiting
Johannesburg, Gauteng, South Africa, 1862
Contact: Dimakatso Koenane    27-11-9899700    koenaned@phru.co.za
Ward 21 CRS Recruiting
Johannesburg, Gauteng, South Africa, 2001
Contact: Sarah Cohen    27-11-3585300    scohen@wrhi.ac.za

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Sinead Delany-Moretlwe, MBBCh, PhD, DTM&H Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
Study Chair: Mina Hosseinipour, MD, MPH University of North Carolina (UNC) Project-Malawi, Tidziwe Centre
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT03164564   History of Changes  
Other Study ID Numbers: HPTN 084  
  38070  
Study First Received: May 22, 2017  
Last Updated: November 29, 2017  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
HIV Infections
Emtricitabine
Tenofovir

ClinicalTrials.gov processed this data on December 08, 2017
This information is provided by ClinicalTrials.gov.