ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03164564
Recruitment Status : Recruiting
First Posted : May 23, 2017
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
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 or disease Intervention/treatment 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

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; risk reduction, adherence counseling, and contraception counseling.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3200 participants
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
Actual Study Start Date : November 7, 2017
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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 Names:
  • 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 Names:
  • 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




Primary Outcome Measures :
  1. 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.

  2. 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 :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
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 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.
  • Have documented evidence of surgical sterilization, OR documented evidence of no uterus (e.g., hysterectomy), OR must agree to use a reliable form of long acting 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 (implants or injectables only; this excludes combined oral contraception)
  • 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:

  • If potentially able to conceive, unwilling to adhere to long acting contraception (IUD/IUS, injection, or implant) with a less than 1% failure rate when used consistently and correctly as stated in the product package insert/ manufacturer's guidelines
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03164564


Locations
Botswana
Gaborone CRS Recruiting
Gaborone, South-East District, Botswana
Contact: Tebogo J. Kakhu    267-3931353    tkakhu@bhp.org.bw   
Kenya
Kisumu Crs Recruiting
Kisumu, Nyanza, Kenya, 40100
Contact: Rose Abwunza, B.A., M.A.    254-721410654    rabwunza@kemricdc.org   
Malawi
Malawi CRS Recruiting
Lilongwe, Central, Malawi
Contact: Whitney Ewing    265-993 67 50 24    wewing@email.unc.edu   
Blantyre CRS Recruiting
Blantyre, Malawi
Contact: Bonus Makanani, M.B.B.S., B.Sc.    265-1875129    bmakanani@jhu.medcol.mw   
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: Admire Chikandiwa    27-11-3585856    achikandiwa@wrhi.ac.za   
Botha's Hill CRS Recruiting
Durban, Kwa Zulu Natal, South Africa, 3660
Contact: Ncamsile Sibisi    27-031-7771585    Ncamsile.Sibisi@mrc.ac.za   
Isipingo CRS Recruiting
Isipingo Rail, Kwa Zulu Natal, South Africa, 4110
Contact: Girisha Kistnasami, B.Sc., D.P.M.    27-31-9027494    girisha.kistnasami@mrc.ac.za   
Verulam CRS Recruiting
Verulam, Kwa Zulu Natal, South Africa, 4340
Contact: Ziningi Jaya    27-32-5334145    Ziningi.Dwayisa@mrc.ac.za   
Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS Recruiting
Cape Town, Western Cape Province, South Africa, 7505
Contact: Frieda A. Verheye-Dua    27-21-9389772    Frieda@sun.ac.za   
Emavundleni CRS Recruiting
Cape Town, Western Cape, South Africa, 7750
Contact: Elaine Sebastian    27-21-6505848    elaine.sebastian@hiv-research.org.za   
Uganda
UVRI-IAVI HIV Vaccine Program LTD. CRS Recruiting
Entebbe, Uganda
Contact: Barbarah Kawoozo    256-782-700404    bkawoozo@iavi.or.ug   
Baylor-Uganda CRS Recruiting
Kampala, Uganda
Contact: Violet Korutaro    256-417-119200    vkorutaro@baylor-uganda.org   
MU-JHU Research Collaboration (MUJHU CARE LTD) CRS Recruiting
Kampala, Uganda
Contact: Carolyne P. Onyango, MB ChB, M.S.    256-414-541044    carolonyango@mujhu.org   
Zimbabwe
Zengeza CRS Recruiting
Chitungwiza, Mashonaland East, Zimbabwe
Contact: Petina Musara, B.Sc.    263-4-2915421    pmusara@uzchs-ctrc.org   
Seke South CRS Recruiting
Chitungwiza, Zimbabwe
Contact: Thandiwe H. Chirenda, RGN, MPH    263-4-704890    tchirenda@uzchs-ctu.org   
St Mary's CRS Recruiting
Chitungwiza, Zimbabwe
Contact: Emmie Marote, R.N., B.A.    263-772-268519    emarote@uzchs-ctrc.org   
Parirenyatwa CRS Recruiting
Harare, Zimbabwe
Contact: Rachel Mahachi, M.Sc., R.N.    263-4-701356    rmahachi@uzcrc.co.zw   
Spilhaus CRS Recruiting
Harare, Zimbabwe
Contact: Eunice Tahuringana    263-772-882704    etahuringana@uzchs-ctrc.org   
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

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03164564     History of Changes
Other Study ID Numbers: HPTN 084
38070 ( Registry Identifier: DAIDS-ES Registry Number )
First Posted: May 23, 2017    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018

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

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Emtricitabine
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents