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Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), For Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women Who Have Sex With Men

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ClinicalTrials.gov Identifier: NCT02720094
Recruitment Status : Recruiting
First Posted : March 25, 2016
Last Update Posted : July 19, 2019
Sponsor:
Collaborators:
ViiV Healthcare
Gilead Sciences
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE March 21, 2016
First Posted Date  ICMJE March 25, 2016
Last Update Posted Date July 19, 2019
Study Start Date  ICMJE December 2016
Estimated Primary Completion Date March 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2016)
  • Number of documented incident HIV infections in Steps 1 and 2 [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
  • Number of Grade 2 or higher clinical and laboratory adverse events [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02720094 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2016)
  • Number of documented incident HIV infections in Step 2 [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
  • Number of documented incident HIV infections in Steps 1, 2, and 3 [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
  • Number of documented incident HIV infections in Step 3 [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
  • Number of documented incident HIV infections in Step 2 and 3 [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
  • Changes from baseline in creatinine and creatinine clearance levels [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
  • Number of Grade 3 or 4 liver-related adverse events (AEs) [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
    (laboratory assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBili, creatine phosphokinase (CPK), or clinical assessment of jaundice/icterus).
  • Changes in Z-score from baseline and DXA criteria for osteopenia and osteoporosis [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
  • Incidence of resistance mutations to study products (including but not limited to K65R, M184V/I, Q148R) among seroconverters [ Time Frame: Measured through participant's last study visit, up to 4.5 years after study entry ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), For Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women Who Have Sex With Men
Official Title  ICMJE A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), For Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women Who Have Sex With Men
Brief Summary This study will evaluate the safety and efficacy of the injectable drug cabotegravir (CAB LA), for pre-exposure prophylaxis (PrEP) in HIV-uninfected cisgender men and transgender women who have sex with men (MSM and TGW).
Detailed Description

The purpose of this study is to evaluate the safety and efficacy of the injectable drug cabotegravir (CAB LA), for pre-exposure prophylaxis (PrEP) in HIV-uninfected cisgender men and transgender women who have sex with men (MSM and TGW).

This study will enroll HIV-uninfected MSM and TGW at risk for acquiring HIV infection. Participants will remain in the study between 1.5 years to 4.5 years, depending on when they enroll in the study.

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 tablets and daily oral TDF/FTC placebo tablets for 5 weeks.

Step 2: Participants will receive an intramuscular (IM) injection of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily oral TDF/FTC placebo tablets.

Arm B:

Step 1: Participants will receive daily oral TDF/FTC tablets and daily oral CAB placebo tablets for 5 weeks.

Step 2: Participants will receive daily oral TDF/FTC tablets and an IM injection of placebo at two time points 4 weeks apart and every 8 weeks thereafter.

In Step 3, all participants (Arms A and B) will receive daily oral TDF/FTC tablets no later than 8 weeks after the last injection, for up to 48 weeks.

Participants will attend up to 57 study visits throughout the study. Visits may include physical examinations, blood collection, urine collection, an electrocardiogram (ECG), and rectal swab collection. Some participants may have a bone mineral density-energy x-ray absorptimetry (DXA) scan at select visits.

All participants will be transitioned to locally available HIV prevention services, including services for PrEP, if available, at the end of their participation in the study.

HPTN 083-02 is a qualitative sub-study of participants enrolled in HPTN 083. The purpose of this study is to explore potential barriers, facilitators, and potentially modifiable issues related to adherence to clinic visits in the context of injectable PrEP; to learn about preferences and decision making regarding the use of oral versus injectable PrEP, or other biomedical prevention products; and to gather explanatory qualitative data regarding participants' experiences in HPTN 083 to better interpret study results and guide next prevention strategies. Participants in this sub-study will complete one individual semi-structured qualitative interview.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Cabotegravir tablets
    30 mg tablets
  • Drug: TDF/FTC tablets
    300 mg/200 mg fixed-dose combination tablets
  • Drug: TDF/FTC placebo tablets
  • Drug: CAB placebo tablets
  • Drug: CAB LA
    Administered as one 3 mL (600 mg) IM injection in the gluteal muscle at two time points 4 weeks apart and every 8 weeks thereafter
  • Drug: Placebo for CAB LA
    Administered as one 3 mL IM injection in the gluteal muscle at two time points 4 weeks apart and every 8 weeks thereafter
Study Arms  ICMJE
  • Experimental: Arm A
    In Step 1, participants will receive daily oral CAB and daily oral TDF/FTC placebo for 5 weeks. In Step 2, participants will receive CAB LA and daily oral TDF/FTC placebo. In Step 3, participants will receive daily oral TDF/FTC no later than 8 weeks after the last injection, for up to 48 weeks.
    Interventions:
    • Drug: Cabotegravir tablets
    • Drug: TDF/FTC tablets
    • Drug: TDF/FTC placebo tablets
    • Drug: CAB LA
  • Experimental: Arm B
    In Step 1, participants will receive daily oral TDF/FTC and daily oral CAB placebo for 5 weeks. In Step 2, participants will receive daily oral TDF/FTC and placebo for CAB LA. In Step 3, participants will receive daily oral TDF/FTC no later than 8 weeks after the last injection, for up to 48 weeks.
    Interventions:
    • Drug: TDF/FTC tablets
    • Drug: CAB placebo tablets
    • Drug: Placebo for CAB LA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 21, 2016)
4500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2022
Estimated Primary Completion Date March 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • MSM and TGW, 18 years or older at the time of screening (male at birth)
  • Willing to provide informed consent for the study
  • At high risk for sexually acquiring HIV infection based on self-report of at least one of the following:

    • Any condomless receptive anal intercourse in the 6 months prior to enrollment (condomless anal intercourse within a monogamous HIV seronegative concordant relationship does not meet this criterion)
    • More than five partners in the 6 months prior to enrollment (regardless of condom use and HIV serostatus, as reported by the enrollee)
    • Any stimulant drug use in the 6 months prior to enrollment
    • Rectal or urethral gonorrhea or chlamydia or incident syphilis in the 6 months prior to enrollment
    • SexPro score of less than or equal to 16 (U.S. sites only)
  • In general good health, as evidenced by the following laboratory values, which must be from specimens obtained within 45 days prior to study enrollment:

    • Non-reactive / negative HIV test results. More information on this criterion can be found in the protocol.
    • Hemoglobin greater than 11 g/dL,
    • Absolute neutrophil count greater than 750 cells/mm^3
    • Platelet count greater than or equal to 100,000/mm^3
    • Calculated creatinine clearance greater than or equal to 60 mL/minute using the Cockcroft-Gault equation (use sex at birth for calculation)

      • Although not protocol exclusionary, sites should carefully consider the advisability of enrolling participants with calculated creatinine clearance between 60-70 mL/min, as limited changes in creatinine clearance during study conduct will lead to protocol-mandated product holds and may alter the risk-benefit considerations of study participation
    • Alanine aminotransferase (ALT) less than 2 times the upper limit of normal (ULN)
    • Total bilirubin less than or equal to 2.5 times ULN
    • Hepatitis B virus (HBV) surface antigen (HBsAg) negative
    • Hepatitis C virus (HCV) Ab negative
    • No Grade 3 or higher laboratory abnormalities on any laboratory tests obtained at screening, including tests obtained as part of a panel of tests ordered to obtain the protocol-required laboratory test results.
  • 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)
  • Willing to undergo all required study procedures

Exclusion Criteria:

  • One or more reactive or positive HIV test result at Screening or Enrollment, even if HIV infection is not confirmed
  • Active or recent use of any illicit intravenous drugs ("recent" defined as in the 90 days prior to enrollment)
  • Co-enrollment in any other interventional research study or other concurrent studies that may interfere with this study (as provided by self-report or other available documentation. Exceptions may be made if appropriate after consultation with the CMC.)
  • Past or current participation in HIV vaccine trial. An exception will be made for participants that can provide documentation of receipt of placebo (not active arm).
  • 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 intramuscular (IM) injections, per the discretion of the Investigator of Record. Mild skin conditions may not be exclusionary at the discretion of the Investigator of Record (IoR) or designee in consultation with the CMC
  • Has a tattoo or other dermatological condition overlying the buttock region which in the opinion of the IoR or designee, in consultation with the CMC, may interfere with interpretation of injection site reactions
  • 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)
  • Coagulopathy (primary or iatrogenic) which would contraindicate IM injection (concomitant anticoagulant or anti-platelet therapy use should be discussed with the CMC)
  • Active or planned use of prohibited medications as described in the Investigator's Brochure or listed in the Study Specific Procedures (SSP) Manual (provided by self-report, or obtained from medical history or medical records). In particular, future use of TDF/FTC at any point during the study.
  • Known or suspected allergy to study product components (active or placebo), including egg or soy products (egg and soy products are contained in Intralipid)
  • Surgically-placed or injected buttock implants or fillers, per self-report. Contact the CMC for guidance regarding questions about individual cases.
  • Alcohol or substance use that, in the opinion of the study investigator, would jeopardize the safety of the participant on study (e.g., provided by self-report, or found upon medical history and examination or in available medical records).
  • History of seizure disorder, per self-report
  • QTc interval (B or F) greater than 500 msec
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Listed Location Countries  ICMJE Argentina,   Brazil,   Peru,   South Africa,   Thailand,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02720094
Other Study ID Numbers  ICMJE HPTN 083
20725 ( Registry Identifier: DAIDS ES )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • ViiV Healthcare
  • Gilead Sciences
Investigators  ICMJE
Study Chair: Raphael J. Landovitz, MD, MSc University of California, Los Angeles
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP