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Trial record 1 of 1 for:    HPTN083
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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

This study is currently recruiting participants.
Verified October 2017 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02720094
First Posted: March 25, 2016
Last Update Posted: October 3, 2017
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.
Collaborators:
ViiV Healthcare
Gilead Sciences
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
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).

Condition Intervention Phase
HIV Infections Drug: Cabotegravir tablets Drug: TDF/FTC tablets Drug: TDF/FTC placebo tablets Drug: CAB placebo tablets Drug: CAB LA Drug: Placebo for CAB LA Phase 2 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 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

Resource links provided by NLM:


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 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 4500
Study Start Date: December 2016
Estimated Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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
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.
Drug: TDF/FTC tablets
300 mg/200 mg fixed-dose combination tablets
Drug: CAB placebo tablets Drug: Placebo for CAB LA
Administered as one 3 mL (600 mg) injection in the gluteal muscle at two time points 4 weeks apart and every 8 weeks thereafter

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
    • 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
  • 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
  Contacts and Locations
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): NCT02720094


  Show 43 Study Locations
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
ViiV Healthcare
Gilead Sciences
Investigators
Study Chair: Raphael J. Landovitz, MD, MSc University of California, Los Angeles
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02720094     History of Changes
Other Study ID Numbers: HPTN 083
20725 ( Registry Identifier: DAIDS ES )
First Submitted: March 21, 2016
First Posted: March 25, 2016
Last Update Posted: October 3, 2017
Last Verified: October 2017

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pre-Exposure Prophylaxis
PrEP

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
Tenofovir
Emtricitabine
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