Injectable Cabotegravir Compared to TDF/FTC For PrEP in HIV-Uninfected Men and Transgender Women Who Have Sex With Men
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| ClinicalTrials.gov Identifier: NCT02720094 |
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Recruitment Status :
Active, not recruiting
First Posted : March 25, 2016
Results First Posted : November 24, 2023
Last Update Posted : March 13, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HIV Infections | Drug: Cabotegravir Oral Tablet Drug: TDF/FTC tablets Drug: Placebo for TDF/FTC tablets Drug: Placebo for cabotegravir oral tablet Drug: CAB LA Drug: Placebo for CAB LA | Phase 2 Phase 3 |
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 be followed for a total of 4 years.
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 to Week 153.
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 to Week 153.
In Step 3, all participants (Arms A and B) will receive daily oral TDF/FTC tablets starting at Week 153 (last day of Step 2)/Day 0 (first day of Step 3) and continue for 48 weeks.
Participants will attend up to 47 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 083-01 is a sub-study of HPTN 083. The purpose of this study is to evaluate the safety, tolerability, and acceptability of CAB LA for the prevention of HIV among adolescent males. Participants will receive oral CAB for 5 weeks, followed by 29 weeks on CAB LA, then quarterly visits for 48 weeks after final injection. All participants who have received at least one injection will be followed for 48 weeks after their last injection. Total study duration per participant will be approximately 21 months.
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 4570 participants |
| 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 For Pre-Exposure Prophylaxis in HIV-Uninfected Men and Transgender Women Who Have Sex With Men |
| Study Start Date : | December 2016 |
| Actual Primary Completion Date : | May 14, 2020 |
| Estimated Study Completion Date : | July 1, 2024 |
| Arm | Intervention/treatment |
|---|---|
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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 to Week 153. In Step 3, participants will receive daily oral TDF/FTC starting at Week 153 and for 48 weeks.
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Drug: Cabotegravir Oral Tablet
30 mg tablet
Other Name: Oral cabotegravir Drug: TDF/FTC tablets 300 mg/200 mg fixed-dose combination tablets
Other Name: Truvada Drug: Placebo for TDF/FTC tablets Other Name: Placebo for Truvada 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
Other Names:
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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 to Week 153. In Step 3, participants will receive daily oral TDF/FTC starting at Week 153 and for 48 weeks.
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Drug: TDF/FTC tablets
300 mg/200 mg fixed-dose combination tablets
Other Name: Truvada Drug: Placebo for cabotegravir oral tablet Other Name: Placebo for oral cabotegravir 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
Other Name: Placebo for long acting cabotegravir |
- Number of Participants With Documented Incident HIV Infections During Steps 1 and 2 [ Time Frame: HIV tests at enrollment, weeks 2, 4, 5, every injection visit (every 8 weeks) and every safety visit (2 weeks after each injection visit). Analyzed through week 153 or the date of DSMB decision to unblind all participants, whichever is earliest. ]All HIV infections included in this analysis have been reviewed and confirmed by an independent, blinded Endpoint Adjudication Committee (EAC).
- Number of Participants Experiencing Grade 2 or Higher Clinical and Laboratory Adverse Events [ Time Frame: Treatment emergent AE* measured with onset date through participant's last study visit, or the date of DSMB decision to unblind all participants, whichever is earliest. Assessed at each visit (injections visits q 8 weeks and safety visits q 8 weeks). ]The primary safety endpoint analyses included Grade 2 or higher clinical and laboratory AEs during Steps 1 and 2.
- Number of Participants With Documented Incident HIV Infections in Step 2 [ Time Frame: HIV tests at enrollment, weeks 2, 4, 5, every injection visit (every 8 weeks) and every safety visit (2 weeks after each injection visit). Analyzed through week 153 oror the date of DSMB decision to unblind all participants, whichever is earliest. ]Evaluate incident HIV-1infections occurring only during Step 2, using the Injection Step 2 Efficacy population
- Changes From Baseline in Creatinine and Creatinine Clearance Levels [ Time Frame: Reported week 57 (injection visit #8) and week 105 (injection visit #14) ]Change from baseline at each visit is the difference between the creatine (and creatinine clearance) value as measured on the date of visit, compared to the value as measured at the enrollment visit.
- Number of Participants With Grade 3 or 4 Liver-related Adverse Events (AEs) [ Time Frame: Treatment emergent AE measured with onset date through participant's last study visit, or the date of DSMB decision to unblind all participants, whichever is first. Assessed at each visit. (Injection visits q 8 weeks and safety visits q 8 weeks) ]Laboratory assessment of alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBili, creatine phosphokinase (CPK), or clinical assessment of jaundice/icterus.
- Incidence of Resistance Mutations to Study Products (Including But Not Limited to K65R, M184V/I, Q148R) Among Seroconverters [ Time Frame: Measured from date of detection of infection, up to 4 years after study entry, with timing/intervals as determined by the HPTN laboratory center ]Frequency of the detection of specific viral mutations known to confer resistance to specific classes of antiviral drugs as identified in specimens collected from infected participants during follow-up after HIV infection.
- Changes in Weight From Baseline [ Time Frame: Reported through the week 153 injection, or the date of DSMB decision to unblind all participants, whichever is earliest. Collected at each injection visit (every 8 weeks). ]Change in weight from baseline is the difference between the weight (kg) as collected at each study visit and the weight collected at the enrollment visit.
- Changes in Blood Pressure From Baseline [ Time Frame: Reported through the week 153 injection, or the date of DSMB decision to unblind all participants, whichever is earliest. Assessed at each injection visit (every 8 weeks). ]Change in blood pressure from baseline is the difference between the blood pressure as collected at each study visit and the blood pressure collected at the enrollment visit. Reported in separate tables for systole and diastole.
- Changes in Pulse Rate From Baseline [ Time Frame: Reported through the week 153 injection, or the date of DSMB decision to unblind all participants, whichever is earliest. Assessed at each injection visit (every 8 weeks). ]Change in pulse rate from baseline is the difference between the pulse rate as collected at each study visit and the pulse rate collected at the enrollment visit.
- Changes in Fasting Glucose Levels From Baseline [ Time Frame: Assessed at weeks 57 and 105. ]Changes in fasting glucose levels from baseline at week 57 and week 105 based on laboratory evaluations.
- Changes in Fasting Lipid Profile From Baseline [ Time Frame: Assessed at weeks 57 and 105. ]Changes in fasting lipid profile from baseline at week 57 and week 105 based on laboratory evaluations.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
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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)
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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
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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). Note: Past participation in a monoclonal antibody study is not exclusionary, effective as of Version 1.0 of HPTN 083.
- 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
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
| Study Chair: | Raphael J. Landovitz, MD, MSc | University of California, Los Angeles |
Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):
| Responsible Party: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT02720094 |
| Other Study ID Numbers: |
HPTN 083 20725 ( Registry Identifier: DAIDS ES ) |
| First Posted: | March 25, 2016 Key Record Dates |
| Results First Posted: | November 24, 2023 |
| Last Update Posted: | March 13, 2024 |
| Last Verified: | March 2024 |
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Pre-Exposure Prophylaxis PrEP |
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HIV Infections Blood-Borne Infections Communicable Diseases Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Genital Diseases Urogenital Diseases Immunologic Deficiency Syndromes |
Immune System Diseases Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination Cabotegravir Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Anti-HIV Agents Anti-Retroviral Agents HIV Integrase Inhibitors Integrase Inhibitors |