Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Males

Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Males - A Sub-study of HPTN 083

This study will establish the minimum safety, tolerability and acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an adolescent population, potentially transforming the field of HIV prevention for young people.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Cabotegravir (CAB) tablet; Drug: CAB LA; Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet

Detailed Description

The purpose of this study is to establish the minimum safety, tolerability and acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an adolescent population, potentially transforming the field of HIV prevention for young people.

This study will enroll healthy, HIV-uninfected adolescents assigned male at birth, including men who have sex with men (MSM), transgender women (TGW), and gender non-conforming people. The total participant commitment for the entire study is approximately 1.5 years.

This study will take place in three steps. In Step 1, participants will receive daily oral CAB tablets for 5 weeks. In Step 2, participants will receive a series of five intramuscular (IM) injections of CAB LA, administered at 8-week intervals after a 4-week loading dose (injections at Weeks 5, 9, 17, 25 & 33). A safety visit will follow each injection to ascertain safety data, including injection site reactions. In Step 3, all participants who have received at least one injection will be followed quarterly (every 3 months) for 48 weeks after their last injection. Participants will receive oral TDF/FTC for daily use for 48 weeks or may be provided the opportunity to enroll in a local open label study of CAB, if available.

Participants will attend about 18 study visits throughout the study. Visits may include physical examinations, blood collection, urine collection, rectal and oral pharyngeal swab collection, risk reduction and adherence counseling, and behavioral or acceptability assessments.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver ATN CRS
  • Illinois
    • Chicago, Illinois, United States, 60612
      • John H. Stroger Jr. Hosp. of Cook County ATN CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • The Fenway Institute ATN CRS
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hosp. ATN CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Assigned male at birth (includes MSM, TGW, and gender non-conforming people)
• At enrollment, aged below 18 years
• At enrollment, body weight ≥ 35 kg (77 lbs.)
• Willing to provide informed consent for the study
• Self-reported sexual activity with a male in the past 12 months

• In general, good health, as evidenced by the following laboratory values

  • Non-reactive/negative HIV test results
  • Absolute neutrophil count > 799 cells/mm3
  • Platelet count ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 11g/dL
  • Calculated creatinine clearance ≥ 60 mL/minute using modified Schwartz equation (≤ grade 2)
  • Alanine aminotransferase (ALT) < 2.0 times the upper limit of normal (ULN) and total bilirubin (Tbili) ≤ 2.5 x ULN
  • Hepatitis B virus (HBV) surface antigen (HBsAg) negative and accepts vaccination
  • Hepatitis C virus (HCV) Antibody negative
• Willing to undergo all required study procedures
• If currently on pre-exposure prophylaxis (PrEP) from a non-study source, willing to stop said PrEP prior to enrollment and agree to switch to oral CAB for the lead-in period and CAB LA injections.

Exclusion Criteria:

• Co-enrollment in any other HIV interventional research study or other concurrent studies which may interfere with this study (as provided by self-report or other available documentation)
• Past or current participation in HIV vaccine trial with exception for participants who can provide documentation of receipt of placebo
• Exclusively had sex with biological females in lifetime
• In the last 6 months (at the time of screening): active or planned use of any substance which would, in the opinion of the site investigator, would hinder study participation (including herbal remedies), as described in the Investigator's Brochure (IB) or listed in the Study Specific Procedures (SSP), and/ or Protocol Section 4.4
• Known history of 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
• Tattoo or other dermatological condition overlying the buttock region that 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)
• Known history of clinically significant bleeding
• Surgically-placed or injected buttock implants or fillers, per self-report. Contact the CMC for guidance regarding questions about individual cases
• A history of seizure disorder, per self-report
• Medical, social, or other condition that, in the opinion of the site investigator, would interfere with the conduct of the study or the safety of the participant (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
• Plans to move out of the geographic area within the next 18 months or otherwise unable to participate in study visits, according to the site investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CAB LA; In Step 1, participants will receive one CAB tablet orally every day for 5 weeks. In Step 2, participants will receive an intramuscular (IM) injection of CAB LA at Weeks 5, 9, 17, 25, and 33. In Step 3, participants will receive a TDF/FTC tablet orally every day for 48 weeks or may be offered the opportunity to join an open label CAB study instead, if such a study is being implemented in their area at the time.

Drug: Cabotegravir (CAB) tablet; 30 mg 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: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet; 300 mg/200 mg fixed-dose combination tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Endpoint: Proportion of Participants Experiencing Any Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities Among Participants Who Receive at Least One Injection of CAB LA.	Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities (reported as adverse events) from the first injection visit to 8 weeks after the last Step 2 injection visit, or Week 41, whichever comes first.	Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
Tolerability Endpoint: Proportion of Participants Who Receive at Least 1 Injection and Who Discontinue Receiving Injections Prior to the Full Course of Injections Due to Intolerability of Injection, Frequency of Injections or Burden of Study Procedures.	Number and percent of participants who receive at least 1 injection and who discontinue receiving injections prior to the full course of injections due to intolerability of injection or burden of study procedures. Reasons for intolerability may include: Injection site reaction; Burden of study procedureParticipant refused further participationParticipant is unwilling or unable to comply with required study proceduresParticipant refused further study product useParticipant unable to adhere to visit schedule	Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future.	Definition of completing all scheduled injections for participants who are confirmed HIV positive or discontinue product due to the following reasons: Death; Early study closure; HBV infection During Step 2: Both enrolled and injection populations: completed all injections whose target window closed prior to death/seroconversion/product discontinuation date	Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study	Data from steps 1, 2, and 3 will be included. The number of cases of drug resistance will be summarized. All cases of drug resistance among incident HIV infections will be described.	Measured through participant's last study visit, up to approximately 1.5 years after study entry.
Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90)	CAB drug concentrations will be measured in plasma to generate CAB-LA concentration-time profiles among study participants. Measurements will occur at study visits during the injection phase of the study as well as during the pharmacologic "tail" phase. Count of participants for injection visits in which a participant remains above the 1x (0.166 mcg/mL), 4x (0.664 mcg/mL) and 8x (1.33 mcg/mL) PA-IC90.Concentrations above the 3 PA-IC90 are associated with rectal protection in a non-human primate study, and concentrations above the 8x PA-IC90 are expected to be associated with protection in humans.	Measured from the participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41
Measure Study Product Concentrations in Enrolled Participants With HPTN Laboratory Center (LC) Confirmed HIV Infection Throughout Study.	For infections occurring prior to (or on the first day of) Step 3, we will include visit level plasma CAB concentrations, for individual seroconverters. For infections occurring after the start of Step 3, we will include visit level plasma CAB concentrations as well as concentrations of TFV and TFV-DP (if applicable).	Measured through seroconverter's first Oral visit up through end of study participation (step1, 2, 3)
Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and LaboratoryAbnormalities in the Oral Phase and the Aggregate Oral and Injection Phases	Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities from: enrollment to week 5 (oral phase (step 1), including interim visits).; enrollment to 8 weeks following the last injection received (aggregate over oral + injection phases (step 1-step 2) including interim visits)	Measured through participant's first oral visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
Proportion of Participants Receiving One or More Injections Who Experience Grade 2 or Higher Clinical AEs and Laboratory Abnormalities From Initial Injection to 36 Weeks Later.	Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities from the first injection visit to approximately 36 weeks later regardless of whether participants received all 5 injections.	Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
Proportion of Injection Visits That Occurred "On-time".	Number and percentage of injections given, using the number of injections expected as the denominator. while the number and percent of injection visits (up to 5 per participant) that occur "on-time", using the number of injections given as the denominator. This will be presented along with the total number and percent of injections given, among all intended injections (i.e. 5 injections per participant). Those who have been terminated, are HIV infected, or have permanently discontinued study products at the time of visit will be excluded from the number of expected injections.	Measured through participant's last step 2 injection.
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period	Counts of sexual partners will be summarized (mean and sd) at enrollment and each regular Step 1 and Step 2 follow-up visit (W4, W5, W9, W17, W25, W33).	Measured through participant's first oral visit up to last Step 2 injection visit.
Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period	Counts of episodes of anal intercourse without a condom will be summarized (mean and sd) at enrollment and each regular Step 1 and Step 2 follow-up visit (W4, W5, W9, W17, W25, W33).	Measured through participant's first oral visit up to the last Step 2 injection visit.

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Sybil Hosek, PhD, Stroger Hospital of Cook County; Study Chair: Lynda Stranix-Chibanda, MBChB, MMED, University of Zimbabwe College of Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: December 30, 2020
• First Posted (Actual): December 31, 2020

Study Record Updates

• Last Update Posted (Estimated): May 20, 2025
• Last Update Submitted That Met QC Criteria: May 16, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: PrEP; Pre-Exposure Prophylaxis
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Emtricitabine; Cabotegravir
• Other Study ID Numbers: HPTN 083-01; 38654 (Registry Identifier: DAIDS ES)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No