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

NCT04692077 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: HPTN 083-0138654
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

HIV Infections

Keywords

Pre-Exposure Prophylaxis; PrEP

Outcome Measures

Primary Outcomes (3)

• 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: 1. Injection site reaction 2. Burden of study procedure 1. Participant refused further participation 2. Participant is unwilling or unable to comply with required study procedures 3. Participant refused further study product use 4. Participant 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 Outcomes (8)

• Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90)

  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.

  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

  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.

  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".

  Measured through participant's last step 2 injection.

Study Arms (1)

CAB LA

EXPERIMENTAL

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; Drug: CAB LA; Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet

Interventions

Cabotegravir (CAB) tablet DRUG

30 mg tablets

CAB LA

CAB LA DRUG

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.

CAB LA

Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet DRUG

300 mg/200 mg fixed-dose combination tablets

CAB LA

Eligibility Criteria

• Age: Up to 17 Years
• Gender Eligibility Details: Assigned male at birth (includes MSM, TGW, and gender non-conforming people)
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

University of Colorado Denver ATN CRS

Aurora, Colorado, 80045, United States

Location

John H. Stroger Jr. Hosp. of Cook County ATN CRS

Chicago, Illinois, 60612, United States

Location

The Fenway Institute ATN CRS

Boston, Massachusetts, 02215, United States

Location

St. Jude Children's Research Hosp. ATN CRS

Memphis, Tennessee, 38105, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir; Tenofovir; Emtricitabine; Tablets

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: HPTN Statistical Manager
• Organization: HPTN Statistical & Data Management Center

HPTN-Data-Access@scharp.org

+1 (206) 667-4004

Study Officials

• Sybil Hosek, PhD

  Stroger Hospital of Cook County

  STUDY CHAIR

• Lynda Stranix-Chibanda, MBChB, MMED

  University of Zimbabwe College of Health Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: December 31, 2020
• Study Start: February 19, 2020
• Primary Completion: July 7, 2023
• Study Completion: July 7, 2023
• Last Updated: May 20, 2025
• Results First Posted: January 29, 2025

Record last verified: 2025-05

Locations

US (4)