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

NCT04824131 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: HPTN 084-0138655
• Study Type: interventional
• Target: 55
• Locations: 3 countries
• Sites: 3

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

Outcome Measures

Primary Outcomes (3)

• Count and Percentage 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

• Tolerability Endpoint: Percentage 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 i. Participant refused further participation ii. Participant is unwilling or unable to comply with required study procedures iii. Participant refused further study product use iv. 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

• Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future.

  Number and percent of participants who complete all scheduled injections: Defined as completing all scheduled injections for participants who are confirmed pregnant, confirmed HIV seroconverted, or discontinue product due to the following reasons: * Death * Early study closure * HBV infection During Step 1: Enrolled population: completed all 0 of 0 scheduled injections Injection population: not applicable, did not receive injection During Step 2: Both enrolled and injection: completed all injections whose target window closed prior to pregnancy/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

Secondary Outcomes (7)

• Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit

  Measured through participant's first Oral visit up to, 10 weeks after the last Step 2 injection visit or week 41

• Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit.

  Measured through weeks 5, 6, 9, 10, 17, 18, 25, 26, 33, 34, 41 (33 +8)

• Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and Laboratory Abnormalities 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

• Number and Percent of Injection Visits That Occurred "On-time"

  Measured through participant's last study visit, up to approximately 1.5 years after study entry.

• Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period

  Measured through participant's study visit, up to Week 48 from enrollment.

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 join an open-label extension CAB study in their area, if available.

Drug: Oral cabotegravir (CAB); Drug: CAB LA; Drug: Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)

Interventions

Oral cabotegravir (CAB) 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

Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) DRUG

300 mg/200 mg fixed-dose combination tablets

CAB LA

Eligibility Criteria

• Age: Up to 17 Years
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Assigned female at birth
• At enrollment, below 18 years of age
• At enrollment, body weight ≥ 35 kg (77 lbs.)
• Willing and able to provide informed assent/consent for the study and/or able to obtain written parental/guardian informed consent
• Self-reported sexual activity with a male (oral, anal or vaginal) in the past 12 months
• Willing and able to undergo all study procedures
• 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/mm3,
• Hemoglobin ≥ 11g/dL,
• Calculated creatinine clearance ≥ 60 mL/minute using the modified Schwartz equation,
• Alanine aminotransferase (ALT) \< 2.0 times the upper limit of normal (ULN) (≤ grade 1) 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

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 use which would, in the opinion of the site investigator, interfere with 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
• 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 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
• Pregnant or currently breastfeeding at the time of screening or intends to become pregnant and/or breastfeed while on study

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• ViiV Healthcare: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (3)

Ward 21 CRS

Johannesburg, Gauteng, 2001, South Africa

Location

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

Kampala, 23491, Uganda

Location

Spilhaus CRS

Harare, Zimbabwe

Location

Related Publications (1)

• Stranix-Chibanda L, Hamilton EL, Ngo J, Jiao Y, Hanscom B, Choudhury RP, Agyei Y, Piwowar-Manning E, Marzinke M, Delany-Moretlwe S, Mgodi N, Siziba B, Naidoo I, Gati Mirembe B, Kamira B, McCoig C, Adeyeye A, Spiegel HML, Hosek S; HPTN 084-01 Protocol Team. Safety, tolerability, and acceptability of long-acting injectable cabotegravir for HIV prevention in cisgender female adolescents (HPTN 084-01): a single-arm, open-label, phase 2b trial. Lancet HIV. 2025 Apr;12(4):e252-e260. doi: 10.1016/S2352-3018(24)00310-2. Epub 2025 Mar 12.

  PMID: 40088909 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir; Tenofovir; Emtricitabine

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

Results Point of Contact

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

HPTN-Data-Access@scharp.org

1206-667-4004

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: January 6, 2021
• First Posted: April 1, 2021
• Study Start: November 4, 2020
• Primary Completion: January 10, 2023
• Study Completion: January 10, 2023
• Last Updated: December 3, 2024
• Results First Posted: July 30, 2024

Record last verified: 2024-11

Locations

UG (1); ZA (1); ZI (1)