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HIV InfectionsPhase 2NCT04824131

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

A Phase 2 study testing Oral cabotegravir (CAB), CAB LA and Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 17 years, women onlyHealthy volunteers can take part
Conditions the study is for
HIV Infections
What is being tested?
Oral cabotegravir (CAB), CAB LA and Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
3 sitesin 3 countries
Study dates
4 Nov 2020to 10 Jan 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 17 years
  • Women only
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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
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  • 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
  • Must have a negative beta human chorionic gonadotropin (βHCG) pregnancy test (sensitivity of ≤ 25 mIU/mL) performed (and results known) on the same day as Enrollment and before initiating study product
  • Must agree to use a reliable form of long acting contraception, during the trial and for 48 weeks after stopping the long acting injectable, or 30 days after stopping oral study product, from the list below:
  • Intrauterine device (IUD) or intrauterine system (IUS) that meets <1% failure rate as stated in the product label
  • Hormone-based contraceptive that meets <1% failure rate when used consistently and correctly as stated in the product label (implants or injectables only; this excludes combined oral contraception)
  • If currently on 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.
  • HIV-uninfected, based on HIV test results obtained at Screening and at the Enrollment visit. All HIV test results from the Screening visit must be obtained and must all be negative/non-reactive. This includes testing for acute HIV infection, which must be performed within 14 days of Enrollment. Individuals who have one or more reactive or positive HIV test result(s) will not be enrolled, even if subsequent confirmatory testing indicates that they are not HIV-infected (see SSP Manual).

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

South Africa1 site

  • Ward 21 CRS

    Johannesburg, Gauteng, 2001

Other trials in South Africa

Uganda1 site

  • MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

    Kampala, 23491

Other trials in Uganda

Zimbabwe1 site

  • Spilhaus CRS

    Harare

Other trials in Zimbabwe

About this study

Official title: Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Females - A Sub-study of HPTN 084

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.

Read the detailed description

This study will enroll sexually-active, healthy, HIV-uninfected adolescents assigned female sex at birth. 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 join and open-label extension CAB study in their area, if available.

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

Conditions
HIV Infections
Being tested
Oral cabotegravir (CAB), CAB LA, Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Oral cabotegravir (CAB)Drug

    30 mg tablets

  • CAB LADrug

    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

  • Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)Drug

    300 mg/200 mg fixed-dose combination tablets

Study groups in NCT04824131
Study groupRoleWhat they receive
CAB LAExperimentalIn 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.
Receives: Drug: Oral cabotegravir (CAB); Drug: CAB LA; Drug: Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41

  2. 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: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41

  3. 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: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41

Secondary outcomes (7)

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

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

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

    CAB drug concentrations will be measured throughout the study, and the study team will characterize variability in concentrations at each visit by determining mean concentrations, as well as associated deviations.

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

  3. 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

    Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities from:

    1. enrollment to week 5 (oral phase (step 1), including interim visits).
    2. enrollment to 8 weeks following the last injection received (aggregate over oral + injection phases (step 1-step 2) including interim visits)

    Measured: Measured through participant's first Oral visit up to, 8 weeks after the last Step 2 injection visit or week 41

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

    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).

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

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

    We will use generalized estimating equations (GEE) with robust variance to model change in self-reported sexual behavior from enrollment (W0) to follow up visits (W4, W5, W9, W17, W25, W33, W+12, W+24, W+36, W+48), with an indicator variable for all on-study visits (i.e. enrollment visit = 0) to measure change in the outcome behavior. We will model count outcomes (number of sexual partners) using a poisson model.

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

  6. Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period

    We will use generalized estimating equations (GEE) with robust variance to model change in self-reported sexual behavior from enrollment (W0) to follow up visits (W4, W5, W9, W17, W25, W33, W+12, W+24, W+36, W+48), with an indicator variable for all on-study visits (i.e. enrollment visit = 0) to measure change in the outcome behavior. We will model count outcomes (number of episodes of vaginal sex without a condom) using a poisson model and binary outcomes (any episodes of anal sex without a condom) using a logistic model.

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2021
  2. Study start4 Nov 2020
  3. Primary completion10 Jan 2023
  4. Study completion10 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04824131
Sponsor's protocol ID
HPTN 084-01
Other IDs
38655
Status last verified
Nov 2024
First submitted
6 Jan 2021
Last updated
3 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 40088909

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Oral cabotegravir (CAB), CAB LA and Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in South Africa, Uganda, Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04824131, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2024.

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