Clinical trial NCT04824131: Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Females
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: ViiV Healthcare
name: Bill and Melinda Gates Foundation
First posted: 2021-04-01
Enrollment: 55
Sex: FEMALE
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: Inclusion Criteria:

* 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
* 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).

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 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

Primary outcomes:
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.
timeFrame: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41
measure: 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.
timeFrame: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41
measure: 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.
timeFrame: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41
Secondary outcomes:
measure: Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit
timeFrame: Measured through participant's first Oral visit up to, 10 weeks after the last Step 2 injection visit or week 41
measure: Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit.
timeFrame: Measured through weeks 5, 6, 9, 10, 17, 18, 25, 26, 33, 34, 41 (33 +8)
measure: 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
timeFrame: Measured through participant's first Oral visit up to, 8 weeks after the last Step 2 injection visit or week 41
measure: Number and Percent of Injection Visits That Occurred "On-time"
timeFrame: Measured through participant's last study visit, up to approximately 1.5 years after study entry.
measure: Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period
timeFrame: Measured through participant's study visit, up to Week 48 from enrollment.
measure: Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period
timeFrame: Measured through participant's last study visit, up to approximately 1.5 years after study entry.
measure: Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study
timeFrame: Measured through participant's last study visit, up to approximately 1.5 years after study entry.
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Ward 21 CRS
state: Gauteng
city: Kampala
country: Uganda
facility: MU-JHU Research Collaboration (MUJHU CARE LTD) CRS
city: Harare
country: Zimbabwe
facility: Spilhaus CRS
Study officials:
affiliation: Stroger Hospital of Cook County
name: Sybil Hosek, PhD
role: STUDY_CHAIR
affiliation: University of Zimbabwe College of Health Sciences
name: Lynda Stranix-Chibanda, MBChB, MMED
role: STUDY_CHAIR
References: