Clinical trial NCT04692077: Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Males
Official title: Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Males - A Sub-study of HPTN 083
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Pre-Exposure Prophylaxis
PrEP
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2020-12-31
Enrollment: 9
Sex: MALE
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
measure: 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.
timeFrame: Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
measure: 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.
timeFrame: 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:
measure: Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90)
timeFrame: Measured from the participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41
measure: Measure Study Product Concentrations in Enrolled Participants With HPTN Laboratory Center (LC) Confirmed HIV Infection Throughout Study.
timeFrame: Measured through seroconverter's first Oral visit up through end of study participation (step1, 2, 3)
measure: 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
timeFrame: Measured through participant's first oral visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
measure: 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.
timeFrame: Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
measure: Proportion of Injection Visits That Occurred "On-time".
timeFrame: Measured through participant's last step 2 injection.
measure: Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period
timeFrame: Measured through participant's first oral visit up to last Step 2 injection visit.
measure: Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period
timeFrame: Measured through participant's first oral visit up to the last Step 2 injection visit.
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: Aurora
country: United States
facility: University of Colorado Denver ATN CRS
state: Colorado
city: Chicago
country: United States
facility: John H. Stroger Jr. Hosp. of Cook County ATN CRS
state: Illinois
city: Boston
country: United States
facility: The Fenway Institute ATN CRS
state: Massachusetts
city: Memphis
country: United States
facility: St. Jude Children's Research Hosp. ATN CRS
state: Tennessee
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: