Clinical trial NCT06741397: A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of a New Formulation of Cabotegravir Long-Acting Administered Intramuscularly in a 4-month Dosing Interval (Q4M)
Official title: A Phase 2b Single Arm, Repeat Dose Study to Evaluate the Pharmacokinetic Profile, Safety, and Tolerability of A New Formulation of Cabotegravir LA Injected Intramuscularly Q4M in Adolescent and Adult Participants at Risk of HIV Acquisition
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HIV Infections
Keywords: Cabotegravir (CAB)
New formulation of CAB LA
CAB LA
HIV
4-month dosing interval (Q4M)
Safety
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2024-12-19
Enrollment: 228
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a new formulation of Cabotegravir (CAB) dosed every 4-months (Q4M) for pre-exposure prophylaxis (PrEP) in participants at risk of HIV-1 acquisition.


Eligibility criteria: Inclusion Criteria:

1. At the time of obtaining informed consent, adolescent and adult participants weighing at least 35 kg.
2. Participants must have a nonreactive HIV test at Screening (rapid test, nonrapid HIV immunoassay, and HIV RNA) and enrollment (a rapid test, nonrapid HIV immunoassay, and HIV RNA).
3. Participants who are at risk of acquiring HIV, defined as having had anal or vaginal sex in the past 6 months.
4. Participants who are overtly healthy as determined by medical evaluation by a responsible and experienced physician, including medical history, physical examination, laboratory tests and cardiac monitoring at the time of screening.
5. No alcohol or substance use that, in the opinion of the study investigator and medical monitor, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records).
6. Participants who have received oral PrEP are eligible, but they must discontinue oral PrEP within 10 days of Day 1 visit.
7. Male or female at birth, (transgender individuals are not excluded). Contraceptive use should align with local regulations. Participants assigned female at birth must not be pregnant or breastfeeding and must either not be of childbearing potential (POCBP) or use highly effective contraception. A POCBP must have a negative pregnancy test within 30 days before dosing.
8. Participants must be \>=16 years old, of legal age to consent to sexual intercourse, and capable of giving written informed consent. Adolescents must provide written informed assent/consent and/or obtain parental/guardian consent if not of legal age, as per site SOPs and IRB/EC policies.

Exclusion Criteria:

1. One or more reactive or positive HIV test results at Screening or Enrollment, even if HIV infection was not confirmed.
2. Participants who are breastfeeding or plan to become pregnant or breastfeed during the study.
3. Alanine aminotransferase (ALT) \>=3 times the upper limit of normal (ULN).
4. Evidence of active Hepatitis B virus (HBV) infection.

   * Participants positive for HBsAg or HBV DNA are excluded.
   * Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
5. Unstable liver disease, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
6. History of clinically relevant hepatitis within last 6 months.
7. Known history of liver cirrhosis with or without viral hepatitis co-infection.
8. Participants with Hepatitis C virus (HCV) co-infection will be allowed entry into this study if:

   * Liver enzymes meet entry criteria.
   * HCV Disease has undergone appropriate work-up, and is not advanced, and will not require treatment prior to the primary endpoint (e.g., Month 13).
   * In the event that recent biopsy or imaging data is not available or inconclusive, the Fibrosis 4 (Fib-4) score will be used to verify eligibility:

     i. Fib-4 score greater than (\>) 3.25 is exclusionary. ii. Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation. Fibrosis 4 score Formula: (Age x AST) / (Platelets x (sqr \[ ALT\]) It is approved by the Medical Monitor.
9. Creatinine clearance of \<30 mL/min/1.73 m2 via CKD-EPIcr_R (2021) method.
10. Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
11. Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 \[triglycerides or lipid abnormalities\].
12. Participants determined by the Investigator to have a high risk of seizures, A participant with a prior history of seizure may be considered for enrolment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment.
13. Participant is currently participating in or has participated in a study with a compound or device that is not commercially available within 30 days of signing informed consent, unless permission from the Medical Monitor is granted.
14. Presence of any history of allergy/sensitivity to any of the study drug.
15. Inflammatory skin conditions that compromise the safety of IM injections, per the discretion of the investigator.
16. Participant has an implant/enhancement (including fillers) at the area of proposed injection (e.g., gluteus medius); or tattoo or other dermatological condition overlying the area for IM (e.g., gluteus medius) or any other area which may significantly interfere with interpretation of injection site reactions.
17. Current or anticipated need for chronic anti-coagulants or active coagulopathy (primary or iatrogenic) which would contraindicate IM injection.
18. Ongoing or clinically relevant pancreatitis.
19. Clinically significant cardiovascular disease or history of clinically significant cardiovascular disease.
20. All participants will be screened for STIs (e.g., chlamydia, gonorrhea, trichomoniasis, syphilis). Participants with untreated infections are excluded. Participants may be rescreened at least 24 hours after completion of STI treatment.
21. History or presence of sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
22. Ongoing uncontrolled malignancy is excluded, whereas participants who have controlled localized malignancies may be included on agreement between the investigator and the Medical Monitor.
23. Participants who in the investigator's judgment, poses a significant suicidality risk.
24. Any pre-existing physical or mental condition (including substance abuse disorder) which, in the opinion of the Investigator or the medical monitor, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
25. Any condition which, in the opinion of the Investigator or the medical monitor, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive IM medication.
26. Co-enrollment in any other interventional research study or other concurrent studies which may have interfered with this study (as provided by self-report or other available documentation). Exceptions for non-interventional studies may be made if appropriate after consultation with the Medical Monitor.
27. Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
28. Use of antiretroviral therapy (ART) for Postexposure Prophylaxis within the 90 days prior to Day 1.
29. Use of CAB LA for PrEP at any time prior to Screening.
30. Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP.
31. Anticipated need for HCV therapy with interferon or any drugs that have potential for adverse drug:drug interactions with study treatment throughout the entire study period.
32. Treatment with an HIV-1 preventive vaccine within 90 days of Screening.
33. Participant is unlikely to adhere to the study procedures, keep appointments, is planning to relocate during the study, or remain on study through to its conclusion.
34. Participants who are considered high-risk, meeting at least one of the following criteria:

    * Participant who has exchanged condomless sex for goods or money within the past 12 months prior to Screening.
    * Participant who has used recreational intravenous drugs within the past 12 months prior to Screening.
    * Participant who has participated in Chemsex practice (such as the use of cocaine, crack cocaine, methamphetamine, ketamine, 3,4-methlenedioxy-methamphetamine, GHB, mephedrone or prescription drugs apart from those prescribed by a licensed provider) within the past 6 months prior to Screening.
    * Participant with any STI in the last 6 months also reporting any partners for condomless sex.
    * Participant who has condomless sex with a serodiscordant partner who has a detectable viral load or is not on ART.
    * Participant with any other behavior assessed by the investigator as high-risk sexual behavior.
35. Participant has in the last 14 days prior to Screening presented with signs and symptoms, which, in the opinion of the investigator, are suggestive of acute HIV infection. Participants may only be enrolled if clinical suspicion of HIV is ruled out with non-reactive results.
36. Participant becomes a ward of state (e.g., child in care).

Primary outcomes:
measure: CAB trough concentrations for target of 1.05 microgram per milliliter (μg/mL) for men and 1.39 μg/mL for women
timeFrame: From Month 13 to Month 25
Secondary outcomes:
measure: CAB trough concentrations for target of 0.672 μg/mL for men and 0.683 μg/mL for women
timeFrame: At Month 1
measure: CAB trough concentrations for target of 1.05 μg/mL for men and 1.39 μg/mL for women following loading dose
timeFrame: From Month 3 to Month 33
measure: CAB plasma concentrations
timeFrame: At 1-week post dose administration (doses administered at Day 1, Months 1, 3, 5 and 9), at midcycle (Month 2, Month 7, Month 11) and trough (Month 33)
measure: CAB trough concentrations for target of 4x PA-IC90
timeFrame: At Months 1, 3, 5, 9, 13, 17, 21, 25, 29, and 33
measure: Percentage of participants with confirmed incident HIV infections
timeFrame: Up to Month 33
measure: Percentage of participants with Study Medication Satisfaction Questionnaire Status version (SMSQs) results
timeFrame: From Month 1 up to Month 33
measure: Percentage of participants with Adverse events (AEs)
timeFrame: Up to Month 33
measure: Percentage of participants with AEs by severity
timeFrame: Up to Month 33
measure: Percentage of participants with laboratory abnormalities
timeFrame: Up to Month 33
measure: Percentage of participants with laboratory abnormalities by severity
timeFrame: Up to Month 33
measure: Percentage of participants with changes in laboratory parameters
timeFrame: Up to Month 33
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palm Springs
country: United States
facility: GSK Investigational Site
state: California
city: Coral Gables
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: New Orleans
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Berkley
country: United States
facility: GSK Investigational Site
state: Michigan
city: Kansas City
country: United States
facility: GSK Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Valhalla
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
Study officials:
References: