A Study Evaluating the Pharmacokinetics, Efficacy, Safety and Tolerability of CABENUVA

NCT05601128 | Completed Phase 3 FDA Drug

• 1 other identifier: CAPRI
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of CABENUVA (Long-acting Cabotegravir Plus Long-acting Rilpivirine) in patients with HIV infection and severe renal impairment. This study is considered research and is voluntary.

Conditions

HIV-1-infection; HIV Infections; HIV I Infection

Outcome Measures

Primary Outcomes (12)

• Cabotegravir plasma concentration over time

  Since this is primarily a pharmacokinetics study, this descriptive outcome will demonstrate plasma concentration measures (Ctrough) versus time profiles for CAB LA.

  Month 2 through Month 12 (for Ctrough)

• Cabotegravir plasma concentration over time

  Since this is primarily a pharmacokinetics study, this descriptive outcome will demonstrate plasma concentration measures (Cmax) versus time profiles for CAB LA.

  Month 2 through Month 12 (for Cmax)

• Cabotegravir area under the curve

  Since this is primarily a pharmacokinetics study, this descriptive outcome will demonstrate "Area Under the Curve (AUC)" calculations for CAB LA.

  Month 1through Month 2, Month 5 through Month 6, and Month 10 through Month 12 (for AUC)

• Rilpivirine plasma concentration over time

  Since this is primarily a pharmacokinetics study, this descriptive outcome will demonstrate plasma concentration measures (Ctrough) versus time profiles for RPV LA.

  Month 2 through Month 12 (for Ctrough)

• Rilpivirine plasma concentration over time

  Since this is primarily a pharmacokinetics study, this descriptive outcome will demonstrate plasma concentration measures (Cmax) versus time profiles for RPV LA.

  Month 2 through Month 12 (for Cmax)

• Rilpivirine area under the curve

  Since this is primarily a pharmacokinetics study, this descriptive outcome will demonstrate "Area Under the Curve (AUC)" calculations for RPV LA.

  Month 1through Month 2, Month 5 through Month 6, and Month 10 through Month 12 (for AUC)

• Cabotegravir plasma concentration comparison between patients with severe renal impairment and those without severe renal impairment

  Analysis of CAB LA plasma concentration measures (Ctrough) from participants with severe renal impairment compared to those from historical participants without severe renal impairment.

  Month 2 through Month 12

• Cabotegravir plasma concentration comparison between patients with severe renal impairment and those without severe renal impairment

  Analysis of CAB LA plasma concentration measures (Cmax) from participants with severe renal impairment compared to those from historical participants without severe renal impairment.

  Month 2 through Month 12

• Cabotegravir plasma concentration comparison between patients with severe renal impairment and those without severe renal impairment

  Analysis of CAB LA plasma concentration measures (AUC) from participants with severe renal impairment compared to those from historical participants without severe renal impairment.

  Month 2 through Month 12

• Rilpivirine plasma concentration comparison between patients with severe renal impairment and those without severe renal impairment

  Analysis of RPV LA plasma concentration measures (Ctrough) from participants with severe renal impairment compared to those from historical participants without severe renal impairment.

  Month 2 through Month 12

• Rilpivirine plasma concentration comparison between patients with severe renal impairment and those without severe renal impairment

  Analysis of RPV LA plasma concentration measures (Cmax) from participants with severe renal impairment compared to those from historical participants without severe renal impairment.

  Month 2 through Month 12

• Rilpivirine plasma concentration comparison between patients with severe renal impairment and those without severe renal impairment

  Analysis of RPV LA plasma concentration measures (AUC) from participants with severe renal impairment compared to those from historical participants without severe renal impairment.

  Month 2 through Month 12

Study Arms (1)

HIV + severe renal impairment

EXPERIMENTAL

CAB LA + RPV LA administered to HIV virologically suppressed participants with CKD stage 4/5 (CrCl \< 30 mL/min) with (n = 6) or without (n = 6) hemodialysis receiving CABENUVA monthly for 6 months followed by every 2 months for 6 months.

Drug: CAB + RPV

Interventions

CAB + RPV DRUG

At Day 1 all participants will initiate oral CAB 30 mg + RPV 25 mg once daily for at least 28 days during the Oral Phase. Participants will receive CAB LA 600 mg + RPV LA 900 mg IM injections at month 1 visit followed by CAB LA 400 mg + RPV LA 600 mg IM injections monthly at M2, M3, M4 and M5 visits. Then, starting at month 6 visit, participants will receive CAB LA 600 mg + RPV LA 900 mg IM injections every 2 months at M6, M8, M10 and M12.

HIV + severe renal impairment

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older, at the time of signing the informed consent.
• A female participant is eligible to participate if she is not pregnant as confirmed by negative urine HCG test at screening and at each study visits), not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as:
• Pre-menopausal females with one of the following:
• Documented tubal ligation
• Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion
• Hysterectomy
• Documented Bilateral Oophorectomy
• Postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood test result of simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
• Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (see Appendix 6) from 30 days prior to the first dose of study medication, throughout the study, for at least 14 days after discontinuation of all oral study medications and for at least 52 weeks after discontinuation of CAB LA and RPV LA.
• The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception. The study-sanctioned contraceptive method should be used consistently, in accordance with the approved contraceptive product label, before dosing of study medication and during the study intervention period
• For all participants receiving oral standard of care (SOC) treatment for HIV-1:
• Must be on uninterrupted current regimen (either the initial or second ARV regimen) for at least 6 months prior to Screening.
• Documented evidence of at least two plasma HIV-1 RNA measurements \<50 c/mL in the 12 months prior to Screening: one within the 6 to 12-month window, and one within 6 months prior to Screening
• Plasma HIV-1 RNA \<50 c/mL at Screening

You may not qualify if:

• Screening plasma HIV-1 RNA measurement \> 50 c/mL
• Within 6 months prior to Screening, any plasma HIV-1 RNA measurement \> 200 c/mL
• Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study
• Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification
• Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, 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
• Participants who, in the investigator's judgment, pose a significant suicide risk as assessed via the Columbia Suicidality Severity Rating Scale (C-SSRS). In addition, participant's recent history of mental health, psychiatric history, suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
• Evidence of active Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV DNA as follows:
• Participants positive for HBsAg are excluded:
• Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded, not excluded if HBV DNA is negative or not detected
• Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded
• Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; participants who are anticipated to require HCV treatment within 12 months must be excluded.
• Participants with 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 Week 52 visit. Additional information (where available) on participants with HCV co-infection at screening should include results from any liver biopsy, fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.
• In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility

Sponsors & Collaborators

• Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute): lead

Study Sites (1)

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Conditions

HIV Infections

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician, Physician Investigator, Medical Director Positive Health Clinic

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: November 1, 2022
• Study Start: January 1, 2023
• Primary Completion: April 1, 2025
• Study Completion: May 1, 2025
• Last Updated: June 4, 2025

Record last verified: 2025-06

Locations

US (1)