A Study Evaluating Implementation Strategies for Cabotegravir (CAB)+ Rilpivirine (RPV) Long-acting (LA) Injectables for Human Immunodeficiency Virus (HIV)-1 Treatment in European Countries

NCT ID: NCT04399551

Last Updated: 2024-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 437 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-28
• Study Completion Date: 2023-03-13

Brief Summary

The overall objective of the CAB LA + RPV LA clinical development program is to develop a highly effective, well-tolerated, two-drug, LA injectable regimen which has the potential to offer improved treatment convenience, compliance and improved quality of life for people living with HIV compared to current standard of care. This interventional study will examine different implementation strategies in different clinic settings across European countries to identify strategies which best meet the needs in each local context and involve both participants receiving study treatment CAB LA + RPV LA (patient study participants [PSP]) as well as the healthcare providers at the investigator site level (staff study participants [SSP]). SSPs consists of 2 groups: standard and enhanced arm.

Conditions

HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants with HIV infection

HIV-infected participants will receive CAB LA + RPV LA regimen for a month of oral lead in (OLI) at Day 1 followed by CAB LA + RPV LA injections at Months 1 and 2 and every 2 months (Q2M) thereafter.

Group Type: EXPERIMENTAL

CAB OLI

Intervention Type: DRUG

CAB will be available as 30 milligrams (mg) tablet. It will be administered as one tablet once daily with food from Day 1 to Month 1.

CAB LA

Intervention Type: DRUG

CAB LA 600 mg will be administered as intramuscular (IM) injection.

RPV OLI

Intervention Type: DRUG

RPV will be available as 25 mg tablet. It will be administered as one tablet once daily with food from Day 1 to Month 1.

RPV LA

Intervention Type: DRUG

RPV LA 900 mg will be administered as IM injection.

Staff study participants (SSP)

Staff study participants will be randomized to receive standard implementation support (Arm-S; through visit(s) with the medication lead in their country, education on the medication, and patient and staff education/support materials) or through enhanced implementation support (Arm-E; through the addition of continuous quality improvement during the study).

Group Type: OTHER

Continuous Quality Improvement (CQI) calls

Intervention Type: OTHER

CQI will be attended by the enhanced arm (Arm-E). The CQI calls will be conducted to identify problems/challenges, generate plans to address the challenges, and identify how to measure the change that results from the plan.

Interventions

CAB OLI

CAB will be available as 30 milligrams (mg) tablet. It will be administered as one tablet once daily with food from Day 1 to Month 1.

Intervention Type: DRUG

CAB LA

CAB LA 600 mg will be administered as intramuscular (IM) injection.

Intervention Type: DRUG

RPV OLI

RPV will be available as 25 mg tablet. It will be administered as one tablet once daily with food from Day 1 to Month 1.

Intervention Type: DRUG

RPV LA

RPV LA 900 mg will be administered as IM injection.

Intervention Type: DRUG

Continuous Quality Improvement (CQI) calls

CQI will be attended by the enhanced arm (Arm-E). The CQI calls will be conducted to identify problems/challenges, generate plans to address the challenges, and identify how to measure the change that results from the plan.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Participants aged 18 years or older at the time of signing the informed consent.
• HIV-1 infected and must be suppressed on a guideline recommended active Highly active antiretroviral therapy (HAART) regimen for at least 6 months prior to screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must not have been done for virologic failure (on treatment HIV-1 RNA more than or equal to [>=]200 c/mL).
• Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: at least one <6 months prior to screening and one 6-12 months prior to screening.
• Plasma HIV-1 RNA <50 c/mL at screening.
• A female participant is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test at screen and at Day 1), not lactating, and at least one of the following conditions applies:

1. Non-reproductive potential is 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 sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. 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.

2. 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 (FRP) from 30 days prior to the first dose of study medication, throughout the study, and for at least 30 days after discontinuation of all oral study medications and for at least 52 weeks after discontinuation of CAB LA and RPV LA.

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants or their legal guardians (and next of kin when locally required), must sign a written informed consent form before any protocol-specified assessments are conducted. Enrolment of participants who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.
• French participants: In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria

• Within 6 months prior to screening, plasma HIV-1 RNA measurement >=50 c/mL.
• During the previous 12 months, any confirmed HIV-1 RNA measurement >=200 c/mL.
• Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during the study.
• Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy, and historical or current Cluster of Differentiation 4 (CD4)+ counts <200 cells per millimeter cube (cells/mm^3) are not exclusionary.
• 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 determined by the investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrolment if the investigator believes the risk of seizure recurrence is low.
• Participants who, in the investigator's judgment, pose a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
• The participant has a tattoo, gluteal implant/ enhancements or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.
• Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (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.
• Participants who are anticipated to require Hepatitis C virus (HCV) treatment within 12 months must be excluded. Asymptomatic individuals with chronic HCV infection will not be excluded; investigators must carefully assess if therapy specific for HCV infection is required. (HCV treatment on study may be permitted, following consultation and approval of the DAA based therapy being considered with the medical monitor).
• Participants with HCV co-infection will be allowed entry into this study if:

1. Liver enzymes meet entry criteria.

2. HCV disease has undergone appropriate work-up, and is not advanced. Additional information (where available) on participants with HCV coinfection 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.

3. In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility:

• Fib-4 score more than (>)3.25 is exclusionary.
• Fib-4 score 1.45-3.25 requires Medical Monitor consultation Fibrosis 4 score formula:

(Age times Aspartate aminotransferase [AST]) / (Platelets times (square [Alanine aminotransferase]{ALT}).

• Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
• History of liver cirrhosis with or without hepatitis viral co-infection.
• Ongoing or clinically relevant pancreatitis.
• Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease.
• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the participant prior to inclusion.
• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (less than or equal to [<=]325 mg per day) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease
• Any evidence of primary resistance based on the presence of any major known Integrase inhibitor (INI) or Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation, except for K103N, by any historical resistance test result.
• ALT >=5 times the upper limit of normal (ULN) or ALT >=3 times ULN and bilirubin >=1.5 times ULN (with >35 percent [%] direct bilirubin).
• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening phase to verify a result.
• Participant has estimated creatinine clearance <50 milliliters per minute (mL/min)/1.73 m^2 via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• 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 Day 1 of this study.
• Treatment with any of the following agents within 28 days of Day 1:

• Radiation therapy.
• Cytotoxic chemotherapeutic agents.
• Tuberculosis therapy except for isoniazid (isonicotinylhydrazid [INH]).
• Anti-coagulation agents.
• Immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons.
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening.
• Use of medications which are associated with Torsade de Pointes must be discussed with the Medical Monitor to determine eligibility.
• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
• A participant with known or suspected active Coronavirus Disease 2019 (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment (World Health Organization [WHO] definitions).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Antwerp, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Orléans, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Vandœuvre-lès-Nancy, , France

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Utrecht, , Netherlands

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Cartagena (Murcia), , Spain

GSK Investigational Site

Marbella, , Spain

GSK Investigational Site

Zaragoza, , Spain

Countries

Belgium; France; Germany; Netherlands; Spain

References

Jonsson-Oldenbuttel C, Ghosn J, van der Valk M, Florence E, Vera F, De Wit S, Rami A, Bonnet F, Hocqueloux L, Hove K, Ait-Khaled M, DeMoor R, Bontempo G, Latham CL, Gutner CA, Iyer S, Gill M, Czarnogorski M, D'Amico R, van Wyk J. Safety and Effectiveness From the Cabotegravir and Rilpivirine Implementation Study in European Locations Study: Phase 3b Hybrid Type III Implementation Study Integrating Cabotegravir + Rilpivirine Long-Acting Into European Clinical Settings. J Acquir Immune Defic Syndr. 2024 Aug 15;96(5):472-480. doi: 10.1097/QAI.0000000000003448. Epub 2024 Jul 9.

Reference Type: DERIVED

PMID: 38985445 (View on PubMed)

Gutner CA, Hocqueloux L, Jonsson-Oldenbuttel C, Vandekerckhove L, van Welzen BJ, Slama L, Crusells-Canales M, Sierra JO, DeMoor R, Scherzer J, Ait-Khaled M, Bontempo G, Gill M, Patel N, D'Amico R, Hove K, Baugh B, Barnes N, Hadi M, Low EL, Anand SB, Hamilton A, Garges HP, Czarnogorski M. Implementation of long-acting cabotegravir and rilpivirine: primary results from the perspective of staff study participants in the Cabotegravir And Rilpivirine Implementation Study in European Locations. J Int AIDS Soc. 2024 Jul;27(7):e26243. doi: 10.1002/jia2.26243.

Reference Type: DERIVED

PMID: 38978405 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

213199

Identifier Type: -

Identifier Source: org_study_id