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

Overview

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.

Full Title of Study: “A Phase IIIb, Open-label, Hybrid Type III Trial Evaluating Implementation Strategies for Long-acting Cabotegravir Plus Long-acting Rilpivirine Every Two Months in HIV-1 Infected, Virologically Suppressed Adults in Select European Healthcare Settings”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 16, 2022

Interventions

  • Drug: 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.
  • Drug: CAB LA
    • CAB LA 600 mg will be administered as intramuscular (IM) injection.
  • 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.
  • Drug: RPV LA
    • RPV LA 600 mg will be administered as IM injection.
  • Other: 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.

Arms, Groups and Cohorts

  • Experimental: 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.
  • Other: 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).

Clinical Trial Outcome Measures

Primary Measures

  • Change from Baseline in the acceptability of implementation measure (AIM) score in SSP based on Likert scale
    • Time Frame: Baseline and up to 12 months
    • The responses for acceptability will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.
  • Change from Baseline in the implementation appropriateness measure (IAM) score in SSP based on Likert scale
    • Time Frame: Baseline and up to 12 months
    • The responses for appropriateness will be measured on a 5-point Likert scale ranging from 0 to 5 with higher values representing better outcomes.
  • Change from Baseline in the feasibility of implementation measure (FIM) score in SSP based on Likert scale
    • Time Frame: Baseline and up to 12 months
    • The responses for feasibility will be measured on a 5-point Likert scale ranging from 0 to 5 with higher values representing better outcomes.
  • Change from Baseline in theme for acceptability using Semi-structured interviews (SSI) in SSP
    • Time Frame: Baseline and up to 12 months
    • Acceptability will be assessed as part of theme emerging from Exploration, Preparation, Implementation and Sustainment (EPIS) framework guided semi-structured qualitative interview.
  • Change from Baseline in theme for appropriateness using SSI in SSP
    • Time Frame: Baseline and up to 12 months
    • Appropriateness will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.
  • Change from Baseline in theme for feasibility using SSI in SSP
    • Time Frame: Baseline and up to 12 months
    • Feasibility will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.

Secondary Measures

  • Change from Baseline in the Implementation Leadership Scale (ILS) and Implementation climate scale (ICS) in SSP based on Likert scale (Scores on a scale)
    • Time Frame: Baseline and up to 12 months
    • Implementation Leadership and Implementation climate will be assessed through brief self-report measures rated on a 5-point Likert scale ranging from 0 to 5 with higher values representing better outcomes.
  • Change from Baseline in FRAME-Implementation Strategy (IS) outcome in SSP
    • Time Frame: Baseline and up to 12 months
    • The FRAME-IS is a measure that will be completed monthly to provide a precise understanding of modifications, the process of modifying or adapting, and the relationship between different forms of modification and subsequent health and implementation outcomes.
  • Number of SSP participating in CQI calls
    • Time Frame: Up to 12 months
    • Number of SSP participating in CQI calls will be assessed.
  • Change from Baseline in theme for facilitators using SSI in SSP
    • Time Frame: Baseline and up to 12 months
    • Facilitators will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.
  • Change from Baseline in theme for barriers using SSI in SSP
    • Time Frame: Baseline and up to 12 months
    • Barriers will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview
  • Change from Baseline in the use of patient specific toolkit resources to evaluate facilitators in PSP
    • Time Frame: Baseline and up to 12 months
    • Facilitators from the participant’s perspective will be evaluated by the usefulness of the patient specific toolkit resources.
  • Change from Baseline in the use of patient specific toolkit resources to evaluate barriers in PSP
    • Time Frame: Baseline and up to 12 months
    • Barriers from the participant’s perspective will be evaluated by the usefulness of the patient specific toolkit resources.
  • Facilitators to CAB LA + RPV LA in PSP
    • Time Frame: Up to 12 months
    • Facilitators effecting time spent in appointments to receive injections will be assessed.
  • Barriers to CAB LA + RPV LA in PSP
    • Time Frame: Up to 12 months
    • Barriers effecting time spent in appointments to receive injections will be assessed.
  • Length of PSP visit
    • Time Frame: Up to 12 months
    • Length of study visit from arrival until departure from clinic will be evaluated.
  • Change from Baseline in theme for facilitators using SSI in PSP
    • Time Frame: Baseline and up to 12 months
    • Facilitators will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.
  • Change from Baseline in theme for barriers using SSI in PSP
    • Time Frame: Baseline and up to 12 months
    • Barriers will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.
  • Change from Baseline in acceptability of intervention measure (AIM) score, Intervention appropriateness measure (IAM) score and Feasibility of intervention measure (FIM) score in PSP (Scores on a scale)
    • Time Frame: Baseline and up to 12 months
    • The responses for acceptability, appropriateness and feasibility will be measured on a 5-point Likert scale ranging from 0 to 5 with higher values representing better outcomes.
  • Change from Baseline in theme for acceptability using SSI in PSP
    • Time Frame: Baseline and up to 12 months
    • Acceptability will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.
  • Change from Baseline in theme for appropriateness using SSI in PSP
    • Time Frame: Baseline and up to 12 months
    • Appropriateness will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.
  • Change from Baseline in theme for feasibility using SSI in PSP
    • Time Frame: Baseline and up to 12 months
    • Feasibility will be assessed as part of theme emerging from EPIS framework guided semi-structured qualitative interview.
  • Sustainability assessed in SSP using Clinical sustainability assessment tool (CSAT)
    • Time Frame: Up to 12 months
    • The CSAT will evaluate the capability of clinics to maintain processes developed to administer CAB LA+RPV LA injections in routine clinical settings after the conclusion of this study.
  • Percentage of participants in PSP receiving injections within target window
    • Time Frame: Up to 12 months
    • Fidelity will be assessed to CAB LA + RPV LA injection dosing windows.
  • Percentage of participants in PSP with plasma HIV-1 Ribonucleic acid (RNA) less than (<)50 copies per milliliter (c/mL)
    • Time Frame: Up to 12 months
    • Plasma samples will be collected from the participant at specific time points.
  • Percentage of participants in PSP with confirmed virologic failure (CVF)
    • Time Frame: Up to 12 months
    • CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL
  • Number of participants in PSP with treatment-emergent genotypic resistance to CAB
    • Time Frame: Up to 12 months
    • Blood samples will be collected and used for the analysis of genotypic resistance in participants with CVF.
  • Number of participants in PSP with treatment-emergent genotypic resistance to RPV
    • Time Frame: Up to 12 months
    • Blood samples will be collected and used for the analysis of genotypic resistance in participants with CVF.
  • Number of participants in PSP with treatment-emergent phenotypic resistance to CAB
    • Time Frame: Up to 12 months
    • Blood samples will be collected and used for the analysis of phenotypic resistance in participants with CVF.
  • Number of participants in PSP with treatment-emergent phenotypic resistance to RPV
    • Time Frame: Up to 12 months
    • Blood samples will be collected and used for the analysis of phenotypic resistance in participants with CVF.
  • Number of participants in PSP with adverse events (AEs) and serious AEs (SAEs)
    • Time Frame: Up to 12 months
    • All AEs and SAEs will be collected.
  • Percentage of participants in PSP discontinuing treatment due to AEs
    • Time Frame: Up to 12 months
    • Percentage of participants discontinuing treatment due to AEs will be assessed.
  • Number of participants in PSP preferring CAB + RPV LA over daily oral antiretroviral therapy (ART) medication
    • Time Frame: Up to 12 months
    • PSP preference of CAB + RPV LA over daily oral ART medication will be assessed using preference questionnaire.

Participating in This Clinical Trial

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).

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • ViiV Healthcare
  • Collaborator
    • Janssen Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • GSK Clinical Trials, Study Director, ViiV Healthcare
  • Overall Contact(s)
    • US GSK Clinical Trials Call Center, 877-379-3718, GSKClinicalSupportHD@gsk.com

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