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

NCT04399551 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 213199
• Study Type: interventional
• Target: 437
• Locations: 5 countries
• Sites: 18

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

Keywords

Cabotegravir; Rilpivirine; Long-acting injectables; Patient study participants; Staff study participants

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in Acceptability of Implementation Measure (AIM-Imp) Score in SSP at Month 12

  The AIM-Imp was designed to assess the acceptability of an implementation process (i.e., perception among implementation stakeholders that a given treatment, service, practice, or innovation is agreeable, palatable, or satisfactory). The measure consists of four items/statements (1. The implementation support thus far meets my approval 2. The implementation support thus far is appealing to me 3. I like the implementation support I have received 4. I welcome implementation support for the CAB + RPV injection treatment), each with a five-point rating scale (1 = completely disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = completely agree). The mean score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability.

  Baseline (Month 1) and Month 12

• Change From Baseline in Implementation Appropriateness Measure (IAM-Imp) Score in SSPs at Month 12

  The IAM-Imp is designed to assess the appropriateness of an implementation process (i.e., the perceived fit, relevance, or compatibility of the innovation for a given practice setting, provider, or consumer, and the perceived fit of the innovation to address a particular issue or problem). The IAM-Imp is a four-item/statement measure (1. The implementation support thus far seems fitting 2. The implementation support seems suitable for using the CAB + RPV injection treatment 3. The implementation support seems applicable for the CAB + RPV injection treatment 4. The implementation support seems like a good match) with a five-point rating scale (1 = completely disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = completely agree). The mean score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness.

  Baseline (Month 1) and Month 12

• Change From Baseline in Feasibility of Implementation Measure (FIM-Imp) Score at Month 12

  The FIM-Imp was a four-item/statement measure (1. The implementation support seems implementable in our clinic/practice 2. The implementation support seems possible in our clinic/practice 3. The implementation support seems doable in our clinic/practice 4. The implementation support seems easy to use in our clinic/practice) and was measured on a five-point rating scale (1 = completely disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = completely agree). The mean score ranges from 1 to 5 with 1 indicating the least feasibility and 5 the most feasibility.

  Baseline (Month 1) and Month 12

• Number of Participants That Discussed Themes Arising Out of Qualitative Semi-structured Interviews Which Are Coded as Acceptability

  A semi-structured interview guide was designed to support the discussion surrounding experience with the implementation of CAB+RPV LA injection treatment. The interview guide topics were informed by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework and Proctor Outcomes to facilitate discussions on the acceptability from the SSPs' perspective. The results of themes that are integral to successful implementation are presented based on implementation strategies.

  Up to 12 Months

• Number of Participants That Discussed Themes Arising Out of Qualitative Semi-structured Interviews Which Are Coded as Appropriateness

  A semi-structured interview guide was designed to support the discussion surrounding experience with the implementation of CAB+RPV LA injection treatment. The interview guide topics were informed by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework and Proctor Outcomes to facilitate discussions on the appropriateness from the SSPs' perspective. The results of themes that are integral to successful implementation are presented based on implementation strategies.

  Up to Month 12

• Number of Participants That Discussed Themes Arising Out of Qualitative Semi-structured Interviews Which Are Coded as Feasibility

  A semi-structured interview guide was designed to support the discussion surrounding experience with the implementation of CAB+RPV LA injection treatment. The interview guide topics were informed by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework and Proctor Outcomes to facilitate discussions on the feasibility from the SSPs' perspective. The results of themes that are integral to successful implementation are presented based on implementation strategies.

  Up to Month 12

Secondary Outcomes (43)

• Number of Staff Study Participants That Discussed Facilitators for Acceptability Assessed Via Semi Structured Interviews (SSIs)

  Up to 12 Months

• Number of Staff Study Participants That Discussed Barriers for Acceptability Assessed Via SSIs

  Up to 12 Months

• Number of Staff Study Participants That Discussed Facilitators for Appropriateness Assessed Via SSIs

  Up to 12 Months

• Number of Staff Study Participants That Discussed Barriers for Appropriateness Assessed Via SSIs

  Up to 12 Months

• Number of Staff Study Participants That Discussed Facilitators for Feasibility Assessed Via SSIs

  Up to 12 Months

Study Arms (2)

Participants with HIV infection

EXPERIMENTAL

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.

Drug: CAB OLI; Drug: CAB LA; Drug: RPV OLI; Drug: RPV LA

Staff study participants (SSP)

OTHER

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).

Other: Continuous Quality Improvement (CQI) calls

Interventions

CAB OLI 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.

Participants with HIV infection

CAB LA DRUG

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

Participants with HIV infection

RPV OLI 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.

Participants with HIV infection

RPV LA DRUG

RPV LA 900 mg will be administered as IM injection.

Participants with HIV infection

Continuous Quality Improvement (CQI) calls 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.

Staff study participants (SSP)

Eligibility Criteria

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

You may qualify if:

• 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:
• 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.
• 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.

You may not qualify if:

• 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 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:
• Liver enzymes meet entry criteria.
• 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.
• 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

• ViiV Healthcare: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (18)

GSK Investigational Site

Antwerp, 2000, Belgium

Location

GSK Investigational Site

Brussels, 1000, Belgium

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Bordeaux, 33075, France

Location

GSK Investigational Site

Orléans, 45067, France

Location

GSK Investigational Site

Paris, 75004, France

Location

GSK Investigational Site

Paris, 75010, France

Location

GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Vandœuvre-lès-Nancy, 54511, France

Location

GSK Investigational Site

Munich, Bavaria, 80337, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

GSK Investigational Site

Utrecht, 3584 CX, Netherlands

Location

GSK Investigational Site

Alicante, 03010, Spain

Location

GSK Investigational Site

Cartagena (Murcia), 30202, Spain

Location

GSK Investigational Site

Marbella, 29600, Spain

Location

GSK Investigational Site

Zaragoza, 50009, Spain

Location

Related Publications (2)

• 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.

  PMID: 38985445 DERIVED

• 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.

  PMID: 38978405 DERIVED

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study hence no blinding is required
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2020
• First Posted: May 22, 2020
• Study Start: September 28, 2020
• Primary Completion: March 7, 2022
• Study Completion: March 13, 2023
• Last Updated: April 5, 2024
• Results First Posted: May 19, 2023

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

BE (4); ES (4); NL (2); DE (2); FR (6)