Study to Identify and Determine Best Implementation Practices for Injectable Cabotegravir+Rilpivirine in the United States (US)

NCT04001803 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 209493
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 9

Brief Summary

Chronic human immunodeficiency virus (HIV) infection in adults continues to be characterized by increased development of resistant virus, increased transmission of resistant virus and issues associated with the long-term toxicity of anti-retroviral therapy (ART), despite advances in development of new ART, which provides extensive insight in management of HIV-infected individuals. Cabotegravir (CAB) is a potent integrase inhibitor (INI) and rilpivirine (RPV) is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI). A two-drug regimen (DR)with CAB plus RPV long acting (LA) product offers many potential advantages over daily oral regimens including better tolerability, improved compliance, adherence, less likely to develop resistance, and overall treatment satisfaction in virologically suppressed subjects. This is a single-arm, open-label, multicenter, short term facilitation study to evaluate the effect of an implementation strategy on the degree of acceptability, appropriateness, feasibility, fidelity and sustainability of clinical practices to deliver the CAB+RPV LA regimen to HIV infected subjects and to also measure subject satisfaction by recording timeliness of visits, length of visit and their education. Approximately 135 subjects will be enrolled in the study and the total duration of the study will be approximately 52-weeks.

Conditions

HIV Infections

Keywords

Antiretroviral therapy, HIV infections, cabotegravir, rilpivirine, long-acting intramuscular injection,

Outcome Measures

Primary Outcomes (10)

• Change From Baseline in the Acceptability of Intervention Measure (AIM) Total Score in Staff Study Participants at Month 4

  AIM is a four item survey that assessed the acceptability of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the AIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 4

• Change From Baseline in AIM Total Score in Staff Study Participants at Month 12

  AIM is a four item survey that assessed the acceptability of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the AIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 12

• Change From Baseline in AIM Total Score in Participants With HIV Infection at Month 4

  AIM is a four item survey that assessed the acceptability of an implementation process. The participants were asked about their impressions of the CAB LA + RPV LA injection treatment for treating HIV on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 4

• Change From Baseline in AIM Total Score in Participants With HIV Infection at Month 12

  AIM is a four item survey that assessed the acceptability of an implementation process. The participants were asked about their impressions of the CAB LA + RPV LA injection treatment for treating HIV on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 12

• Change From Baseline in Intervention Appropriateness Measure (IAM) Score in Staff Study Participants at Month 4

  IAM is a four item survey that assessed the appropriateness of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 4

• Change From Baseline in IAM Score in Staff Study Participants at Month 12

  IAM is a four item survey that assessed the appropriateness of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 12

• Change From Baseline in IAM Score in Participants With HIV Infection at Month 4

  IAM is a four item survey that assessed the appropriateness of an implementation process. The participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 4

• Change From Baseline in IAM Score in Participants With HIV Infection at Month 12

  IAM is a four item survey that assessed the appropriateness of an implementation process. The participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 12

• Change From Baseline in Feasibility of Intervention Measure (FIM) Total Score in Staff Study Participants at Month 4

  FIM is a four item survey that assessed the feasibility of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the FIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The FIM total score ranges from 1 to 5 with 1 indicating the least feasibility and 5 the most feasibility. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 4

• Change From Baseline for FIM Total Score in Staff Study Participants at Month 12

  FIM is a four item survey that assessed the feasibility of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the FIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The FIM total score ranges from 1 to 5 with 1 indicating the least feasibility and 5 the most feasibility. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.

  Baseline and Month 12

Secondary Outcomes (81)

• Number of Staff Study Participants Reported Helpfulness of Toolkit Resources at Month 4

  At Month 4

• Number of Staff Study Participants Reported Helpfulness of Toolkit Resources at Month 12

  At Month 12

• Number of Participants With Change in Barriers to Implementation (BIM) Measure Items Between Baseline and Month 4 Using SSI in Staff Study Participants

  Baseline and Month 4

• Percentage of Participants With Change in BIM Measure Items Between Baseline and Month 12 Using SSI in Staff Study Participants

  Baseline and Month 12

• Number of Participants With HIV Infection Reported Helpfulness of Toolkit Resources at Month 12

  At Month 12

Other Outcomes (3)

• Change From Baseline in Urinalysis Parameters: Urine Albumin to Creatinine Ratio

  Baseline and up to Month 12

• Change From Baseline in Urinalysis Parameters: Urine Protein to Creatinine Ratio

  Baseline and up to Month 12

• Change From Baseline in Urinalysis Parameters: Urine Phosphate

  Baseline and up to Month 12

Study Arms (1)

Subjects with HIV infection

EXPERIMENTAL

HIV-infected subjects receiving CAB LA+RPV LA will be included in this arm.

Drug: CAB LA+RPV LA

Interventions

CAB LA+RPV LA DRUG

Subjects will receive one tablet of CAB 30 milligram(mg) + RPV 25 mg once daily from Day 1 for 1 month. During month 1, subjects will receive 600 mg of CAB LA injection+ 900 mg of RPV LA injection. Following Month 1, subjects will receive 400mg of CAB LA + 600mg of RPV LA at each subsequent injection.

Subjects with HIV infection

Eligibility Criteria

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

You may qualify if:

• Be able to understand and comply with protocol requirements, instructions, and restrictions;
• Understand the long-term commitment to the study and be likely to complete the study as planned;
• Be considered appropriate candidates for participation in an investigative clinical trial with oral and intramuscularly injectable medications (e.g., no active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country, etc.).
• All Participants eligible for enrolment in the study must meet all of the following criteria:
• Aged 18 years or older at the time of signing the informed consent.
• HIV-1 infected and must be on an active highly active antiretroviral therapy (HAART) (2 or 3 drug) 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 treatment failure (HIV-1 RNA \>=200 c/mL).
• Acceptable stable ARV regimens prior to Screening include 2 NRTIs plus:
• INI (either the initial or second Combination antiretroviral therapy (cART) regimen)
• NNRTI (either the initial or second cART regimen)
• Boosted prediction interval (PI) (or atazanavir \[ATV\] unboosted) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability)
• Any suppressed participants on a triple ART regimen for at least 6 months who had their regimen switched to a 2DR of dolutegravir (DTG)/RPV
• \- Documented evidence of at least two plasma HIV-1 RNA measurements \<50 c/mL in the 12 months prior to Screening: at least one within 6 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 defined as:

You may not qualify if:

• Within 6 months prior to Screening, plasma HIV-1 RNA measurement \>=50 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 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 Note: 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.
• Participants who are anticipated to require HCV treatment within 12 months must be excluded. Asymptomatic individuals with chronic hepatitis C virus (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 direct acting antiviral (DAA) drug 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
• Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation Fibrosis 4 Score Formula: (Age x AST) / (Platelets x ( sqr \[ ALT \])

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (9)

GSK Investigational Site

Sacramento, California, 95825, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20017, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32209, United States

Location

GSK Investigational Site

Miami Beach, Florida, 33140, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30309, United States

Location

GSK Investigational Site

Berkley, Michigan, 48072, United States

Location

GSK Investigational Site

Jackson, Mississippi, 39216-4505, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64111, United States

Location

GSK Investigational Site

Dallas, Texas, 75208, United States

Location

Related Publications (2)

• Czarnogorski M, Garris CP, Dalessandro M, D'Amico R, Nwafor T, Williams W, Merrill D, Wang Y, Stassek L, Wohlfeiler MB, Sinclair GI, Mena LA, Thedinger B, Flamm JA, Benson P, Spreen WR. Perspectives of healthcare providers on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings from a Hybrid III Implementation-effectiveness study (CUSTOMIZE). J Int AIDS Soc. 2022 Sep;25(9):e26003. doi: 10.1002/jia2.26003.

  PMID: 36094142 BACKGROUND

• Garris CP, Czarnogorski M, Dalessandro M, D'Amico R, Nwafor T, Williams W, Merrill D, Wang Y, Stassek L, Wohlfeiler MB, Sinclair GI, Mena LA, Thedinger B, Flamm JA, Benson P, Spreen WR. Perspectives of people living with HIV-1 on implementation of long-acting cabotegravir plus rilpivirine in US healthcare settings: results from the CUSTOMIZE hybrid III implementation-effectiveness study. J Int AIDS Soc. 2022 Sep;25(9):e26006. doi: 10.1002/jia2.26006.

  PMID: 36097674 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: ViiV Healthcare

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: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2019
• First Posted: June 28, 2019
• Study Start: July 8, 2019
• Primary Completion: October 5, 2020
• Study Completion: March 18, 2022
• Last Updated: April 14, 2023
• Results First Posted: January 10, 2022

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

US (9)