A Qualitative Hybrid III Implementation Study to Identify and Evaluate Strategies for Successful Implementation of the Cabotegravir + Rilpivirine Long-acting Injectable Regimen in the US
Overview
- Phase
- Phase 3
- Intervention
- CAB LA+RPV LA
- Conditions
- HIV Infections
- Sponsor
- ViiV Healthcare
- Enrollment
- 115
- Locations
- 1
- Primary Endpoint
- Change From Baseline in the Acceptability of Intervention Measure (AIM) Total Score in Staff Study Participants at Month 4
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
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 Exclusionary medical conditions
- •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, except cutaneous Kaposi's sarcoma not requiring systemic therapy, and Cluster of Differentiation (CD4+) counts \<200 cells/microliter 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 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;
Arms & Interventions
Subjects with HIV infection
HIV-infected subjects receiving CAB LA+RPV LA will be included in this arm.
Intervention: CAB LA+RPV LA
Outcomes
Primary Outcomes
Change From Baseline in the Acceptability of Intervention Measure (AIM) Total Score in Staff Study Participants at Month 4
Time Frame: Baseline and 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.
Change From Baseline in IAM Score in Staff Study Participants at Month 12
Time Frame: Baseline and 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.
Change From Baseline in AIM Total Score in Staff Study Participants at Month 12
Time Frame: Baseline and 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.
Change From Baseline in AIM Total Score in Participants With HIV Infection at Month 4
Time Frame: Baseline and 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.
Change From Baseline in IAM Score in Participants With HIV Infection at Month 12
Time Frame: Baseline and 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.
Change From Baseline in IAM Score in Participants With HIV Infection at Month 4
Time Frame: Baseline and 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.
Change From Baseline in AIM Total Score in Participants With HIV Infection at Month 12
Time Frame: Baseline and 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.
Change From Baseline in Intervention Appropriateness Measure (IAM) Score in Staff Study Participants at Month 4
Time Frame: Baseline and 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.
Change From Baseline in Feasibility of Intervention Measure (FIM) Total Score in Staff Study Participants at Month 4
Time Frame: Baseline and 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.
Change From Baseline for FIM Total Score in Staff Study Participants at Month 12
Time Frame: Baseline and 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.
Secondary Outcomes
- Number of Staff Study Participants Using Support Materials/Toolkit at Month 12(At Month 12)
- Number of Staff Study Participants Reported Helpfulness of Toolkit Resources at Month 12(At Month 12)
- Number of Participants With HIV Infection Reported Helpfulness of Toolkit Resources at Month 12(At Month 12)
- Number of Barriers Assessed Among Clinics Using Short-term Facilitation(Up to 6 months)
- Number of Best Practices Assessed Among Clinics Using Short-term Facilitation(Up to 6 months)
- Change From Baseline in Hematology Parameter-Hematocrit From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Hematology Parameter: RBC Count(Up to Month 12)
- Absolute Values of Hematology Parameter: Hemoglobin(Up to Month 12)
- Absolute Values of the Hematology Parameters of Platelet Count, WBC Count, Basophil Count, Eosinophil Count, Lymphocyte Count, Monocyte Count and Neutrophil Count From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Hematology Parameter-RBC Count From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Number of Participants With HIV Reporting Barriers to CAB LA + RPV LA Injection Treatment at Month 12(At Month 12)
- Number of Facilitators Assessed Among Clinics Using Short-term Facilitation(Up to 6 months)
- Number of Staff Study Participants Using Support Materials/Toolkit at Month 4(At Month 4)
- Percentage of Participants With HIV Reporting Helpfulness of the Use of Support Materials/Toolkit at Month 4(At Month 4)
- Number of Staff Study Participants Reported Helpfulness of Toolkit Resources at Month 4(At Month 4)
- 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 Receiving Injections Within Target Window at Month 4(At Month 4)
- Number of Participants Receiving Injections Within Target Window at Month 12(At Month 12)
- Implementation Sustainability Assessed in Staff Study Participants Using Program Sustainability Assessment Tool (PSAT) Scores(At Month 12)
- HIV Treatment Satisfaction Questionnaire Status Version (HIV-TSQs) Scores at Month 1(At Month 1)
- HIV-TSQs Scores at Month 4(At Month 4)
- HIV-TSQs Scores at Month 12(At Month 12)
- Number of Participants With Reported Acceptability of the Amount of Time Spent in the Clinic for Each Injection Visit(At Month 12)
- Number of Participants With the Reported Time Spent in Clinic/Practice for Each Injection Visit(At Month 12)
- Number of Participants With Extent of Knowledge About the CAB + RPV LA Treatment(At Month 12)
- Length of Participant Visit(At Months 1, 5 and 11)
- Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies/Milliliter (c/mL) by Modified Food and Drug Administration (FDA) Snapshot Algorithm(Month 1, Month 2, Month 4, Month 6, Month 8, Month 10 and Month 12)
- Percentage of Participants With Plasma HIV-1 RNA <50 c/mL - Observed Case(Months 1, Month 2, Month 4, Month 6, Month 8, Month 10, Month 12, Month 13, Month 15, Month 16, Month 18, Month 19, Month 21, Month 22, Month 24, Month 25, Month 27, Month 28 and Month 30)
- Percentage of Participants With Confirmed Virologic Failure (CVF)(Up to 30 months)
- Number of Participants With Treatment Emergent Genotypic Resistance to CAB and RPV(Up to 30 months)
- Number of Participants With Treatment Emergent Phenotypic Resistance to CAB and RPV(Up to 30 months)
- Number of Participants With Serious Adverse Events (SAEs) and Common (>=5 Percent [%]) Non-serious Adverse Events (Non-SAEs)(Up to 30 months)
- Percentage of Participants Who Discontinue Treatment or Withdraw From Study Due to AEs Over Time(Up to 30 months)
- Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Relative to Baseline(Up to Month 12)
- Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Relative to Baseline Through End of Study(Up to 30 months)
- Number of Participants With Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline(Up to Month 12)
- Number of Participants With Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline Through End of Study(Up to 30 months)
- Number of Participants With Urinalysis Result of Potential Clinical Importance(Up to Month 12)
- Number of Participants With Urinalysis Result of Potential Clinical Importance Through End of Study(Up to 30 months)
- Number of Participants With Injection Site Reactions (ISRs) Over Time(Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12)
- Number of Participants With Injection Site Reactions (ISRs) Over Time From Month 13 to Month 30(Months 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30)
- Change From Baseline in Hematology Parameters: Platelet Count, White Blood Cell (WBC) Count, Basophil Count, Eosinophil Count, Lymphocyte Count, Monocyte Count and Neutrophil Count(Baseline and up to Month 12)
- Change From Baseline in Hematology Parameter: Red Blood Cell (RBC) Count(Baseline and up to Month 12)
- Change From Baseline in Hematology Parameter: Hemoglobin(Baseline and up to Month 12)
- Change From Baseline in Hematology Parameter: Hematocrit(Baseline and up to Month 12)
- Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume (MCV)(Baseline and up to Month 12)
- Change From Baseline in Hematology Parameters: Platelet Count, White Blood Cell (WBC) Count, Basophil Count, Eosinophil Count, Lymphocyte Count , Monocyte Count and Neutrophil Count From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Hematology Parameter-Red Blood Cell (RBC) Count From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Hematology Parameter-Hemoglobin From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Hematology Parameter-Erythrocytes Mean Corpuscular Volume (MCV) From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Clinical Chemistry Laboratory Parameters: Sodium, Potassium, Carbon-dioxide, Chloride, Glucose, Urea and Phosphate(Up to Month 12)
- Absolute Values of Clinical Laboratory Parameters: Creatinine and Bilirubin(Up to Month 12)
- Absolute Values of Clinical Laboratory Parameters: ALT, ALP, AST, and Creatine Kinase(Up to Month 12)
- Absolute Values of Clinical Laboratory Parameter: Glomerular Filtration Rate (GFR) From Creatinine Adjusted for Body Surface Area (BSA)(Up to Month 12)
- Absolute Values of Clinical Laboratory Parameter: Lipase(Up to Month 12)
- Absolute Values of Clinical Laboratory Parameter: Albumin(Up to Month 12)
- Absolute Values of Clinical Chemistry Laboratory Parameters of Sodium, Potassium, Carbon-dioxide, Chloride, Glucose, Urea and Phosphate From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Clinical Laboratory Parameters: ALT, ALP, AST, and Creatine Kinase From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Absolute Values of the Hematology Parameters: Platelet Count, WBC Count, Basophil Count, Eosinophil Count, Lymphocyte Count, Monocyte Count and Neutrophil Count(Up to Month 12)
- Absolute Values of Hematology Parameter: Hematocrit(Up to Month 12)
- Absolute Values of Hematology Parameter-Hematocrit From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Hematology Parameter-Erythrocytes MCV From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Hematology Parameter: Erythrocytes MCV(Up to Month 12)
- Change From Baseline in Clinical Laboratory Parameter: Glomerular Filtration Rate (GFR) From Creatinine Adjusted for Body Surface Area (BSA)(Baseline and up to Month 12)
- Change From Baseline in Clinical Laboratory Parameter: Lipase(Baseline and up to Month 12)
- Change From Baseline in Clinical Laboratory Parameter: Albumin(Baseline and up to Month 12)
- Change From Baseline in Clinical Chemistry Laboratory Parameters: Sodium, Potassium, Carbon-dioxide, Chloride, Glucose, Urea and Phosphate From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Clinical Laboratory Parameters: ALT, ALP, AST, and Creatine Kinase From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Clinical Laboratory Parameter- Lipase From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Clinical Laboratory Parameter-Albumin From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Hematology Parameter-Hemoglobin From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Clinical Chemistry Laboratory Parameters: Sodium, Potassium, Carbon-dioxide, Chloride, Glucose, Urea and Phosphate(Baseline and up to Month 12)
- Change From Baseline in Clinical Laboratory Parameters: Creatinine and Bilirubin(Baseline and up to Month 12)
- Change From Baseline in Clinical Laboratory Parameters: ALT, ALP, AST, and Creatine Kinase(Baseline and up to Month 12)
- Change From Baseline in Clinical Laboratory Parameter-glomerular Filtration Rate (GFR) From Creatinine Adjusted for Body Surface Area (BSA) From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Clinical Laboratory Parameters: Creatinine and Bilirubin From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Clinical Laboratory Parameter-glomerular Filtration Rate (GFR) From Creatinine Adjusted for Body Surface Area (BSA) From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Change From Baseline in Clinical Laboratory Parameters: Creatinine and Bilirubin From Month 15 to Month 30(Baseline and Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Clinical Laboratory Parameter-Albumin From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)
- Absolute Values of Clinical Laboratory Parameter-Lipase From Month 15 to Month 30(Months 15, 18, 21, 24, 27, 30)