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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 437
- 试验地点
- 1
- 主要终点
- Change From Baseline in Implementation Appropriateness Measure (IAM-Imp) Score in SSPs at Month 12
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study hence no blinding is required
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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:
- •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 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.
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排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: CAB OLI (Drug)
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.
干预措施: CAB LA (Drug)
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.
干预措施: RPV OLI (Drug)
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.
干预措施: RPV LA (Drug)
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).
干预措施: Continuous Quality Improvement (CQI) calls (Other)
结局指标
主要结局
Change From Baseline in Implementation Appropriateness Measure (IAM-Imp) Score in SSPs at Month 12
时间窗: Baseline (Month 1) and 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.
Number of Participants That Discussed Themes Arising Out of Qualitative Semi-structured Interviews Which Are Coded as Feasibility
时间窗: Up to Month 12
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.
Number of Participants That Discussed Themes Arising Out of Qualitative Semi-structured Interviews Which Are Coded as Appropriateness
时间窗: Up to Month 12
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.
Change From Baseline in Acceptability of Implementation Measure (AIM-Imp) Score in SSP at Month 12
时间窗: Baseline (Month 1) and 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.
Change From Baseline in Feasibility of Implementation Measure (FIM-Imp) Score at Month 12
时间窗: Baseline (Month 1) and 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.
Number of Participants That Discussed Themes Arising Out of Qualitative Semi-structured Interviews Which Are Coded as Acceptability
时间窗: Up to 12 Months
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.
次要结局
- 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 Appropriateness Assessed Via SSIs(Up to 12 Months)
- Change From Baseline in Implementation Leadership Scale (ILS) Score at Month 12(Baseline (Month 1) and Month 12)
- Number of Staff Study Participants That Discussed Facilitators for Appropriateness Assessed Via SSIs(Up to 12 Months)
- Number of Plan, Do, Study, Act (PDSA) Cycles Developed During the Continuous Quality Improvement (CQI) Calls Course(Month 2 to Month 7)
- Number of Participants Who Seek Additional Care From a Dependent to Attend Appointment Assessed Via Questionnaire(Month 12)
- Number of Participants Taking Time Off From Work to Recover From Any Injection Site Reaction Issue Assessed Via Questionnaire(Month 12)
- Number of Participants Rating Convenience of Clinic/Practice's Procedures for Rescheduling Injections Assessed Via Questionnaire(Month 12)
- Number of PSPs That Discussed Facilitators for Appropriateness Assessed Via SSIs(Up to Month 12)
- Number of Staff Study Participants That Discussed Barriers for Acceptability Assessed Via SSIs(Up to 12 Months)
- Number of Participants Rating Acceptability to Come to the Clinic/Practice Every 2 Months for the Injection Visit Assessed Via Questionnaire(Month 12)
- Number of Staff Study Participants That Discussed Barriers for Feasibility Assessed Via SSIs(Up to 12 Months)
- Number of Modifications Reported by SSPs Assessed Via FRAME-IS(Month 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12)
- Number of Participants Rating Acceptability With the Amount of Time Spent in The Clinic/Practice for Each Injection Visit Assessed Via Questionnaire(Month 12)
- Number of Participants Taking Time Off From Work to Attend Appointment Assessed Via Questionnaire(Month 12)
- Number of Participants With Appointment Reminders Received Assessed Via Questionnaire(Month 12)
- Change From Baseline in Intervention Appropriateness Measure (IAM) Score in PSPs at Month 12(Baseline (Month 1) and Month 12)
- Number of Staff Study Participants That Discussed Facilitators for Feasibility Assessed Via SSIs(Up to 12 Months)
- Number of Participants That Endorsed Type of Transportation Used to Attend Appointments(Month 12)
- Number of Participants That Rated Perceived Knowledge About CAB+RPV Injection Treatment Assessed Via Questionnaire(Month 12)
- Number of Participants With Things Tried to Reduce Soreness Following Injections Assessed Via Questionnaire(Month 12)
- Number of PSPs That Discussed Facilitators for Acceptability Assessed Via Semi Structured Interviews (SSIs)(Up to Month 12)
- Number of PSPs That Discussed Facilitators for Feasibility Assessed Via SSIs(Up to Month 12)
- Number of PSPs With Adverse Events (AEs) And Serious AEs (SAEs)(Up to 12 Months)
- Number of PSP With Preference for Therapy Assessed Via Preference Questionnaire(Up to 12 Months)
- Absolute Values of Implementation Climate Scale (ICS) Scores at Month 1 and Month 12(Month 1 and Month 12)
- Number of Participants Spending Average Time in the Clinic/Practice for Each Injection Visit Assessed Via Questionnaire(Up to Month 12)
- Number of Participants Spending Average Time in an Exam Room Waiting for a Nurse (or Other Healthcare Provider) to Get the Injection Administered Assessed Via Questionnaire(Month 12)
- Number of Participants With Time it Took Them to Get to the Clinic Where They Receive HIV Treatment/Check-ups Assessed Via Questionnaire(Month 12)
- Number of Participants Rating Convenience of Clinic/Practice's Procedures for Scheduling Injections Assessed Via Questionnaire(Month 12)
- Number of Participants Who Rated Helpfulness of Appointment Outside of Typical Work Times Assessed Via Questionnaire(Month 12)
- Number of PSPs That Discussed Barriers for Appropriateness Assessed Via SSIs(Up to Month 12)
- Number of Participants With Confirmed Virologic Failure (CVF) Over Time(Month 1, 2, 4, 8, 10 and 12)
- Number of Participants Rating Feelings About Getting CAB+RPV Injection Treatment Assessed Via Questionnaire(Month 12)
- Number of Participants That Rated Agreement in Recommending the CAB+RPV Injections to Others Assessed Via Questionnaire(Month 12)
- Number of PSPs That Discussed Barriers for Acceptability Assessed Via SSIs(Up to Month 12)
- Number of PSPs That Discussed Barriers for Feasibility Assessed Via SSIs(Up to Month 12)
- Change From Baseline in Acceptability of Intervention Measure (AIM) Score in PSPs at Month 12(Baseline (Month 1) and Month 12)
- Change From Baseline in Feasibility of Intervention Measure (FIM) Score in PSPs at Month 12(Baseline (Month 1) and Month 12)
- Associated Person Clinical Sustainability Assessment Tool (APCSAT) Average Domain Score at Month 12(Month 12)
- Percentage of PSP Receiving Injections Within Target Window(Day -7 to Day 7 of Month 2, 4, 6, 8, 10 and 12)
- Percentage of PSPs With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/ml)(Month 1, 2, 4, 8 and 12)
- Number of PSPs Discontinuing Treatment Due to AEs(Up to 12 Months)