Study in Primary Care Evaluating Inclisiran Delivery Implementation + Enhanced Support

Study Overview
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Brief Summary
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The purpose of the study is to find out if a study treatment called Inclisiran can be given in regional primary care setting (i.e. at a GP surgery in the NHS) in the UK, and to understand how this health care service may be set-up by the NHS. Inclisiran, also known as KJX839, is a medication made to reduce the level of bad cholesterol (LDL-cholesterol) in the blood. Inclisiran works in a way that makes the liver produce less of a substance called 'PCSK9'. PCSK9 reduces the ability of the liver to remove LDL-cholesterol from the blood. By lowering the production of PCSK9, Inclisiran leads to more LDL-cholesterol being removed by the liver from the blood, thereby reducing LDL-cholesterol overall. About 900 patients will participate in this study, at about 20 GP surgeries across the Greater Manchester area within the UK.

Detailed Description
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Using implementation science methodology, the study seeks to assess the effect of 9 months treatment with inclisiran with or without behavioural support, compared to standard of care with behavioural support, on LDL-C reduction, total lipid profile, assessments of patient and healthcare professional (HCP) satisfaction, health-care resource utilisation and healthcare service process evaluation. The primary objective of this study is to demonstrate superiority of inclisiran +/- behavioural support compared to standard of care + behavioural support in a primary care setting, in reducing the percentage change in LDL-C from baseline to Day 270 in adults with elevated LDL-C. Patients taking part in the study, will do so for 9 months. Patients taking part in the study will be randomised to one of three groups: Continue your current lipid lowering medication, plus a telephone-based lifestyle support programme. Continue your current lipid lowering medication, plus Inclisiran Continue your current lipid lowering medication, plus Inclisiran and plus a telephone-based lifestyle support programme. For those patients assigned to group 2 or 3 who will receive Inclisiran, this will be given as an injection from a pre-filled syringe. The patients will be given Inclisiran twice during the study, once at the start of the study on day 1 and a second time 3 months later at day 90. For those patients assigned to group 1 or 3 they will receive a telephone-based lifestyle support programme. Support will be provided to patients through monthly telephone-based support calls, from a health care professional and health advisors. During the calls, support will be offered to ensure patients understand their cardiovascular disease diagnosis and how to implement lifestyle changes that may reduce their risk.

Official Title
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A Phase IIIb, Multicentre, Randomised Controlled Study to Evaluate the Implementation, Preference and Utility for Administration of Inclisiran Sodium in Participants With Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD-risk Equivalents and Elevated Low Density Lipoprotein Cholesterol (LDL-C) Using a Primary Care Models in the NHS.

Conditions
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Atherosclerotic Cardiovascular Disease, Atherosclerotic Cardiovascular Disease Risk Equivelents, Elevated Low Density Lipoprotein Cholesterol

Intervention / Treatment
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* Drug: Inclisiran
* Behavioral: Behavioural Support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Patients on established lipid lowering medication or, have been recommended lipid lowering therapy by their health care provider but are unable to tolerate treatment. A total cholesterol measurement at screening that is ≥4 mmol/L [approximately 160 mg/dL]. Participants on lipid-lowering therapies should be on a stable dose for ≥30 days before screening with no planned medication or dose change. Exclusion Criteria: Medical or surgical history that might limit the individual's ability to take study treatments for the duration of the study and/or put the participant at significant risk . Current or planned renal dialysis or transplantation. Acute coronary syndrome or stroke less than 4 weeks before the screening visit. Coronary revascularization procedure planned within the next 6 months. Women of child-bearing potential, unless they agree to abstinence or, if sexually active, agree to the use of effective methods of contraception during the study. Women who are pregnant or breast-feeding. Previous, current or planned treatment with a monoclonal antibody targeting PCSK9, or with a drug known to be contra-indicated with inclisiran. Previous exposure to inclisiran or participation in a randomised study of inclisiran. Current or previous participation in a clinical study with an unlicensed drug or device within 30 days or five half-lives of the screening visit, whichever is longer. Participants who plan to move away from the geographical area where the study is being conducted during the study period. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Background Therapy + Behavioural Support<br>Participants will continue to receive their background lipid lowering therapy plus behavioural support. | Behavioral: Behavioural Support<br>* Regular telephone based behavioural support programme delivered throughout the study period.<br>|
| Experimental: Backgroud Therapy + Inclisiran<br>Participants will continue to receive their background lipid lowering therapy plus inclisiran for injection. | Drug: Inclisiran<br>* Inclisiran 300 mg 3 monthly (Day 1 and Day 90)<br>|
| Experimental: Background Therapy + Inclisiran + Behavioral Support<br>Participants will continue to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support. | Drug: Inclisiran<br>* Inclisiran 300 mg 3 monthly (Day 1 and Day 90)<br>Behavioral: Behavioural Support<br>* Regular telephone based behavioural support programme delivered throughout the study period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in LDL-C from baseline to Day 270 | Superiority of Inclisiran +/- behavioural support compared to standard of care + behavioural support in a primary care setting, in reducing the percentage change in LDL-C from baseline to Day 270 in adults with elevated LDL-C. | 270 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of patient satisfaction using the validated CSQ-8 (Client Satisfaction Questionnaire) | Patient satisfaction using CSQ-8 (Client Satisfaction Questionnaire) administered after treatment. | Day 90 | 
| Measures of patient activation and empowerment using the validated Patient Activation Measure (PAM) questionnaire | Patient activation and empowerment using Patient Activation Measure (PAM) questionnaire administered after treatment | Day 90 | 
| Measures of adherence to cardiovascular disease self-management using the validated Patient Activation Measure (PAM) questionnaire administered after treatment and using assessment of medication adherence during the study period. | Patient adherence using Patient Activation Measure (PAM) questionnaire administered after treatment | Day 90 | 
| Measurement of Feasibility and acceptability of delivery models for inclisiran to patients | A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery | Day 270 | 
| Measurement of Feasibility and acceptability of delivery models for inclisiran to providers (inner setting) | A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery | Day 270 | 
| Measurement of the wider 'transactability' of the proposed delivery models (outer setting) | A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery | Day 270 | 
| Measurement of the service costs of each delivery model | A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery | Day 270 | 
| Measurement of the acceptability and perceived sustainability of patient identification and referral routes | A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery | Day 270 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerotic Cardiovascular Disease, Atherosclerotic Cardiovascular Disease Risk Equivalents, Elevated Low Density Lipoprotein Cholesterol, ASCVD, LDL-C