Study in Primary Care Evaluating Inclisiran Delivery Implementation + Enhanced Support

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.

The purpose of this study was to evaluate the implementation of inclisiran in a regional primary care setting in the UK

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.

A phase IIIb, multicenter, randomized controlled study to evaluate the implementation, preference, and utility for administration of inclisiran sodium in participants on established lipid lowering medication or, have been recommended lipid lowering therapy by their healthcare provider but are unable to tolerate treatment, with elevated low density lipoprotein cholesterol (LDL-C) in a primary care population. This study was an implementation research study that utilized implementation science methodology and use of the electronic medical record (EMR).

Using implementation science methodology, the study intended to assess the effect of 9 months treatment with inclisiran with/without behavioural support, compared to standard of care + behavioural support, on LDL-C reduction, total lipid profile, assessments of patient and healthcare professional (HCP) satisfaction, health-care resource utilization and healthcare service process evaluation.

The primary focus of this study was implementation and 'transactability' - how to organize, deliver and maintain an innovative treatment for Atherosclerotic Cardiovascular Disease (ASCVD) in a primary care setting in a sustainable way.

Patients taking part in the study were randomised to one of three groups:

• Control + BS: Participants continued to receive their background lipid lowering therapy plus behavioural support. Subjects in treatment group 1 were referred to as the control group in this study
• Inclisiran: Participants continue to receive their background lipid lowering therapy, plus inclisiran for injection (delivered in an injection-only model).
• Inclisiran + BS: Participants continued to receive their background lipid lowering therapy, plus inclisiran for injection, plus behavioural support.

Participants who were randomized to Inclisiran or Inclisiran + BS received one injection of inclisiran on Day 1 and a second injection of inclisiran on Day 90.

Participants in Control + BS and Inclisiran + BS received a monthly telephone call from a health advisor, providing support to enable participants to make positive behaviour changes to reduce their cardiovascular risk.

Inclusion Criteria:

1. Signed informed consent had to be obtained prior to participation in the study.
2. Patients on established lipid lowering medication or, have been recommended lipid lowering therapy by their health care provider but were unable to tolerate treatment.
3. A total cholesterol measurement at screening that was ≥4 mmol/L [approximately 160 mg/dL].
4. Participants on lipid-lowering therapies had to be on a stable dose for ≥30 days before screening with no planned medication or dose change.

Exclusion Criteria:

1. 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 .
2. Current or planned renal dialysis or transplantation.
3. Acute coronary syndrome or stroke less than 4 weeks before the screening visit.
4. Coronary revascularization procedure planned within the next 6 months.
5. 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.
6. Women who are pregnant or breast-feeding.
7. Previous, current or planned treatment with a monoclonal antibody targeting PCSK9, or with a drug known to be contra-indicated with inclisiran.
8. Previous exposure to inclisiran or participation in a randomised study of inclisiran.
9. 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.
10. Participants who planed to move away from the geographical area where the study is being conducted during the study period.
11. A triglyceride measurement at screening that is greater than or equal to 4.52 mmol/L