SPIRIT: Study in Primary Care Evaluating Inclisiran Delivery Implementation + Enhanced Support

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04807400
• Collaborator: (none)
• Enrollment: 897
• Locations: 17
• Arms: 3
• Anticipated Duration (Months): 18.8
• Patients Per Site: 52.8
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerotic Cardiovascular Disease; Atherosclerotic Cardiovascular Disease Risk Equivelents; Elevated Low Density Lipoprotein Cholesterol	Drug: Inclisiran; Behavioral: Behavioural Support	Phase 3

Detailed Description

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:

1. Continue your current lipid lowering medication, plus a telephone-based lifestyle support programme.

2. Continue your current lipid lowering medication, plus Inclisiran

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 897 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open-Label
• Primary Purpose: Health Services Research
• Official Title: 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.
• Actual Study Start Date: Jul 7, 2021
• Anticipated Primary Completion Date: Jan 30, 2023
• Anticipated Study Completion Date: Jan 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage change in LDL-C from baseline to Day 270 [270 days]

   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.

Secondary Outcome Measures

1. Measurement of patient satisfaction using the validated CSQ-8 (Client Satisfaction Questionnaire) [Day 90]

   Patient satisfaction using CSQ-8 (Client Satisfaction Questionnaire) administered after treatment.

2. Measures of patient activation and empowerment using the validated Patient Activation Measure (PAM) questionnaire [Day 90]

   Patient activation and empowerment using Patient Activation Measure (PAM) questionnaire administered after treatment

3. 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. [Day 90]

   Patient adherence using Patient Activation Measure (PAM) questionnaire administered after treatment

4. Measurement of Feasibility and acceptability of delivery models for inclisiran to patients [Day 270]

   A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery

5. Measurement of Feasibility and acceptability of delivery models for inclisiran to providers (inner setting) [Day 270]

   A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery

6. Measurement of the wider 'transactability' of the proposed delivery models (outer setting) [Day 270]

   A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery

7. Measurement of the service costs of each delivery model [Day 270]

   A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery

8. Measurement of the acceptability and perceived sustainability of patient identification and referral routes [Day 270]

   A process evaluation conducted using the Consolidated Framework for Implementation Research (CFIR) which will explore inclisiran delivery

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Signed informed consent must 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 are unable to tolerate treatment.

3. A total cholesterol measurement at screening that is ≥4 mmol/L [approximately 160 mg/dL].

4. 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:

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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Sale	Cheshire	United Kingdom	M33 4BR
2	Novartis Investigative Site	Altrincham	Manchester	United Kingdom	WA14 1PF
3	Novartis Investigative Site	Davyhulme	Manchester	United Kingdom	M41 7WJ
4	Novartis Investigative Site	Didsbury	Manchester	United Kingdom	M20 6BA
5	Novartis Investigative Site	Northenden	Manchester	United Kingdom	M22 4DH
6	Novartis Investigative Site	Sale	Manchester	United Kingdom	M33 2TB
7	Novartis Investigative Site	Swinton	Manchester	United Kingdom	M27 8HP
8	Novartis Investigative Site	Wythenshawe	Manchester	United Kingdom	M22 0EP
9	Novartis Investigative Site	Wythenshawe	Manchester	United Kingdom	M22 5RX
10	Novartis Investigative Site	Chadderton		United Kingdom	OL9 0LH
11	Novartis Investigative Site	Cheadle Hulme		United Kingdom	SK8 5LL
12	Novartis Investigative Site	Greater Manchester		United Kingdom	M24 4DZ
13	Novartis Investigative Site	Lancashire		United Kingdom	OL6 6EW
14	Novartis Investigative Site	Manchester		United Kingdom	M14 5NP
15	Novartis Investigative Site	Manchester		United Kingdom	M14 6WP
16	Novartis Investigative Site	Manchester		United Kingdom	M20 2RN
17	Novartis Investigative Site	Manchester		United Kingdom	M33 2RH

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04807400
• Other Study ID Numbers: CKJX839A1GB01; 2020-004401-31
• First Posted: Mar 19, 2021
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Atherosclerotic Cardiovascular Disease; Atherosclerotic Cardiovascular Disease Risk Equivalents; Elevated Low Density Lipoprotein Cholesterol; ASCVD; LDL-C
• Additional relevant MeSH terms: Cardiovascular Diseases; Atherosclerosis

Study Results

No Results Posted as of Aug 12, 2022