LDL-C Optimization Using Inclisiran in Patients in Which Drug-Drug Interactions Limit LDL Lowering (SOLVE-LDL-C)

April 8, 2025 updated by: Pam Taub, MD, University of California, San Diego

Study of Optimal LDL-C Value Enhancement With Inclisiran in Patients With Multiple Comorbidities in Which There Are Drug-Drug Interactions Limiting LDL-C Lowering

Drug-drug interactions often limit statin optimization in a population of patients prescribed cytochrome P3A4 inhibitors, which include immunosuppressive agents, protease inhibitors, and antifungals. These patients frequently have autoimmune conditions or rheumatologic disorders that require complex drug regimens and are often on low-dose statin therapy or no statin at all, resulting in suboptimal LDL levels despite increased cardiovascular (CV) risk.

There is an unmet clinical need to improve LDL levels in this vulnerable patient population, which faces increased CV risk due to underlying conditions that also contribute to polypharmacy and multiple drug-drug interactions. This study is a randomized, open-label trial evaluating subcutaneous inclisiran plus standard of care for LDL-C lowering in high-risk primary prevention patients with multiple comorbidities (e.g., Type II diabetes, liver disease, chronic kidney disease, autoimmune disease, solid-organ transplant) who are taking five or more medications in which drug-drug interactions prevent optimization of statin therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an investigator-initiated, single-site, open-label, randomized trial. The investigators will enroll up to 100 high-risk primary prevention patients with at least one comorbidity and an indication for additional lipid control (such as Type II diabetes with A1c ≤ 8.5%, subclinical atherosclerosis, or ASCVD risk of 7.5% or greater). Patients will be randomized 1:1 to the inclisiran arm (n ≥ 50) with standard of care or standard of care alone (n ≥ 50).

The study will consist of five study visits (screening, baseline, 3 months, 9 months, and 12 months). Patients in the inclisiran arm will receive a subcutaneous injection of inclisiran 284 mg for three doses (baseline, 3 months, and 9 months following randomization) as add-on therapy. LDL-C (the primary endpoint) along with other biomarkers will be measured at screening, baseline (inclisiran dose #1), 3 months (inclisiran dose #2), 9 months (inclisiran dose #3), and 12 months (labs only). Patients will also undergo medical history and medication review at each visit. Surveys will be completed at each visit during the study period.

Patients in the control arm (standard of care) will continue with their current lipid-lowering therapy. No adjustments will be made to lipid-lowering therapy during the course of the study. Participants will be aware of the group to which they have been randomized.

The primary objective is to determine the efficacy of inclisiran for LDL-C lowering in high-risk primary prevention patients with multiple comorbidities (e.g., Type II diabetes, autoimmune disease, liver disease, chronic kidney disease, solid-organ transplant) who are taking five or more medications in which drug-drug interactions prevent optimization of statin therapy.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • UC San Diego Altman Clinical and Translational Research Institute
        • Contact:
        • Contact:
        • Contact:
          • Antoinette Birs, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Provision of signed and dated informed consent form.
  • Stated willingness to comply with all study procedures and availability for the duration of the study, including potential randomization to injections.
  • Age >18 and <85 years and able to provide self-consent.
  • Taking five or more prescription drugs at the time of enrollment, of any type.

  • Meets at least one of the following criteria:

    • Elevated 10-year ASCVD risk score ≥7.5% (based on the ACC/AHA ASCVD Risk Estimator Plus tool).
    • Evidence of subclinical atherosclerosis including:

Calcification in any vascular bed, including coronary arteries and aorta. Calcification of cardiac valves. Breast calcification. Carotid plaque that is not hemodynamically significant.

o Type II diabetes on a stable medical regimen with HbA1c <8.5%. Per American Diabetes Association guidelines, patients with Type II diabetes aged 40-75 years should be on a moderate-intensity statin.

Patients with documented partial or complete statin intolerance are eligible for enrollment.

  • On maximally tolerated statin therapy (which can be no statin for patients with documented intolerance) and have suboptimal LDL levels:

    • For patients with Type II diabetes: LDL >70 mg/dL or non-HDL >120 mg/dL.
    • For other patients: LDL >90 mg/dL or non-HDL >120 mg/dL.
  • Willing to adhere to the randomized study regimen, including subcutaneous injection of inclisiran.
  • Agreement to adhere to lifestyle considerations (see Section 5.3) throughout the study duration.

Exclusion Criteria:

  • Prior or current use of inclisiran.
  • Known hypersensitivity or allergy to inclisiran or its components.
  • Active liver disease or unexplained persistent elevations in liver enzymes (ALT or AST >3x upper limit of normal).
  • History of rhabdomyolysis or severe muscle-related statin intolerance.
  • Uncontrolled diabetes (HbA1c >8.5%).
  • Active malignancy requiring systemic therapy.
  • Recent major cardiovascular event (myocardial infarction, stroke, or hospitalization for unstable angina) within the past 3 months.
  • History of organ transplant other than solid-organ transplant.
  • Pregnancy or breastfeeding.
  • Any condition that, in the opinion of the investigator, would make participation unsafe or interfere with study procedures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard of Care, no intervention
Patients will continue the standard of care for lipid lowering as deemed appropriate by their medical team, no changes to lipid lowering therapy are permited during the study.
Active Comparator: Inclisiran Arm
Patients in the intervention arm will be treated with a subcutaneous injection of inclisiran 284mg for three doses (baseline visit, 3 months, then 9 month visit) as add-on therapy to the standard of care for lipid lowering as determined by their medical team.
Drug: Inclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL
The intervention arm will receive subcutaneous injection of inclisiran 284mg at the baseline visit, 3 months and 9 month visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of LDL-Cholesterol
Time Frame: 12 months
Percent Change in LDL-C from baseline to month 12 of treatment with inclisiran as add on to background lipid-lowering therapy that includes maximally tolerated statin.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Atherogenic Lipid Burden
Time Frame: 12 months
Absolute and percent change in LDL particle number, apo B, non-HDL, and small dense LDL, lipoprotein(a), from baseline (Visit 1) to month 12 of treatment with inclisiran
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events
Time Frame: 12 months
Incidence of adverse events occurring during treatment with inclisiran.
12 months
Patient-Reported Experience
Time Frame: 12 months
Patient-reported outcomes and experiences determined by surveys at each visit (the Standardized Treatment Satisfaction Questionnaire with Medication Relationship of the total number of medications on adherence to lipid lowering therapy).
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Diego

Collaborators

Novartis

Investigators

  • Study Director: Michael Wilkinson, MD, University of California, San Diego
  • Study Chair: Eric D Adler, MD, University of California, San Diego
  • Principal Investigator: Pam Taub, MD, University of California, San Diego
  • Study Director: Antoinette Birs, MD, University of California, San Diego

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 3, 2025

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 4, 2025

First Submitted That Met QC Criteria

March 4, 2025

First Posted (Actual)

March 10, 2025

Study Record Updates

Last Update Posted (Actual)

April 11, 2025

Last Update Submitted That Met QC Criteria

April 8, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 810920
  • 315668-00001 (Other Grant/Funding Number: Novartis, Investigator Initiated Study)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) is not expected to be shared due to privacy concerns, institutional policies, and regulatory considerations. However, the Principal Investigator may determine that certain de-identified data may be shared with other researchers on a case-by-case basis, subject to appropriate approvals and data use agreements.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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