Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol

Phase 3

Completed

• Conditions: ASCVD; Elevated Cholesterol
• Interventions: Drug: Placebo; Drug: Inclisiran Sodium

• Registration Number: NCT03399370
• Lead Sponsor: The Medicines Company

Brief Summary

This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD and elevated LDL-C despite maximum tolerated dose of LDL-C lowering therapies to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) inclisiran injection(s). The study will be a multicenter study in the United States.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-12-21
• Study First Submitted: 2018-01-03
• Study First Submitted QC: 2018-01-08
• Study First Posted: 2018-01-16
• Primary Completion: 2019-09-10
• Study Completion: 2019-09-17
• Results First Submitted: 2020-07-01
• Status Verified: 2020-09
• Results First Submitted QC: 2020-09-08
• Last Update Submitted: 2020-09-08
• Results First Posted: 2020-10-05
• Last Update Posted: 2020-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1561

Inclusion Criteria

1. Male or female participants ≥18 years of age.
2. History of ASCVD (coronary heart disease [CHD], cardiovascular disease [CVD], or peripheral arterial disease [PAD]).
3. Serum LDL-C ≥1.8 millimole (mmol)/liter (L) (≥70 mg/dL).
4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
5. Participants on statins should be receiving a maximally tolerated dose.
6. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
7. Subjects on lipid-lower therapies (such as a statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.

Exclusion Criteria

1. New York Heart Association (NYHA) class IV heart failure.

2. Uncontrolled cardiac arrhythmia

3. Uncontrolled severe hypertension

4. Active liver disease

5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (for example, combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion:

   1. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual period) and more than 55 years of age.
   2. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
   3. Women who are surgically sterilized at least 3 months prior to enrollment.

6. Males who are unwilling to use an acceptable method of birth control during the entire study period (such as condom with spermicide).

7. Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.

8. Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline Solution	Placebo	Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months.
Inclisiran	Inclisiran Sodium	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months.

Primary Outcome Measures

Name	Time	Method
Percentage Change in LDL-C From Baseline to Day 510	Baseline, Day 510
Time-adjusted Percentage Change in LDL-C Levels From Baseline After Day 90 and up to Day 540	Baseline, Day 90 to Day 540	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported

Secondary Outcome Measures

Name	Time	Method
Absolute Change in LDL-C From Baseline to Day 510	Baseline, Day 510
Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540	Baseline, Day 90 to Day 540	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 540 reported
Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510	Baseline, Day 510
Percentage Change in Total Cholesterol From Baseline to Day 510	Baseline, Day 510
Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510	Baseline, Day 510
Percentage Change in Non-HDL-C From Baseline to Day 510	Baseline, Day 510

Trial Locations

Locations (145)

Research Site 10001-015; 🇺🇸 Birmingham, Alabama, United States

Research Site 10001-138; 🇺🇸 Foley, Alabama, United States

Research Site 10001-113; 🇺🇸 Huntsville, Alabama, United States

Research Site 10001-058; 🇺🇸 Mobile, Alabama, United States

Research Site 10001-037; 🇺🇸 Montgomery, Alabama, United States

Research Site 10001-076; 🇺🇸 Saraland, Alabama, United States

Research Site 10001-013; 🇺🇸 Chandler, Arizona, United States

Research Site 10001-077; 🇺🇸 Mesa, Arizona, United States

Research Site 10001-136; 🇺🇸 Phoenix, Arizona, United States

Research Site 10001-051; 🇺🇸 Surprise, Arizona, United States

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