Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol (ORION-11)

The Medicines Company

Status and phase: Completed; Phase 3

Conditions: Elevated Cholesterol; Risk Factor, Cardiovascular; ASCVD

Treatments: Drug: Inclisiran Sodium; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03400800

MDCO-PCS-17-08

Details and patient eligibility

About

This is a Phase III, placebo-controlled, double-blind, randomized study in participants with ASCVD or ASCVD-Risk equivalents 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 an international multicenter study (non-United States).

Enrollment: 1,617 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants may be included if they meet all of the following inclusion criteria prior to randomization:

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. Calculated glomerular filtration rate >30 mL/min by estimated glomerular filtration rate (eGFR) using standardized clinical methodology
6. Participants on statins should be receiving a maximally tolerated dose.
7. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
8. 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.
9. Subjects were willing and able to give informed consent before initiation of any study-related procedures and willing to comply with all required study procedures

Exclusion criteria

Participants will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,617 participants in 2 patient groups, including a placebo group

Inclisiran

Experimental group

Description:

Inclisiran sodium 300 milligrams (mg) (equivalent to 284 mg inclisiran) in 1.5 milliliters (mL) will be administered as a SC injection on Day 1, Day 90, and then every 6 months.

Treatment:

Drug: Inclisiran Sodium

Saline Solution

Placebo Comparator group

Description:

Placebo (1.5 mL) will be administered as a SC injection of saline solution on Day 1, Day 90, and then every 6 months.

Treatment:

Drug: Placebo