Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03400800
• Date of registration: 09/01/2018
• Prospective Registration: No
• Primary sponsor: The Medicines Company
• Public title: Inclisiran for Subjects With ASCVD or ASCVD-Risk Equivalents and Elevated Low-density Lipoprotein Cholesterol ORION-11
• Scientific title: A Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Atherosclerotic Cardiovascular Disease (ASCVD) or ACSVD Risk-Equivalents and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)
• Date of first enrolment: November 1, 2017
• Target sample size: 1617
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03400800
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Care Provider).
• Phase: Phase 3

Countries of recruitment

Czechia, Germany, Hungary, Poland, South Africa, Ukraine, United Kingdom

Contacts

• Name: Ray Kausik, MD
• Affiliation: Imperial College of London

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Elevated Cholesterol

Risk Factor, Cardiovascular

ASCVD

Intervention(s)

Drug: Inclisiran Sodium

Drug: Placebo

Primary Outcome(s)

Percentage Change in LDL-C From Baseline to Day 510 [Time Frame: Baseline, Day 510]

Time-adjusted Percent Change in LDL-C Levels From Baseline After Day 90 and up to Day 540 [Time Frame: Baseline, Day 90 to Day 540]

Secondary Outcome(s)

Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510 [Time Frame: Baseline, Day 510]

Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540 [Time Frame: Baseline, Day 90 to Day 540]

Percentage Change in Non-HDL-C From Baseline to Day 510 [Time Frame: Baseline, Day 510]

Percentage Change in Total Cholesterol From Baseline to Day 510 [Time Frame: Baseline, Day 510]

Percentage Change in Apolipoprotein B (ApoB) From Baseline to Day 510 [Time Frame: Baseline, Day 510]

Absolute Change In LDL-C From Baseline To Day 510 [Time Frame: Baseline, Day 510]

Secondary ID(s)

MDCO-PCS-17-08

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/08/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03400800