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Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol (ORION-10)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03399370
Recruitment Status : Active, not recruiting
First Posted : January 16, 2018
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Tracking Information
First Submitted Date  ICMJE January 3, 2018
First Posted Date  ICMJE January 16, 2018
Last Update Posted Date April 17, 2019
Actual Study Start Date  ICMJE December 21, 2017
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Percentage Change in LDL-C from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  • Time-adjusted Percentage Change in LDL-C Levels from Baseline after Day 90 and up to Day 540 [ Time Frame: Baseline, Day 90, Day 540 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Percentage Change in LDL-C from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  • Time-adjusted Percentage Change in LDL-C Levels from Baseline between Day 90 and Day 540 [ Time Frame: Baseline, Day 90, Day 540 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Absolute Change in LDL-C 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, Day 540 ]
  • Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) 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 ]
  • Percentage Change in Non-HDL-C from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Absolute Change in LDL-C from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  • Time-adjusted Absolute Change in LDL-C from Baseline between Day 90 and Day 540 [ Time Frame: Baseline, Day 90, Day 540 ]
  • Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) 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 ]
  • Percentage Change in Non-HDL-C from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol
Official Title  ICMJE 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) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE
  • ASCVD
  • Elevated Cholesterol
Intervention  ICMJE
  • Drug: Inclisiran Sodium
    Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
  • Drug: Placebo
    Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
    Other Name: Saline Solution
Study Arms  ICMJE
  • Experimental: Inclisiran
    Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90, then every 6 months.
    Intervention: Drug: Inclisiran Sodium
  • Placebo Comparator: Saline Solution
    Placebo will be administered as a SC injection of saline solution on Day 1, Day 90, then every 6 months.
    Intervention: Drug: Placebo
Publications * Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, Bisch JA, Richardson T, Jaros M, Wijngaard PLJ, Kastelein JJP; ORION-10 and ORION-11 Investigators. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa1912387. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 20, 2018)
1561
Original Estimated Enrollment  ICMJE
 (submitted: January 8, 2018)
1500
Estimated Study Completion Date  ICMJE December 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03399370
Other Study ID Numbers  ICMJE MDCO-PCS-17-04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The Medicines Company
Study Sponsor  ICMJE The Medicines Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Scott Wright, MD Mayo Clinic
PRS Account The Medicines Company
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP