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Trial record 1 of 5 for:    Inclisiran
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An Extension Trial of Inclisiran Compared to Evolocumab in Participants With Cardiovascular Disease and High Cholesterol

This study is currently recruiting participants.
Verified September 2017 by The Medicines Company
Sponsor:
ClinicalTrials.gov Identifier:
NCT03060577
First Posted: February 23, 2017
Last Update Posted: September 15, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
The Medicines Company
  Purpose
ORION-3 is a Phase II, open-label, non-randomized, active comparator extension trial to assess the efficacy, safety, and tolerability of long-term dosing of inclisiran and evolocumab given as subcutaneous injections in participants with high cardiovascular risk and elevated low-density lipoprotein cholesterol (LDL-C).

Condition Intervention Phase
Atherosclerotic Cardiovascular Disease Symptomatic Atherosclerosis Type2 Diabetes Familial Hypercholesterolemia Drug: Inclisiran Drug: Evolocumab Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Active Comparator Extension Trial to Assess the Effect of Long Term Dosing of Inclisiran and Evolocumab Given as Subcutaneous Injections in Participants With High Cardiovascular Risk and Elevated LDL-C (ORION-3)

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Percentage Change in LDL-C from Day 1 to Day 210 in the Inclisiran Group [ Time Frame: Day 1, Day 210 ]

Secondary Outcome Measures:
  • Percentage Change of Participants in the Inclisiran Group from Day 1 to Day 210 and to Day 1440 (or Final Visit) in LDL-C [ Time Frame: Day 1, Day 210 and Day 1440 (or Final Visit) ]
  • Change of Participants in the Inclisiran Group from Day 1 to Day 210 and to Day 1440 (or Final Visit) in LDL-C [ Time Frame: Day 1, Day 210 and Day 1440 (or Final Visit) ]
  • Percentage Change of Participants in the Inclisiran Group from Day 1 to Day 210 and to Day 1440 (or Final Visit) in PCSK9 Levels [ Time Frame: Day 1, Day 210 and Day 1440 (or Final Visit) ]
  • Change of Participants in the Inclisiran Group from Day 1 to Day 210 and to Day 1440 (or Final Visit) in PCSK9 Levels [ Time Frame: Day 1, Day 210 and Day 1440 (or Final Visit) ]
  • Percentage Change of Participants in the Inclisiran Group from Day 1 to Day 210 and to Day 1440 (or Final Visit) in Total Cholesterol, Triglycerides, HDL-C, non-HDL-C, VLDL-C, Apo-A1, Apo-B, and Lp(a) [ Time Frame: Day 1, Day 210 and Day 1440 (or Final Visit) ]
  • Change of Participants in the Inclisiran Group from Day 1 to Day 210 and to Day 1440 (or Final Visit) in Total Cholesterol, Triglycerides, HDL-C, non-HDL-C, VLDL-C, Apo-A1, Apo-B, and Lp(a) [ Time Frame: Day 1, Day 210 and Day 1440 (or Final Visit) ]
  • Proportion of Participants in the Inclisiran Group and the Evolocumab Group Who Attain Global Lipid Modification Targets for Their Level of ASCVD Risk [ Time Frame: Day 210 and Day 1440 (or Final Visit) ]
  • Proportion of Participants in the Evolocumab Group Who Attain Global Lipid Modification Targets for Their Level of ASCVD Risk at Day 570 (210 Days After Starting Inclisiran) [ Time Frame: Day 570 ]
  • Proportion of Participants in the Inclisiran Group and the Evolocumab Group with ≥50% LDL-C Reduction [ Time Frame: Day 210 and Day 570 ]
  • Number of Participants in the Inclisiran Group and the Evolocumab Group Reaching on Treatment LDL-C Levels of <25 mg/dL, <50 mg/dL, <70 mg/dL, and <100 mg/dL [ Time Frame: Day 210 and Day 570 ]
  • Time to Lipid Lowering Effect in Participants in the Inclisiran Group and the Evolocumab Group [ Time Frame: Day 1 through Day 1440 ]
  • Change from Day 1 to Day 360 in LDL-C (Beta Quantification) of Participants in the Evolocumab Group [ Time Frame: Day 1, Day 360 ]
  • Change from Day 30 to Day 360 in Participant-Reported Scores Using the Treatment Satisfaction Questionnaire for Medication (TSQM) Questionnaire of Participants in the Inclisiran Group and the Evolocumab Group [ Time Frame: Day 30, Day 360 ]
  • Change from Day 450 to Day 720 in Participant-Reported Scores Using the TSQM Questionnaire of Participants in the Inclisiran Group [ Time Frame: Day 450, Day 720 ]
  • Participant-Reported Adherence to Self-Injectable Evolocumab [ Time Frame: Day 30 through Day 360 ]

Estimated Enrollment: 490
Actual Study Start Date: March 24, 2017
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inclisiran
Participants will receive subcutaneous injections of inclisiran 300 milligrams (mg) on Day 1 and every 180 days thereafter for up to 4 years.
Drug: Inclisiran
Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.
Other Name: ALN-PCSSC
Active Comparator: Evolocumab
Participants will receive self-administered subcutaneous injections of evolocumab 140 mg on Day 1 and every 14 days thereafter until Day 336. Then, the participants will receive subcutaneous injections of inclisiran 300 mg on Day 360 and every 180 days thereafter for up to 4 years.
Drug: Inclisiran
Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.
Other Name: ALN-PCSSC
Drug: Evolocumab
Evolocumab is a fully human monoclonal antibody that inhibits PCSK9.
Other Name: REPATHA

Detailed Description:

ORION-3, an extension of study MDCO-PCS-15-01 (ORION-1) [NCT02597127], is a Phase II, placebo-controlled, double-blind, randomized trial to evaluate the efficacy, safety, and tolerability of inclisiran (ALN-PCSSC) injection(s). All participants who completed ORION-1 (at least up to and including Day 210) and meet the study criteria will be enrolled into this study.

ORION-3 is a long-term extension trial with an active comparator (evolocumab) in participants with atherosclerotic cardiovascular disease (ASCVD) or ASCVD-risk equivalents (diabetes, familial hypercholesterolemia) and elevated LDL-C, despite maximum tolerated dose of LDL-C lowering therapies.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Completion of Study MDCO-PCS-15-01 and no contraindication to receiving inclisiran or evolocumab.
  2. Willing and able to give written and informed consent before initiation of any study related procedures and willing to comply with all required study procedures.
  3. Willing to self-inject.

Exclusion Criteria:

  1. Any uncontrolled or serious disease, or any medical or surgical condition that may either interfere with participation in the clinical study and/or put the participant at significant risk (according to investigator's [or delegate's] judgment).
  2. An underlying known disease or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate), might interfere with interpretation of the clinical study results.
  3. Serious comorbid disease in which the life expectancy of the participant is shorter than the duration of the trial (for example, acute systemic infection, cancer, or other serious illnesses).
  4. Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation greater than 2 times upper limit of normal (ULN); or total bilirubin elevation greater than 1.5 times ULN at study entry visit.
  5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of contraception (for example, oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, intrauterine device) for the entire duration of the study. Exemptions from this criterion are

    • Women >2 years postmenopausal (defined as 1 year or longer since their last menstrual period) AND more than 55 years of age
    • Postmenopausal women (as defined above) and less than 55 years old with a negative pregnancy test within 24 hours of enrollment
    • 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 (that is, condom with spermicide).
  7. Treatment with investigational medicinal products other than inclisiran or devices within 30 days or five half˗lives, whichever is longer.
  8. Planned use of investigational medicinal products other than inclisiran or devices during the course of the study.
  9. Participants with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients
  10. Previous or current treatment (within 90 days of study entry) with monoclonal antibodies directed towards PCSK9.
  11. Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:

    • Inappropriate for this study, including participants who are unable to communicate or to cooperate with the investigator.
    • Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including participants whose cooperation is doubtful due to drug abuse or alcohol dependency).
    • Unlikely to comply with the protocol requirements, instructions, and study-related restrictions (for example, uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study).
    • Involved with, or a relative of, someone directly involved in the conduct of the study.
    • Any known cognitive impairment (for example, Alzheimer's Disease).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03060577


Contacts
Contact: Global Health Science Center 800.288.1183 medical.information@themedco.com
Contact: David Kallend, MBBS +41448098183 david.kallend@themedco.com

  Show 53 Study Locations
Sponsors and Collaborators
The Medicines Company
Investigators
Study Director: David Kallend, MBBS The Medicines Company (Schweiz) GmbH
  More Information

Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT03060577     History of Changes
Other Study ID Numbers: MDCO-PCS-16-01
First Submitted: February 17, 2017
First Posted: February 23, 2017
Last Update Posted: September 15, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Cardiovascular Diseases
Atherosclerosis
Hypercholesterolemia
Hyperlipoproteinemia Type II
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias