ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH) (ORION-9)

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: NCT03397121
Recruitment Status : Active, not recruiting
First Posted : January 11, 2018
Last Update Posted : April 9, 2018
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Brief Summary:
This is a Phase III, placebo-controlled, double-blind, randomized study in participants with HeFH and elevated LDL-C to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) injection(s) of inclisiran. The study will be multicenter and international.

Condition or disease Intervention/treatment Phase
Heterozygous Familial Hypercholesterolemia Elevated Cholesterol Drug: Inclisiran Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 482 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C).
Actual Study Start Date : November 28, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Inclisiran
Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months.
Drug: Inclisiran
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.

Placebo Comparator: Placebo
Placebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months.
Drug: Placebo
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).
Other Name: Saline Solution




Primary Outcome Measures :
  1. Percentage Change In LDL-C From Baseline To Day 510 [ Time Frame: Baseline, Day 510 ]
  2. Time-adjusted Percentage Change In LDL-C From Baseline Between Day 90 And Day 540 [ Time Frame: Baseline, Day 90 to Day 540 ]

Secondary Outcome Measures :
  1. Absolute Change in LDL-C from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  2. Time-adjusted Absolute Change in LDL-C from Baseline Between Day 90 and Day 540 [ Time Frame: Baseline, Day 540 ]
  3. Percentage Change in Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  4. Percentage Change in Total Cholesterol from Baseline to Day 510 [ Time Frame: Baseline, Day 510 ]
  5. Percentage Change in Apolipoprotein B (ApoB) from Baseline To Day 510 [ Time Frame: Baseline, Day 510 ]
  6. Percentage Change in Non-high-density Lipoprotein (HDL)-C from Baseline To Day 510 [ Time Frame: Baseline, Day 510 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 HeFH with a diagnosis of HeFH by genetic testing; and/or a documented history of untreated LDL-C of >190 mg/dL, and a family history of familial hypercholesterolemia, elevated cholesterol or early heart disease that may indicate familial hypercholesterolemia.
  3. Serum LDL-C ≥2.6 millimoles (mmol)/liter (L) (≥100 mg/dL) at screening.
  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. Participants on lipid-lowering 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:

Participants will be excluded from the study if any of the following exclusion criteria apply immediately 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) (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 (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.


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): NCT03397121


  Show 46 Study Locations
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: Frederick J. Raal, MD University of Witwatersrand, South Africa

Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT03397121     History of Changes
Other Study ID Numbers: MDCO-PCS-17-03
2017-002472-30 ( EudraCT Number )
First Posted: January 11, 2018    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018

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

Keywords provided by The Medicines Company:
HeFH
LDL-C
Inclisiran

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias