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

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).

Sponsors

Lead Sponsor: The Medicines Company

Source 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.

Overall Status Completed
Start Date November 28, 2017
Completion Date September 17, 2019
Primary Completion Date August 27, 2019
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Percent Change in LDL-C From Baseline To Day 510 Baseline, Day 510
Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 540 Baseline, Day 90
Secondary Outcome
Measure Time Frame
Absolute Change in LDL-C From Baseline to Day 510 Baseline, Day 510
Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540 Baseline, Day 90
Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510 Baseline, Day 510
Percentage Change in Total Cholesterol From Baseline to Day 510 Baseline, Day 510
Percent Change in Apolipoprotein B (Apo-B) From Baseline To Day 510 Baseline, Day 510
Percent Change in Non-high-density Lipoprotein (HDL)-C From Baseline To Day 510 Baseline, Day 510
Enrollment 482
Condition
Intervention

Intervention Type: Drug

Intervention Name: Inclisiran

Description: Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.

Arm Group Label: Inclisiran

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Arm Group Label: Placebo

Other Name: Saline Solution

Eligibility

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Frederick J. Raal, MD Principal Investigator University of Witwatersrand, South Africa
Location
Facility:
Site 90001-005 | Mission Viejo, California, 92691, United States
Site 90001-001 | Newport Beach, California, 92663, United States
Site 90001-015 | Stanford, California, 94305, United States
Site 90001-047 | Boca Raton, Florida, 33434, United States
Site 90001-004 | Boston, Massachusetts, 02114, United States
Site 90001-056 | Saint Paul, Minnesota, 55102, United States
Site 90001-012 | Butte, Montana, 59701, United States
Site 90001-112 | Las Vegas, Nevada, 89119, United States
Site 90001-014 | Summit, New Jersey, 07901, United States
Site 90001-002 | Cincinnati, Ohio, 45227, United States
Site 90011-005 | Chicoutimi, Quebec, G7H 7K9, Canada
Site 90011-001 | Montréal, Quebec, H2W 1R7, Canada
Site 90011-002 | Quebec City, Quebec, G1V 4W2, Canada
Site 90420-001 | Prague, 140 21, Czechia
Site 90420-006 | Prague, 180 00, Czechia
Site 90420-005 | Trutnov, 541 01, Czechia
Site 90045-001 | Aalborg, DK-9000, Denmark
Site 90045-004 | Esbjerg, DK-6700, Denmark
Site 90045-003 | Herning, 7400, Denmark
Site 90045-006 | Hvidovre, 2650, Denmark
Site 90045-002 | Roskilde, DK-4000, Denmark
Site 90045-005 | Viborg, DK-8800, Denmark
Site 90031-001 | Amersfoort, 3813 TZ, Netherlands
Site 90031-003 | Amsterdam, 1105 AZ, Netherlands
Site 90031-009 | Hoorn, 1624 NP, Netherlands
Site 90031-006 | Tilburg, 5042 AD, Netherlands
Site 90031-005 | Utrecht, 3584 CX, Netherlands
Site 90027-004 | Cape Town, Western Cape, 7130, South Africa
Site 90027-003 | Bloemfontein, 9301, South Africa
Site 90027-005 | Cape Town, 7130, South Africa
Site 90027-001 | Cape Town, 7500, South Africa
Site 90027-008 | Cape Town, 7530, South Africa
Site 90027-010 | Johannesburg, 2193, South Africa
Site 90027-007 | Pretoria, 0157, South Africa
Site 90027-006 | Pretoria, 0184, South Africa
Site 90027-009 | Witbank, 1035, South Africa
Site 90034-003 | A Coruña, 15006, Spain
Site 90034-005 | Barcelona, Spain
Site 90034-004 | Córdoba, 14004, Spain
Site 90034-006 | L'Hospitalet De Llobregat, 8907, Spain
Site 90034-001 | Reus, 43204, Spain
Site 90034-002 | Zaragoza, 50009, Spain
Site 90046-002 | Göteborg, SE-41345, Sweden
Site 90046-001 | Stockholm, SE-11157, Sweden
Site 90046-003 | Stockholm, SE-14186, Sweden
Location Countries

Canada

Czechia

Denmark

Netherlands

South Africa

Spain

Sweden

United States

Verification Date

October 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Inclisiran

Type: Experimental

Description: Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months.

Label: Placebo

Type: Placebo Comparator

Description: Placebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months.

Acronym ORION-9
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Care Provider)

Source: ClinicalTrials.gov