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

Heterozygous Familial Hypercholesterolemia Clinical Trial

— ORION-9  

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03397121
• Other study ID #: MDCO-PCS-17-03
• Secondary ID: 2017-002472-30
• Status: Completed
• Phase: Phase 3
• Start date: November 28, 2017
• Est. completion date: September 17, 2019

Study information

• Verified date: October 2020
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 482
• Est. completion date: September 17, 2019
• Est. primary completion date: August 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Elevated Cholesterol
• Heterozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Drug:
• Inclisiran
Inclisiran is a small interfering ribonucleic acid (RNA) that inhibits PCSK9 synthesis.
• Placebo
Placebo will be supplied as sterile normal saline (0.9% sodium chloride in water for injection).

Locations

Country	Name	City	State
Canada	Site 90011-005	Chicoutimi	Quebec
Canada	Site 90011-001	Montréal	Quebec
Canada	Site 90011-002	Quebec City	Quebec
Czechia	Site 90420-001	Prague
Czechia	Site 90420-006	Prague
Czechia	Site 90420-005	Trutnov
Denmark	Site 90045-001	Aalborg
Denmark	Site 90045-004	Esbjerg
Denmark	Site 90045-003	Herning
Denmark	Site 90045-006	Hvidovre
Denmark	Site 90045-002	Roskilde
Denmark	Site 90045-005	Viborg
Netherlands	Site 90031-001	Amersfoort
Netherlands	Site 90031-003	Amsterdam
Netherlands	Site 90031-009	Hoorn
Netherlands	Site 90031-006	Tilburg
Netherlands	Site 90031-005	Utrecht
South Africa	Site 90027-003	Bloemfontein
South Africa	Site 90027-001	Cape Town
South Africa	Site 90027-004	Cape Town	Western Cape
South Africa	Site 90027-005	Cape Town
South Africa	Site 90027-008	Cape Town
South Africa	Site 90027-010	Johannesburg
South Africa	Site 90027-006	Pretoria
South Africa	Site 90027-007	Pretoria
South Africa	Site 90027-009	Witbank
Spain	Site 90034-003	A Coruña
Spain	Site 90034-005	Barcelona
Spain	Site 90034-004	Córdoba
Spain	Site 90034-006	L'Hospitalet De Llobregat
Spain	Site 90034-001	Reus
Spain	Site 90034-002	Zaragoza
Sweden	Site 90046-002	Göteborg
Sweden	Site 90046-001	Stockholm
Sweden	Site 90046-003	Stockholm
United States	Site 90001-047	Boca Raton	Florida
United States	Site 90001-004	Boston	Massachusetts
United States	Site 90001-012	Butte	Montana
United States	Site 90001-002	Cincinnati	Ohio
United States	Site 90001-112	Las Vegas	Nevada
United States	Site 90001-005	Mission Viejo	California
United States	Site 90001-001	Newport Beach	California
United States	Site 90001-056	Saint Paul	Minnesota
United States	Site 90001-015	Stanford	California
United States	Site 90001-014	Summit	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Denmark,  Netherlands,  South Africa,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in LDL-C From Baseline To Day 510		Baseline, Day 510
Primary	Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 540	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 90 reported	Baseline, Day 90
Secondary	Absolute Change in LDL-C From Baseline to Day 510		Baseline, Day 510
Secondary	Time-adjusted Absolute Change in LDL-C From Baseline After Day 90 and up to Day 540	Assessments performed at Baseline, Day 90, Day 540, absolute change at Day 90 reported	Baseline, Day 90
Secondary	Percentage Change in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) From Baseline to Day 510		Baseline, Day 510
Secondary	Percentage Change in Total Cholesterol From Baseline to Day 510		Baseline, Day 510
Secondary	Percent Change in Apolipoprotein B (Apo-B) From Baseline To Day 510		Baseline, Day 510
Secondary	Percent Change in Non-high-density Lipoprotein (HDL)-C From Baseline To Day 510		Baseline, Day 510