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

Phase 3

Completed

• Conditions: Elevated Cholesterol; Heterozygous Familial Hypercholesterolemia
• Interventions: Drug: Placebo; Drug: Inclisiran

• Registration Number: NCT03397121
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-11-28
• Study First Submitted: 2018-01-02
• Study First Submitted QC: 2018-01-05
• Study First Posted: 2018-01-11
• Primary Completion: 2019-08-27
• Study Completion: 2019-09-17
• Results First Submitted: 2020-08-27
• Status Verified: 2020-10
• Results First Submitted QC: 2020-10-06
• Last Update Submitted: 2020-10-06
• Results First Posted: 2020-10-28
• Last Update Posted: 2020-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 482

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo will be administered as SC injections of saline solution on Day 1, Day 90 then every 6 months.
Inclisiran	Inclisiran	Inclisiran sodium 300 milligrams (mg) will be administered as a SC injection on Day 1, Day 90 then every 6 months.

Primary Outcome Measures

Name	Time	Method
Time-adjusted Percent Change in LDL-C From Baseline After Day 90 and up to Day 540	Baseline, Day 90	Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 90 reported
Percent Change in LDL-C From Baseline To Day 510	Baseline, Day 510

Secondary Outcome Measures

Name	Time	Method
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
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	Assessments performed at Baseline, Day 90, Day 540, absolute change at Day 90 reported
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

Trial Locations

Locations (45)

Site 90001-047; 🇺🇸 Boca Raton, Florida, United States

Site 90011-005; 🇨🇦 Chicoutimi, Quebec, Canada

Site 90001-005; 🇺🇸 Mission Viejo, California, United States

Site 90001-001; 🇺🇸 Newport Beach, California, United States

Site 90001-015; 🇺🇸 Stanford, California, United States

Site 90001-014; 🇺🇸 Summit, New Jersey, United States

Site 90031-003; 🇳🇱 Amsterdam, Netherlands

Site 90027-004; 🇿🇦 Cape Town, Western Cape, South Africa

Site 90031-006; 🇳🇱 Tilburg, Netherlands

Site 90034-003; 🇪🇸 A Coruña, Spain

Site 90045-003; 🇩🇰 Herning, Denmark

Site 90045-006; 🇩🇰 Hvidovre, Denmark

Site 90045-002; 🇩🇰 Roskilde, Denmark

Site 90045-005; 🇩🇰 Viborg, Denmark

Site 90001-056; 🇺🇸 Saint Paul, Minnesota, United States

Site 90001-004; 🇺🇸 Boston, Massachusetts, United States

Site 90031-001; 🇳🇱 Amersfoort, Netherlands

Site 90045-001; 🇩🇰 Aalborg, Denmark

Site 90420-006; 🇨🇿 Prague, Czechia

Site 90001-012; 🇺🇸 Butte, Montana, United States

Site 90001-112; 🇺🇸 Las Vegas, Nevada, United States

Site 90001-002; 🇺🇸 Cincinnati, Ohio, United States

Site 90420-005; 🇨🇿 Trutnov, Czechia

Site 90045-004; 🇩🇰 Esbjerg, Denmark

Site 90011-001; 🇨🇦 Montréal, Quebec, Canada

Site 90011-002; 🇨🇦 Quebec City, Quebec, Canada

Site 90420-001; 🇨🇿 Prague, Czechia

Site 90031-009; 🇳🇱 Hoorn, Netherlands

Site 90031-005; 🇳🇱 Utrecht, Netherlands

Site 90034-005; 🇪🇸 Barcelona, Spain

Site 90034-006; 🇪🇸 L'Hospitalet De Llobregat, Spain

Site 90027-007; 🇿🇦 Pretoria, South Africa

Site 90027-009; 🇿🇦 Witbank, South Africa

Site 90027-008; 🇿🇦 Cape Town, South Africa

Site 90027-010; 🇿🇦 Johannesburg, South Africa

Site 90027-003; 🇿🇦 Bloemfontein, South Africa

Site 90046-002; 🇸🇪 Göteborg, Sweden

Site 90046-003; 🇸🇪 Stockholm, Sweden

Site 90034-002; 🇪🇸 Zaragoza, Spain

Site 90027-006; 🇿🇦 Pretoria, South Africa

Site 90027-005; 🇿🇦 Cape Town, South Africa

Site 90034-004; 🇪🇸 Córdoba, Spain

Site 90027-001; 🇿🇦 Cape Town, South Africa

Site 90046-001; 🇸🇪 Stockholm, Sweden

Site 90034-001; 🇪🇸 Reus, Spain