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

NCT ID: NCT03397121

Last Updated: 2020-10-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

482 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-28

Study Completion Date

2019-09-17

Brief Summary

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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

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Conditions

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Heterozygous Familial Hypercholesterolemia Elevated Cholesterol

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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Inclisiran

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

Group Type EXPERIMENTAL

Inclisiran

Intervention Type DRUG

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Inclisiran

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Saline Solution

Eligibility Criteria

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Inclusion Criteria

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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Medicines Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Frederick J. Raal, MD

Role: PRINCIPAL_INVESTIGATOR

University of Witwatersrand, South Africa

Locations

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Site 90001-005

Mission Viejo, California, United States

Site Status

Site 90001-001

Newport Beach, California, United States

Site Status

Site 90001-015

Stanford, California, United States

Site Status

Site 90001-047

Boca Raton, Florida, United States

Site Status

Site 90001-004

Boston, Massachusetts, United States

Site Status

Site 90001-056

Saint Paul, Minnesota, United States

Site Status

Site 90001-012

Butte, Montana, United States

Site Status

Site 90001-112

Las Vegas, Nevada, United States

Site Status

Site 90001-014

Summit, New Jersey, United States

Site Status

Site 90001-002

Cincinnati, Ohio, United States

Site Status

Site 90011-005

Chicoutimi, Quebec, Canada

Site Status

Site 90011-001

Montreal, Quebec, Canada

Site Status

Site 90011-002

Québec, Quebec, Canada

Site Status

Site 90420-001

Prague, , Czechia

Site Status

Site 90420-006

Prague, , Czechia

Site Status

Site 90420-005

Trutnov, , Czechia

Site Status

Site 90045-001

Aalborg, , Denmark

Site Status

Site 90045-004

Esbjerg, , Denmark

Site Status

Site 90045-003

Herning, , Denmark

Site Status

Site 90045-006

Hvidovre, , Denmark

Site Status

Site 90045-002

Roskilde, , Denmark

Site Status

Site 90045-005

Viborg, , Denmark

Site Status

Site 90031-001

Amersfoort, , Netherlands

Site Status

Site 90031-003

Amsterdam, , Netherlands

Site Status

Site 90031-009

Hoorn, , Netherlands

Site Status

Site 90031-006

Tilburg, , Netherlands

Site Status

Site 90031-005

Utrecht, , Netherlands

Site Status

Site 90027-004

Cape Town, Western Cape, South Africa

Site Status

Site 90027-003

Bloemfontein, , South Africa

Site Status

Site 90027-005

Cape Town, , South Africa

Site Status

Site 90027-001

Cape Town, , South Africa

Site Status

Site 90027-008

Cape Town, , South Africa

Site Status

Site 90027-010

Johannesburg, , South Africa

Site Status

Site 90027-007

Pretoria, , South Africa

Site Status

Site 90027-006

Pretoria, , South Africa

Site Status

Site 90027-009

Witbank, , South Africa

Site Status

Site 90034-003

A Coruña, , Spain

Site Status

Site 90034-005

Barcelona, , Spain

Site Status

Site 90034-004

Córdoba, , Spain

Site Status

Site 90034-006

L'Hospitalet de Llobregat, , Spain

Site Status

Site 90034-001

Reus, , Spain

Site Status

Site 90034-002

Zaragoza, , Spain

Site Status

Site 90046-002

Gothenburg, , Sweden

Site Status

Site 90046-001

Stockholm, , Sweden

Site Status

Site 90046-003

Stockholm, , Sweden

Site Status

Countries

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United States Canada Czechia Denmark Netherlands South Africa Spain Sweden

References

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Dutta S, Shah R, Singhal S, Singh S, Piparva K, Katoch CDS. A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients. Expert Opin Drug Saf. 2024 Feb;23(2):187-198. doi: 10.1080/14740338.2023.2293201. Epub 2023 Dec 19.

Reference Type DERIVED
PMID: 38063346 (View on PubMed)

Raal FJ, Kallend D, Ray KK, Turner T, Koenig W, Wright RS, Wijngaard PLJ, Curcio D, Jaros MJ, Leiter LA, Kastelein JJP; ORION-9 Investigators. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020 Apr 16;382(16):1520-1530. doi: 10.1056/NEJMoa1913805. Epub 2020 Mar 18.

Reference Type DERIVED
PMID: 32197277 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-002472-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MDCO-PCS-17-03

Identifier Type: -

Identifier Source: org_study_id