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

NCT03397121 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MDCO-PCS-17-032017-002472-30
• Study Type: interventional
• Target: 482
• Locations: 8 countries
• Sites: 45

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.

Conditions

Heterozygous Familial Hypercholesterolemia; Elevated Cholesterol

Keywords

HeFH; LDL-C; Inclisiran

Outcome Measures

Primary Outcomes (2)

• 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

  Assessments performed at Baseline, Day 90, Day 540, time-adjusted percent change at Day 90 reported

  Baseline, Day 90

Secondary Outcomes (6)

• 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

Study Arms (2)

Inclisiran

EXPERIMENTAL

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

Drug: Inclisiran

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Inclisiran DRUG

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

Inclisiran

Placebo DRUG

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

Also known as: Saline Solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants ≥18 years of age.
• 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.
• Serum LDL-C ≥2.6 millimoles (mmol)/liter (L) (≥100 mg/dL) at screening.
• Fasting triglyceride \<4.52 mmol/L (\<400 mg/dL) at screening.
• Participants on statins should be receiving a maximally tolerated dose.
• Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
• 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.

You may not qualify if:

• New York Heart Association (NYHA) class IV heart failure.
• Uncontrolled cardiac arrhythmia
• Uncontrolled severe hypertension
• Active liver disease
• 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:
• Women \>2 years postmenopausal (defined as 1 year or longer since last menstrual period) AND more than 55 years of age.
• Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
• Women who are surgically sterilized at least 3 months prior to enrollment.
• Males who are unwilling to use an acceptable method of birth control during the entire study period (condom with spermicide).
• Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.
• 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.

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (45)

Site 90001-005

Mission Viejo, California, 92691, United States

Location

Site 90001-001

Newport Beach, California, 92663, United States

Location

Site 90001-015

Stanford, California, 94305, United States

Location

Site 90001-047

Boca Raton, Florida, 33434, United States

Location

Site 90001-004

Boston, Massachusetts, 02114, United States

Location

Site 90001-056

Saint Paul, Minnesota, 55102, United States

Location

Site 90001-012

Butte, Montana, 59701, United States

Location

Site 90001-112

Las Vegas, Nevada, 89119, United States

Location

Site 90001-014

Summit, New Jersey, 07901, United States

Location

Site 90001-002

Cincinnati, Ohio, 45227, United States

Location

Site 90011-005

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Site 90011-001

Montreal, Quebec, H2W 1R7, Canada

Location

Site 90011-002

Québec, Quebec, G1V 4W2, Canada

Location

Site 90420-001

Prague, 140 21, Czechia

Location

Site 90420-006

Prague, 180 00, Czechia

Location

Site 90420-005

Trutnov, 541 01, Czechia

Location

Site 90045-001

Aalborg, DK-9000, Denmark

Location

Site 90045-004

Esbjerg, DK-6700, Denmark

Location

Site 90045-003

Herning, 7400, Denmark

Location

Site 90045-006

Hvidovre, 2650, Denmark

Location

Site 90045-002

Roskilde, DK-4000, Denmark

Location

Site 90045-005

Viborg, DK-8800, Denmark

Location

Site 90031-001

Amersfoort, 3813 TZ, Netherlands

Location

Site 90031-003

Amsterdam, 1105 AZ, Netherlands

Location

Site 90031-009

Hoorn, 1624 NP, Netherlands

Location

Site 90031-006

Tilburg, 5042 AD, Netherlands

Location

Site 90031-005

Utrecht, 3584 CX, Netherlands

Location

Site 90027-004

Cape Town, Western Cape, 7130, South Africa

Location

Site 90027-003

Bloemfontein, 9301, South Africa

Location

Site 90027-005

Cape Town, 7130, South Africa

Location

Site 90027-001

Cape Town, 7500, South Africa

Location

Site 90027-008

Cape Town, 7530, South Africa

Location

Site 90027-010

Johannesburg, 2193, South Africa

Location

Site 90027-007

Pretoria, 0157, South Africa

Location

Site 90027-006

Pretoria, 0184, South Africa

Location

Site 90027-009

Witbank, 1035, South Africa

Location

Site 90034-003

A Coruña, 15006, Spain

Location

Site 90034-005

Barcelona, Spain

Location

Site 90034-004

Córdoba, 14004, Spain

Location

Site 90034-006

L'Hospitalet de Llobregat, 8907, Spain

Location

Site 90034-001

Reus, 43204, Spain

Location

Site 90034-002

Zaragoza, 50009, Spain

Location

Site 90046-002

Gothenburg, SE-41345, Sweden

Location

Site 90046-001

Stockholm, SE-11157, Sweden

Location

Site 90046-003

Stockholm, SE-14186, Sweden

Location

Related Publications (2)

• 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.

  PMID: 38063346 DERIVED

• 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.

  PMID: 32197277 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

ALN-PCS; Saline Solution

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Vice President - Regulatory Operations
• Organization: The Medicines Company

frank.bosley@novartis.com

973-985-0597

Study Officials

• Frederick J. Raal, MD

  University of Witwatersrand, South Africa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 11, 2018
• Study Start: November 28, 2017
• Primary Completion: August 27, 2019
• Study Completion: September 17, 2019
• Last Updated: October 28, 2020
• Results First Posted: October 28, 2020

Record last verified: 2020-10

Locations

NL (5); CZ (3); ZA (9); US (10); SE (3); DK (6); CA (3); ES (6)