A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH)

NCT02963311 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MDCO-PCS-16-02
• Study Type: interventional
• Target: 9
• Locations: 3 countries
• Sites: 3

Brief Summary

The purpose of this study is to assess the safety, tolerability, and efficacy of ALN-PCSSC in participants with homozygous familial hypercholesterolemia.

Conditions

Homozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (2)

• Percentage Change From Day 1 to Day 90 in LDL-C

  Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented.

  Day 1, Day 90

• Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C

  Day 1, Day 180 (or Final Visit)

Secondary Outcomes (19)

• Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C

  Day 1, Day 90, Day 180 (or Final Visit)

• Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9

  Day 1, Day 60, Day 90

• Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9

  Day 1, Day 60, Day 90

• Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol

  Day 1, Day 90, Day 180 (or Final Visit)

• Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol

  Day 1, Day 90, Day 180 (or Final Visit)

Study Arms (1)

ALN-PCSSC

EXPERIMENTAL

300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by \>70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy.

Drug: ALN-PCSSC; Drug: Standard of Care

Interventions

ALN-PCSSC DRUG

ALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections.

Also known as: PCSK9 synthesis inhibitor

ALN-PCSSC

Standard of Care DRUG

Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.

ALN-PCSSC

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, ≥12 years of age with a diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated low-density lipoprotein cholesterol (LDL-C) concentration \>500 mg/deciliter (dL) \[13 millimoles/liter (mmol/L)\] together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents.
• Stable on a low-fat diet.
• Stable on pre-existing, lipid-lowering therapies (such as statins, cholesterolabsorption inhibitors, bile-acid sequestrants, or combinations thereof) for at least 4 weeks with no planned medication or dose change for the duration of study participation.
• Fasting central lab LDL-C concentration \>130 mg/dL (3.4 mmol/L) and triglyceride concentration \<400 mg/dL (4.5 mmol/L).
• Body weight of 40 kilograms (kg) or greater at screening.

You may not qualify if:

• LDL or plasma apheresis within 8 weeks prior to the screening visit, and no plan to receive it during the study because of the attendant difficulty in maintaining stable concentrations of LDL-C while receiving apheresis.
• Use of mipomersen or lomitapide therapy within 5 months of screening.
• Previous treatment with monoclonal antibodies directed towards PCSK9 within 8 weeks of screening.
• 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 (3)

Research Site 201001

Los Angeles, California, 90001, United States

Location

Research Site 231001

Amsterdam, Netherlands

Location

Research Site 227001

Parktown, Johannesburg, 2193, South Africa

Location

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

ALN-PCS; Standard of Care

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Frank Bosley, Vice-President, Regulatory Operaions
• Organization: The Medicines Company

frank.bosley@themedco.com

9732906016

Study Officials

• Kees Hovingh, MD, PhD

  Department of Vascular Medicine, Academic Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2016
• First Posted: November 15, 2016
• Study Start: December 13, 2016
• Primary Completion: October 8, 2018
• Study Completion: October 8, 2018
• Last Updated: May 18, 2020
• Results First Posted: May 18, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); NL (1); ZA (1)