A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH) (ORION-2)

• Sponsor: The Medicines Company
• Information provided by (Responsible Party): The Medicines Company

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Homozygous Familial Hypercholesterolemia	Drug: ALN-PCSSC; Drug: Standard of Care	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of ALN-PCSSC in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)
• Actual Study Start Date: December 13, 2016
• Actual Primary Completion Date: October 8, 2018
• Actual Study Completion Date: October 8, 2018

Arms and Interventions

Arm

Intervention/treatment

Experimental: ALN-PCSSC; 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; ALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections.; Other Name: PCSK9 synthesis inhibitor; Drug: Standard of Care; Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.

Outcome Measures

Primary Outcome Measures :

1. Percentage Change From Day 1 to Day 90 in LDL-C [ Time Frame: Day 1, Day 90 ]
2. Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C [ Time Frame: Day 1, Day 180 (or Final Visit) ]

Secondary Outcome Measures :

1. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
2. Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9 [ Time Frame: Day 1, Day 60, Day 90 ]
3. Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 [ Time Frame: Day 1, Day 60, Day 90 ]
4. Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol, Triglycerides, HDLC, non-HDL-C, VLDL-C, Apo-A1 Apo-B and Lp(a) [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]
5. Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol, Triglycerides, HDLC, non-HDL-C, VLDL-C, Apo-A1 Apo-B and Lp(a) [ Time Frame: Day 1, Day 90, Day 180 (or Final Visit) ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Contacts and Locations

Locations

United States, California

Research Site 201001

Los Angeles, California, United States, 90001

Netherlands

Research Site 231001

Amsterdam, Netherlands

South Africa

Research Site 227001

Parktown, Johannesburg, South Africa, 2193

Sponsors and Collaborators

The Medicines Company

Investigators

• Principal Investigator: Kees Hovingh, MD, PhD; Department of Vascular Medicine, Academic Medical Center

More Information

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT02963311 History of Changes
• Other Study ID Numbers: MDCO-PCS-16-02
• First Posted: November 15, 2016
• Last Update Posted: December 21, 2018
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipoproteinemia Type II; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hyperlipoproteinemias