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

Homozygous Familial Hypercholesterolemia Clinical Trial

— ORION-2  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02963311
• Other study ID #: MDCO-PCS-16-02
• Status: Completed
• Phase: Phase 2
• Start date: December 13, 2016
• Est. completion date: October 8, 2018

Study information

• Verified date: May 2020
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: October 8, 2018
• Est. primary completion date: October 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Homozygous Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

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

Locations

Country	Name	City	State
Netherlands	Research Site 231001	Amsterdam
South Africa	Research Site 227001	Parktown	Johannesburg
United States	Research Site 201001	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Countries where clinical trial is conducted

United States,  Netherlands,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C		Day 1, Day 180 (or Final Visit)
Secondary	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)
Secondary	Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9		Day 1, Day 60, Day 90
Secondary	Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9		Day 1, Day 60, Day 90
Secondary	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)
Secondary	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)
Secondary	Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B		Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a	The reported percent change value is the per participant calculated Mean.	Day 1, Day 90, Day 180 (or Final Visit)
Secondary	Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a		Day 1, Day 90, Day 180 (or Final Visit)