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

Phase 2

Completed

Conditions: Homozygous Familial Hypercholesterolemia

Interventions: Drug: ALN-PCSSC
Drug: Standard of Care

Registration Number: NCT02963311

Lead Sponsor: The Medicines Company

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 9

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ALN-PCSSC	Standard of Care	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.
ALN-PCSSC	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.

Primary Outcome Measures

Name	Time	Method
Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C	Day 1, Day 180 (or Final Visit)
Percentage Change From Day 1 to Day 90 in LDL-C	Day 1, Day 90	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.

Secondary Outcome Measures

Name	Time	Method
Absolute 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 90 and to Day 180 (or Final Visit) in Triglycerides	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 90 and to Day 180 (or Final Visit) in Total Cholesterol	Day 1, Day 90, Day 180 (or Final Visit)
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)
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)
Percentage 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)	The reported percent change value is the per participant calculated Mean.
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)
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)
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)
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)
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)
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)
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 90 and to Day 180 (or Final Visit) in Total Cholesterol	Day 1, Day 90, Day 180 (or Final Visit)
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)
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)
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)
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)

Trial Locations

Locations (3): Research Site 201001
🇺🇸
Los Angeles, California, United States
Research Site 231001
🇳🇱
Amsterdam, Netherlands
Research Site 227001
🇿🇦
Parktown, Johannesburg, South Africa
Research Site 201001
🇺🇸Los Angeles, California, United States