Clinical trial NCT02963311: A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Homozygous Familial Hypercholesterolemia
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2016-11-15
Enrollment: 9
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Percentage Change From Day 1 to Day 90 in LDL-C
timeFrame: Day 1, Day 90
measure: Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C
timeFrame: Day 1, Day 180 (or Final Visit)
Secondary outcomes:
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in LDL-C
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 60 and to Day 90 in PCSK9
timeFrame: Day 1, Day 60, Day 90
measure: Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9
timeFrame: Day 1, Day 60, Day 90
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Total Cholesterol
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Triglycerides
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in HDL-C
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Non-HDL-C
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in VLDL-C
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein A1
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Apolipoprotein B
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Percentage Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
measure: Absolute Change From Day 1 to Day 90 and to Day 180 (or Final Visit) in Lipoprotein-a
timeFrame: Day 1, Day 90, Day 180 (or Final Visit)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site 201001
state: California
city: Amsterdam
country: Netherlands
facility: Research Site 231001
city: Parktown
country: South Africa
facility: Research Site 227001
state: Johannesburg
Study officials:
affiliation: Department of Vascular Medicine, Academic Medical Center
name: Kees Hovingh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: