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

The Medicines Company

Status and phase: Completed; Phase 2

Conditions: Homozygous Familial Hypercholesterolemia

Treatments: Drug: Standard of Care; Drug: ALN-PCSSC

Study type: Interventional

Funder types: Industry

Identifiers

NCT02963311

MDCO-PCS-16-02

Details and patient eligibility

About

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

Enrollment: 9 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

ALN-PCSSC

Experimental group

Description:

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.

Treatment:

Drug: ALN-PCSSC

Drug: Standard of Care