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

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

Official Title
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An Open-Label, Single-Arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of ALN-PCSSC in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)

Conditions
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Homozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: ALN-PCSSC
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALN-PCSSC<br>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<br>* ALN-PCSSC is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections.<br>* Other names: PCSK9 synthesis inhibitor;Drug: Standard of Care<br>* Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C |  | Day 1, Day 180 (or Final Visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 60 and to Day 90 in PCSK9 |  | Day 1, Day 60, Day 90 | 
| Absolute Change From Day 1 to Day 60 and to Day 90 in PCSK9 |  | Day 1, Day 60, Day 90 | 
| 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) | 
| 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 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 Triglycerides |  | 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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 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) | 
| 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 | The reported percent change value is the per participant calculated Mean. | 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 Lipoprotein-a |  | Day 1, Day 90, Day 180 (or Final Visit) |