Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Study Overview
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Brief Summary
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This is a single center, open-label study to evaluate the efficacy of AKCEA-ANGPTL3- LRX for reduction of low density lipoprotein cholesterol (LDL-C) levels in patients with Homozygous Familial Hypercholesterolemia (HoFH).

Official Title
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A Phase 2 Open-Label Study to Assess the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of ISIS 703802 (AKCEA-ANGPTL3-LRx) Administered Subcutaneously to Patients With Homozygous Familial Hypercholesterolemia (HoFH)

Conditions
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Homozygous Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: AKCEA-ANGPTL3-LRX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≤ 35 kg/m2, Genetic confirmation of two mutant alleles at the LDLR, APOB, PCSK9, or LDLRAP1 gene locus OR an untreated LDL-C > 500 mg/dL (13 mmol/L) or treated LDL-C ≥ 300 mg/dL (2.59 mmol/L) together with either cutaneous or tendon xanthoma before age 10 years OR familial medical history of genetically confirmed heterozygous FH in both parents OR untreated elevated LDL-C and TC > 250 mg/dL consistent with the disease, Patients must be on stable LDL-C lowering agents or on regular apheresis Exclusion Criteria: Myocardial infarction, percutaneous transluminal coronary intervention, or coronary artery bypass graft surgery within 12 weeks prior to Screening, or cerebrovascular accident within 24 weeks prior to Screening. Diabetes mellitus if newly diagnosed or if HbA1c ≥ 9.0%

Ages Eligible for Study
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Minimum Age: 18 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: AKCEA-ANGPTL3-LRX Dose 1<br> | Drug: AKCEA-ANGPTL3-LRX<br>* Single open-label cohort<br>* Other names: ISIS 703802;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of low density lipoprotein cholesterol (LDL-C). | Percent change in LDL-C from Baseline to week 14. | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of ISIS 703802 on plasma angiopoietin like 3 (ANGPTL3). | Absolute and percentage change in ANGPTL3 protein from Baseline to Week 14 will be summarized. | 7 and 14 Weeks | 
| Effect of ISIS 703802 on lipid parameters. | Absolute and percentage change from Baseline to Week 14 will be summarized. | 7 and 14 Weeks | 
| Evaluate plasma trough levels of ISIS 703802. | Plasma trough levels of ISIS 703802 during treatment period and those during post-treatment follow up period will be descriptively summarized. | 14 Weeks | 
| The safety of ISIS 703802 by the incidence of treatment-emergent adverse events | The safety of ISIS 703802 will be assessed by determining adverse effects. | 14 Weeks |