Study of ARO-APOC3 in Adults With Familial Chylomicronemia Syndrome (FCS)

Study Overview
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Brief Summary
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The purpose or AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 in adult participants with familial chylomicronemia syndrome (FCS). Participants who have met all eligibility criteria will be randomized to receive 4 doses of ARO-APOC3 or matching placebo administered subcutaneously. Participants who complete the randomized period will continue in a 2-year open-label extension period where all participants will receive ARO-APOC3.

Official Title
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A Phase 3 Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Familial Chylomicronemia Syndrome

Conditions
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Familial Chylomicronemia

Intervention / Treatment
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* Drug: ARO-APOC3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fasting TG ≥ 10 mmol/L (≥ 880 mg/dL) at screening refractory to standard lipid lowering therapy Diagnosis of FCS Willing to follow dietary counseling as per investigator judgement based on local standard of care Participants of childbearing potential (males & females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm during the study and for at least 24 weeks following the last dose of study medication Women of childbearing potential must have a negative pregnancy test at Screening and cannot be breastfeeding Women of childbearing potential on hormonal contraceptives must be stable on the medication for ≥ 2 menstrual cycles prior to Day 1 Exclusion Criteria: Current use or use within the last 365 Days from Day 1 of any hepatocyte-targeted siRNA or antisense oligonucleotide molecule Diabetes mellitus newly diagnosed within 12 weeks of Screening or where HbA1c ≥ 9.0% at Screening Active pancreatitis within 12 weeks before Day 1 History of acute coronary syndrome event within 24 weeks of Day 1 History of major surgery within 12 weeks of Day 1 Uncontrolled hypertension On treatment with human immunodeficiency virus (HIV) antiretroviral therapy Seropositive for hepatitis B virus (HBV) or hepatitis C virus (HCV) New York Heart Association (NYHA) Clas II, III, or IV heart failure Note: Additional Inclusion/Exclusion criteria may apply per protocol

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARO-APOC3<br>4 doses of ARO-APOC3 by subcutaneous (sc) injection (randomized period) 8 doses of ARO-APOC3 by sc injection (open-label period) | Drug: ARO-APOC3<br>* ARO-APOC3 injection<br>|
| Placebo Comparator: Placebo<br>calculated volume to match active treatment by sc injection (randomized period) | Drug: Placebo<br>* sterile normal saline (0.9% NaCl)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Fasting Triglycerides (TG) at Month 10 |  | Baseline, Month 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Fasting TG at Month 10 and Month 12 (Averaged) |  | Baseline, Month 10, Month 12 | 
| Percent Change from Baseline in Apolipoprotein C-III (APOC3) at Month 10 |  | Baseline, Month 10 | 
| Percent Change from Baseline in Fasting APOC3 at Month 12 |  | Baseline, Month 12 | 
| Percent Change from Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10 |  | Baseline, Month 10 | 
| Percent Change from Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10 |  | Baseline, Month 10 | 
| Percent Change from Baseline in Fasting TG at Month 12 |  | Baseline, Month 12 | 
| Percent Change from Baseline in Fasting Non-HDL-C at Month 12 |  | Baseline, Month 12 | 
| Percent Change from Baseline in Fasting HDL-C at Month 12 |  | Baseline, Month 12 | 
| Proportion of Patients Achieving TG of < 500 mg/dL at Month 10 |  | Month 10 | 
| Proportion of Patients Achieving TG of < 500 mg/dL at Month 12 |  | Month 12 | 
| Change from Baseline in Fasting TG Over Time |  | Baseline, up through Month 12 | 
| Percent Change from Baseline in Fasting TG Over Time |  | Baseline, up through Month 12 | 
| Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs) |  | From first dose of study drug through Month 12 (Randomized Period) and through Month 36 (Open-label Period) | 
| Number of Participants with Positively Adjudicated Events of Acute Pancreatitis |  | From first dose of study drug through Month 12 (Randomized Period) and through Month 36 (Open-label Period) |