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

Phase 3Active Not RecruitingNCT05089084

Arrowhead Pharmaceuticals75 enrolled

Overview

The purpose of AROAPOC3-3001 is to evaluate the efficacy and safety of ARO-APOC3 (plozasiran) in adult participants with familial chylomicronemia syndrome (FCS). Participants who have met all eligibility criteria will be randomized to receive 4 doses of plozasiran 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 plozasiran.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Familial Chylomicronemia

Interventions

PlozasiranDRUG

ARO-APOC3 subcutaneous (SC) injection

PlaceboDRUG

sterile normal saline (0.9% NaCl) SC injection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Fasting triglycerides (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

Locations (58)

Outcomes

Primary Outcomes

Percent Change From Baseline at Month 10 in Fasting Triglycerides (TG)

Time frame: Baseline, Month 10

Secondary Outcomes

Percent Change From Baseline in Fasting TG at Month 10 and Month 12 (Averaged)

Time frame: Baseline, Month 10, Month 12

Percent Change From Baseline in Apolipoprotein C-III (APOC3) at Month 10

Time frame: Baseline, Month 10

Percent Change From Baseline in Fasting APOC3 at Month 12

Time frame: Baseline, Month 12

Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Randomized Period)

All adverse events (AEs) and serious adverse events (SAEs) reported by the Investigator during the study that are consistent with an event of acute pancreatitis will be adjudicated by a blinded, independent committee according to the 2013 Atlanta definition meeting 2 of the following 3 criteria: 1. Abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back) 2. Serum lipase activity (or amylase activity) ≥3 times the upper limit of normal (×ULN) 3. Characteristic findings of acute pancreatitis on contrast-enhanced computed tomography (CECT), magnetic resonance imaging (MRI), or transabdominal ultrasonography.

Time frame: From first dose of study drug through Month 12 (Randomized Period)

Percentage of Participants With Positively Adjudicated Events of Acute Pancreatitis (Open-Label Period)

Data from ClinicalTrials.gov

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Clinical Site 1

Boca Raton, Florida, United States

Clinical Site 2

Suwanee, Georgia, United States

Clinical Site 3

Indianapolis, Indiana, United States

Clinical Site 4

Elkridge, Maryland, United States

Clinical Site 5

St Louis, Missouri, United States

Clinical Site 7

New York, New York, United States

Clinical Site 6

New York, New York, United States

Clinical Site 8

Austin, Texas, United States

Clinical Site 9

Norfolk, Virginia, United States

Clinical Site 10

Córdoba, Argentina

...and 48 more locations

Time frame: From first dose of study drug through Month 36 (Open-Label Period)

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Month 10

Time frame: Baseline, Month 10

Percent Change From Baseline in Non-HDL-C at Month 12

Time frame: Baseline, Month 12

Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Month 10

Time frame: Baseline, Month 10

Percent Change From Baseline in HDL-C at Month 12

Time frame: Baseline, Month 12

Percent Change From Baseline in Fasting Triglycerides (TG) at Month 12

Time frame: Baseline, Month 12

Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 10

Time frame: Month 10

Percentage of Participants Achieving Fasting TG of <500, 880, and 1000 mg/dL at Month 12

Time frame: Month 12

Percentage of Participants Achieving ≥40% and ≥70% Reduction From Baseline in Fasting TG at Month 10

Time frame: Baseline, Month 10

Change From Baseline in Fasting TG Over Time

Time frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Percent Change From Baseline in Fasting TG Over Time

Time frame: Baseline, Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

Number of Participants With Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs; Randomized Period)

AE: any untoward medical occurrence which does not necessarily have to have a causal relationship with treatment. Treatment-emergent AEs (TEAEs): AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. SAE: AE that fulfills one or more of the following: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; results in a congenital abnormality or birth defect; is an important medical event that may jeopardize the patient or may require medical intervention to prevent one of the outcomes listed above. Severity was reported as: mild, moderate, severe, life threatening, death.

Time frame: From first dose of study drug through Month 12 (Randomized Period)

Number of Participants With Treatment-Emergent AEs and/or SAEs (Open-Label Period)

Time frame: From first dose of open-label study drug through Month 36 (Open-Label Period)