Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia

Phase 2CompletedNCT04720534

Arrowhead Pharmaceuticals229 enrolled

Overview

The purpose of AROAPOC3-2001 is to evaluate the efficacy and safety of ARO-APOC3 in participants with severe hypertriglyceridemia. Participants will receive 2 subcutaneous injections of ARO-APOC3.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

229

Conditions

Severe Hypertriglyceridemia

Interventions

ARO-APOC3DRUG

2 doses of ARO-APOC3 by subcutaneous (sc) injection

PlaceboDRUG

calculated volume to match active treatment by sc injection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Based on medical history, evidence of triglycerides (TG) ≥ 500 mg/dL and ≤ 4000 mg/dL at Screening * Fasting TG ≥ 500 mg/dL at Screening * Willing to follow diet counseling per Investigator judgment based on local standard of care * Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception * Willing to provide written informed consent and to comply with study requirements Exclusion Criteria: * Active pancreatitis within 12 weeks prior to first dose * Any planned bariatric surgery or similar procedures to induce weight loss from consent to end of study * Acute coronary syndrome event within 24 weeks of first dose * Major surgery within 12 weeks of first dose * Planned coronary intervention (e.g., stent placement or heart bypass) or any non-cardiac major surgical procedure throughout the study * Uncontrolled hypertension * Human immunodeficiency virus (HIV) infection, seropositive for Hepatitis B (HBV), seropositive for Hepatitis C (HCV) * Uncontrolled hypothyroidism or hyperthyroidism * Hemorrhagic stroke within 24 weeks of first dose * Malignancy within the last 2 years prior to date of consent requiring systemic treatment (some exceptions apply) Note: additional inclusion/exclusion criteria may apply per protocol

Locations (74)

Outcomes

Primary Outcomes

Percent Change From Baseline at Week 24 in Fasting Triglycerides (TG)

Time frame: Baseline, Week 24

Secondary Outcomes

Percent Change From Baseline Over Time Through Week 48 in Fasting TG

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Percent Change From Baseline at Week 24 in Apolipoprotein (Apo)C-III

Time frame: Baseline, Week 24

Percent Change From Baseline Over Time Through Week 48 in ApoC-III

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Percent Change From Baseline at Week 24 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)

Time frame: Baseline, Week 24

Percent Change From Baseline Over Time Through Week 48 in Fasting Non-High-Density Lipoprotein Cholesterol (Non-HDL-C)

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Percent Change From Baseline at Week 24 in Fasting High-Density Lipoprotein Cholesterol (HDL-C)

Time frame: Baseline, Week 24

Percent Change From Baseline Over Time Through Week 48 in Fasting HDL-C

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Percent Change From Baseline at Week 24 in Fasting Total Apolipoprotein B (ApoB)

Time frame: Baseline, Week 24

Data from ClinicalTrials.gov

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Research Site 2

Beverly Hills, California, United States

Research Site 4

Palm Springs, California, United States

Research Site 5

Boca Raton, Florida, United States

Research Site 6

Fort Lauderdale, Florida, United States

Research Site 10

Miami, Florida, United States

Research Site 9

Miami, Florida, United States

Research Site 11

Miami, Florida, United States

Research Site 8

Miami, Florida, United States

Research Site 12

Miami Springs, Florida, United States

Research Site 14

Port Orange, Florida, United States

...and 64 more locations

Percent Change From Baseline Over Time Through Week 48 in Fasting Total ApoB

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Percent Change From Baseline at Week 24 in Fasting Low-Density Lipoprotein-Cholesterol (LDL-C)

LDL-C analyses used both Martin-Hopkins methodology and ultracentrifugation. The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels.

Time frame: Baseline, Week 24

Percent Change From Baseline Over Time Through Week 48 in Fasting LDL-C

LDL-C analyses used both Martin-Hopkins methodology (MHM) and ultracentrifugation (UC). The Martin-Hopkins formula is a method for calculating LDL-C that improves accuracy by using an adjustable factor for estimating very-low-density lipoprotein (VLDL) cholesterol cholesterol based on triglyceride and non-HDL cholesterol levels.

Time frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 48/early termination (ET)

Change From Baseline in Plasma Concentrations of ARO-APOC3 Over TimeThrough Week 12

Time frame: Day 1: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is a medically important event or reaction. TEAEs are AEs that occur following investigational product (IP) administration or a pre-existing condition exacerbated following IP administration.

Time frame: From first dose of study drug up to Week 48