Study of ARO-ANG3 in Adults With Mixed Dyslipidemia

Arrowhead Pharmaceuticals204 enrolled

Overview

The purpose of AROANG3-2001 is to evaluate the efficacy and safety of ARO-ANG3 in participants with mixed dyslipidemia. Participants will initially receive 2 subcutaneous injections of ARO-ANG3 or placebo. Participants who complete the double-blind treatment period may opt to continue in an open-label extension during which they will receive up to 8 doses of ARO-ANG3.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

204

Conditions

Mixed Dyslipidemia

Interventions

ARO-ANG3DRUG

ARO-ANG3 Injection

PlaceboDRUG

Sterile Normal Saline (0.9% NaCl)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Based on medical history, evidence of triglycerides (TG) ≥ 150 mg/dL but ≤ 499 mg/dL * Fasting levels at Screening of LDL-C ≥ 70 mg/dL OR non-HDL-C ≥ 100 mg/dL after at least 4 weeks of stable diet and stable optimal statin therapy * Mean fasting TG ≥ 150 mg/dL and ≤ 499 mg/dL during Screening collected at two separate and consecutive visits and at least 7 days apart and not more than 17 days apart * Willing to follow diet counseling and maintain a stable diet per Investigator judgment based on local standard of care * Participants of childbearing potential must agree to use highly-effective contraception during the study and for at least 24 weeks from last dose of study medication * Women of childbearing potential must have a negative pregnancy test 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 * Men must not donate sperm during the study and for at least 24 weeks following the last dose of study medication * Able and willing to provide written informed consent and to comply with study requirements Exclusion Criteria: * Current use or use within 365 days from Day 1 of any hepatocyte targeted siRNA or antisense oligonucleotide molecule * Active pancreatitis within 12 weeks prior to Day 1 * 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 Day 1 * Major surgery within 12 weeks of Day 1 or planned surgery during the study * Planned coronary intervention (e.g., stent placement or heart bypass) during 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 Day 1 * History of bleeding diathesis or coagulopathy * Current diagnosis of nephrotic syndrome * Systemic use of corticosteroids or anabolic steroids within 4 weeks prior to Day 1 or planned use during the study * 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 (24)

Research Site 5

Huntington Park, California, United States

Outcomes

Primary Outcomes

Percent Change From Baseline in Fasting TG at Week 24

Time frame: Baseline, Week 24

Secondary Outcomes

Percent Change From Baseline in Fasting TG Over Time

Time frame: Baseline, up to Week 36 (double-blind treatment period)

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

Time frame: Baseline, Week 24

Percent Change From Baseline in Fasting Non-HDL-C Over Time

Time frame: Baseline, up to Week 36 (double-blind treatment period)

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

Time frame: Baseline, Week 24

Percent Change From Baseline in Fasting Total ApoB Over Time

Time frame: Baseline, up to Week 36 (double-blind treatment period)

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

Time frame: Baseline, Week 24

Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time

Time frame: Baseline, up to Week 36 (double-blind treatment period)

Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24

Time frame: Baseline, Week 24

Percent Change From Baseline in ANGPTL3 Over Time

Data from ClinicalTrials.gov

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Hialeah, Florida, United States

Research Site 17

Miami, Florida, United States

Research Site 8

Port Orange, Florida, United States

Research Site 24

Minneapolis, Minnesota, United States

Research Site 10

Omaha, Nebraska, United States

Research Site 23

Las Vegas, Nevada, United States

Research Site 22

New York, New York, United States

Research Site 15

Greensboro, North Carolina, United States

Research Site 2

Morehead City, North Carolina, United States

...and 14 more locations

Time frame: Baseline, up to Week 36 (double-blind treatment period)

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

Time frame: Baseline, Week 24

Percent Change From Baseline in Fasting HDL-C Over Time

Time frame: Baseline, up to Week 36 (double-blind treatment period)

Plasma Pharmacokinetic (PK) Concentration for ARO-ANG3 Over Time in the Double-Blind Treatment Period

Time frame: Baseline, Day 1: pre-dose, 15 minutes, 1, 3, 6 hours post-dose; Day 2: 24 hours post-dose; Week 12: pre-dose, 15 minutes, 1, 3, 6, 24 hours post-dose (double-blind treatment period)

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24

TEAEs are adverse events (AEs) that occur following IP administration or a pre-existing condition exacerbated following IP administration. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious adverse event (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.

Time frame: From first dose of IP up to Week 24

Number of Participants With TEAEs and/or SAEs Over Time in the Double-Blind Treatment Period

Adverse event (AE)=any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. TEAEs=AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. Serious adverse event (SAE)= 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; is a medically important event or reaction.

Time frame: up to Week 36 (double-blind treatment period)

Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension (OLE) Period

Time frame: From first dose of study drug in the OLE up to Month 24 (open-label extension)

Percent Change From Baseline in Fasting TG Over Time in the Open Label Extension (OLE) Period

Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

Percent Change From Baseline in Fasting Non-HDL-C Over Time in the Open Label Extension (OLE) Period

Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

Percent Change From Baseline in Fasting Total ApoB Over Time in the Open Label Extension (OLE) Period

Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time in the Open Label Extension (OLE) Period

Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

Percent Change From Baseline in ANGPTL3 Over Time in the Open Label Extension (OLE) Period

Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)

Percent Change From Baseline in Fasting HDL-C Over Time in the Open Label Extension (OLE) Period

Time frame: Baseline, OLE Baseline, Months 1-24 (open-label extension)