Clinical trial NCT04832971: Study of ARO-ANG3 in Adults With Mixed Dyslipidemia
Official title: A Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-ANG3 in Adults With Mixed Dyslipidemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mixed Dyslipidemia
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-04-06
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Based on medical history, evidence of 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

Primary outcomes:
measure: Percent Change From Baseline in Fasting TG at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percent Change From Baseline in Fasting TG Over Time
timeFrame: Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
measure: Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Fasting Non-HDL-C Over Time
timeFrame: Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
measure: Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Fasting Total ApoB Over Time
timeFrame: Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
measure: Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time
timeFrame: Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
measure: Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in ANGPTL3 Over Time
timeFrame: Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
measure: Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change From Baseline in Fasting HDL-C Over Time
timeFrame: Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
measure: Plasma Concentrations of ARO-ANG3 Over Time
timeFrame: Baseline, up to Week 12 (double-blind treatment period), up to Month 24 (open-label extension)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24
timeFrame: From first dose of IP up to Week 24
measure: Number of Participants With AEs and/or SAEs Over Time in the Double-Blind Treatment Period
timeFrame: up to Week 36 (double-blind treatment period)
measure: Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension
timeFrame: up to Month 24 (open-label extension)
Other outcomes:
Locations:
city: Huntington Park
country: United States
facility: Velocity Clinical Research
state: California
city: Hialeah
country: United States
facility: AGA Clinical Trials
state: Florida
city: Miami
country: United States
facility: Global Research Solutions
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Omaha
country: United States
facility: Methodist Physicians Clinic Heart Consultants
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research of South Nevada
state: Nevada
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai (ISMMS)
state: New York
city: Greensboro
country: United States
facility: Medication Management LLC
state: North Carolina
city: Morehead City
country: United States
facility: Lucas Research, Inc.
state: North Carolina
city: Marion
country: United States
facility: Marion Area Health Center
state: Ohio
city: Camp Hill
country: United States
facility: Capital Area Research, LLC
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Blacktown
country: Australia
facility: Paratus Clinical Research
state: New South Wales
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast Clinical Trials Centre
state: Queensland
city: Nedlands
country: Australia
facility: Linear Clinical Research
city: London
country: Canada
facility: Lawson Health Research Institute
state: Ontario
city: Chicoutimi
country: Canada
facility: Centre d'Etudes Cliniques
state: Quebec
city: Québec
country: Canada
facility: Recherche Clinique Sigma Inc
city: Québec
country: Canada
facility: Ctr de Recherche Clin de Laval
city: Birkenhead
country: New Zealand
facility: Lakeland Clinical Trials - Waitemata
city: Christchurch
country: New Zealand
facility: NZCR OpCo Ltd.
city: Hamilton
country: New Zealand
facility: Lakeland Clinical Trials - Waikato
city: Rotorua
country: New Zealand
facility: Lakeland Clinical Trials - Rotorua
Study officials:
References: