MedPath

Study of ARO-ANG3 in Adults With Mixed Dyslipidemia

Phase 2
Completed
Conditions
Mixed Dyslipidemia
Interventions
Drug: Placebo
Registration Number
NCT04832971
Lead Sponsor
Arrowhead Pharmaceuticals
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
204
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ARO-ANG3 100 mgARO-ANG3Two doses of ARO-ANG3 bysc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.
ARO-ANG3 200 mgARO-ANG3Two doses of ARO-ANG3 by sc injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.
PlaceboARO-ANG3Calculated volume to match active treatment by sc injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.
PlaceboPlaceboCalculated volume to match active treatment by sc injection at Day 1 and Week 12 during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.
ARO-ANG3 50 mgARO-ANG3Two doses of ARO-ANG3 by subcutaneous (sc) injection at Day 1 and Week 12 during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period.
Primary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Fasting TG at Week 24Baseline, Week 24
Secondary Outcome Measures
NameTimeMethod
Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over TimeBaseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24Baseline, Week 24
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and/or Serious TEAEs up to Week 24From first dose of IP 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.

Number of Participants With AEs and/or SAEs Over Time in the Double-Blind Treatment Periodup to Week 36 (double-blind treatment period)
Percent Change From Baseline in Fasting TG Over TimeBaseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Percent Change From Baseline in ANGPTL3 Over TimeBaseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24Baseline, Week 24
Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24Baseline, Week 24
Plasma Concentrations of ARO-ANG3 Over TimeBaseline, up to Week 12 (double-blind treatment period), up to Month 24 (open-label extension)
Percent Change From Baseline in Fasting Non-HDL-C Over TimeBaseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24Baseline, Week 24
Percent Change From Baseline in Fasting Total ApoB Over TimeBaseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24Baseline, Week 24
Percent Change From Baseline in Fasting HDL-C Over TimeBaseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extensionup to Month 24 (open-label extension)

Trial Locations

Locations (24)

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

AGA Clinical Trials

🇺🇸

Hialeah, Florida, United States

Medication Management LLC

🇺🇸

Greensboro, North Carolina, United States

Marion Area Health Center

🇺🇸

Marion, Ohio, United States

Paratus Clinical Research

🇦🇺

Blacktown, New South Wales, Australia

NZCR OpCo Ltd.

🇳🇿

Christchurch, New Zealand

University of the Sunshine Coast Clinical Trials Centre

🇦🇺

Sippy Downs, Queensland, Australia

Linear Clinical Research

🇦🇺

Nedlands, Australia

Recherche Clinique Sigma Inc

🇨🇦

Québec, Canada

Ctr de Recherche Clin de Laval

🇨🇦

Québec, Canada

Lakeland Clinical Trials - Rotorua

🇳🇿

Rotorua, New Zealand

Clinical Research of South Nevada

🇺🇸

Las Vegas, Nevada, United States

Methodist Physicians Clinic Heart Consultants

🇺🇸

Omaha, Nebraska, United States

Velocity Clinical Research

🇺🇸

Huntington Park, California, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Global Research Solutions

🇺🇸

Miami, Florida, United States

Icahn School of Medicine at Mount Sinai (ISMMS)

🇺🇸

New York, New York, United States

Lucas Research, Inc.

🇺🇸

Morehead City, North Carolina, United States

Capital Area Research, LLC

🇺🇸

Camp Hill, Pennsylvania, United States

Centre d'Etudes Cliniques

🇨🇦

Chicoutimi, Quebec, Canada

Lawson Health Research Institute

🇨🇦

London, Ontario, Canada

Lakeland Clinical Trials - Waitemata

🇳🇿

Birkenhead, New Zealand

Lakeland Clinical Trials - Waikato

🇳🇿

Hamilton, New Zealand

Progressive Medical Research

🇺🇸

Port Orange, Florida, United States

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