Study of ARO-ANG3 in Adults With Mixed Dyslipidemia

Mixed Dyslipidemia Clinical Trial

— ARCHES-2  

Official title:

A Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-ANG3 in Adults With Mixed Dyslipidemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04832971
• Other study ID #: AROANG3-2001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 28, 2021
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Arrowhead Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 204
• Est. completion date: December 2024
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dyslipidemias
• Mixed Dyslipidemia

Intervention

Drug:
• ARO-ANG3
ARO-ANG3 Injection
• Placebo
Sterile Normal Saline (0.9% NaCl)

Locations

Country	Name	City	State
Australia	Paratus Clinical Research	Blacktown	New South Wales
Australia	Linear Clinical Research	Nedlands
Australia	University of the Sunshine Coast Clinical Trials Centre	Sippy Downs	Queensland
Canada	Centre d'Etudes Cliniques	Chicoutimi	Quebec
Canada	Lawson Health Research Institute	London	Ontario
Canada	Ctr de Recherche Clin de Laval	Québec
Canada	Recherche Clinique Sigma Inc	Québec
New Zealand	Lakeland Clinical Trials - Waitemata	Birkenhead
New Zealand	NZCR OpCo Ltd.	Christchurch
New Zealand	Lakeland Clinical Trials - Waikato	Hamilton
New Zealand	Lakeland Clinical Trials - Rotorua	Rotorua
United States	Capital Area Research, LLC	Camp Hill	Pennsylvania
United States	Medication Management LLC	Greensboro	North Carolina
United States	AGA Clinical Trials	Hialeah	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Velocity Clinical Research	Huntington Park	California
United States	Clinical Research of South Nevada	Las Vegas	Nevada
United States	Marion Area Health Center	Marion	Ohio
United States	Global Research Solutions	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Lucas Research, Inc.	Morehead City	North Carolina
United States	Icahn School of Medicine at Mount Sinai (ISMMS)	New York	New York
United States	Methodist Physicians Clinic Heart Consultants	Omaha	Nebraska
United States	Progressive Medical Research	Port Orange	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Fasting TG at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in Fasting TG Over Time		Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Secondary	Percent Change From Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in Fasting Non-HDL-C Over Time		Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Secondary	Percent Change From Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in Fasting Total ApoB Over Time		Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Secondary	Percent Change From Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in Fasting LDL-C Using Ultracentrifugation Over Time		Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Secondary	Percent Change From Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in ANGPTL3 Over Time		Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Secondary	Percent Change From Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24		Baseline, Week 24
Secondary	Percent Change From Baseline in Fasting HDL-C Over Time		Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Secondary	Plasma Concentrations of ARO-ANG3 Over Time		Baseline, up to Week 12 (double-blind treatment period), up to Month 24 (open-label extension)
Secondary	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.	From first dose of IP up to Week 24
Secondary	Number of Participants With AEs and/or SAEs Over Time in the Double-Blind Treatment Period		up to Week 36 (double-blind treatment period)
Secondary	Number of Participants With AEs and/or SAEs Over Time in the Open-Label Extension		up to Month 24 (open-label extension)