Study of ARO-APOC3 in Adults With Mixed Dyslipidemia

Mixed Dyslipidemia Clinical Trial

— MUIR  

Official title:

A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Mixed Dyslipidemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04998201
• Other study ID #: AROAPOC3-2002
• Secondary ID: 2021-000688-57
• Status: Completed
• Phase: Phase 2
• Start date: September 28, 2021
• Est. completion date: August 14, 2023

Study information

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

Clinical Trial Summary

Participants who have met all protocol eligibility criteria will be randomly assigned to treatment (ARO-APOC3 or placebo) in a double-blind fashion and will be evaluted for safety and efficacy over 48 weeks. Participants will be counseled to remain on a specified diet throughout the study, as recommended by the Investigator in accordance with local standard of care. After week 48, participants will be eligible and invited to consent and continue in an open-label extension study. All placebo participants who opt to continue will switch to active drug (ARO-APOC3) during the extension study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: August 14, 2023
• Est. primary completion date: February 10, 2023
• 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 on more than one occasion

• Fasting levels at Screening of non-HDL-C = 100 mg/dL OR LDL-C = 70 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 14 days apart
• Willing to follow diet counseling as per Investigator judgment based on local standard of care
• Participants of childbearing potential (males & females) must use highly-effective contraception during the study and for at least 24 weeks following the last dose of study medication. Males must not donate sperm and females must ot donate eggs during the study and for at least 24 weeks following the last dose of study medication.
• Women of childbearing potential must have a negative pregnancy test at Screening 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
• 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 through end of study
• Acute coronary syndrome event within 24 weeks of Day 1
• Major surgery within 12 weeks of Day 1
• Planned coronary intervention (e.g., stent placement or heart bypass) during the study
• New York Heart Association Class II, III or IV heart failure or last known ejection fraction of <30%
• Uncontrolled hypertension
• Known history of 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-APOC3
ARO-APOC3 Injection
• Placebo
Sterile Normal Saline (0.9% NaCl)

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Health	Clayton	Victoria
Australia	Genesis Care Joondalup	Joondalup	Western Australia
Australia	University of Sunshine Coast Morayfield	Morayfield	Queensland
Canada	LMC Diabetes & Endocrinology	Concord	Ontario
Canada	Institut de Recherches Cliniques de Montreal	Montréal	Quebec
Hungary	DRC Gyogyszervizsgalo	Balatonfüred
Hungary	University of Debrecen-Clinical Center	Debrecen
Hungary	Borbanya Praxis Kft.	Nyiregyhaza
New Zealand	Middlemore Hospital	Auckland
New Zealand	Southern Clinical Trials Christchurch	Christchurch
Poland	All-MED Centrum Medyczne	Lódz
Poland	Instytut Centrum Zdrowia Matki Polki	Lódz
Poland	Praktyka Lekarska Ewa Krzyzagorska	Poznan
Poland	Centrum Medyczne Medyk	Rzeszów
United States	Westside Medical Associates of Los Angeles	Beverly Hills	California
United States	Preventive Cardiology Inc.	Boca Raton	Florida
United States	Primed Clinical Research	Dayton	Ohio
United States	Alta Pharmaceutical Research Center	Dunwoody	Georgia
United States	Invesclinic U.S.; LLC	Fort Lauderdale	Florida
United States	Prestige Clinical Research	Franklin	Ohio
United States	Tribe Clinical Research	Greenville	South Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	East Texas Cardiology PA	Houston	Texas
United States	Clinical Research of South Nevada	Las Vegas	Nevada
United States	Ocean Blue Medical Research Center, Inc.	Miami Springs	Florida
United States	Mid Hudson Medical Research, PLLC	New Windsor	New York
United States	Valley Clinical Trials, Inc	Northridge	California
United States	A & R Research Group	Pembroke Pines	Florida
United States	BFHC Research	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Arrowhead Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hungary,  New Zealand,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24		Baseline, Week 24
Secondary	Percent Change from Baseline in Fasting TG		Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 36, Week 48
Secondary	Percent Change from Baseline in Apolipoprotein (APO) C-III at Week 24		Baseline, Week 24
Secondary	Percent Change from Baseline in APOC-III Over Time		Baseline, up to Week 48
Secondary	Percent Change from Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24		Baseline, Week 24
Secondary	Percent Change form Baseline in Non-HDL-C Over Time		Baseline, up to Week 48
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 HDL-C Over Time		Baseline, up to Week 48
Secondary	Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24		Baseline, Week 24
Secondary	Percent Change from Baseline in ApoB Over Time		Baseline, up to Week 48
Secondary	Percent Change from Baseline in Fasting Total Low Density Lipoprotein Cholesterol (LDL-C) Using Ultracentrifugation at Week 24		Baseline, Week 24
Secondary	Percent Change from Baseline in Fasting Total LDL-C Using Ultracentrifugation Over Time		Baseline, up to Week 48
Secondary	Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Week 24		Week 24
Secondary	Number of Participants with Treatment- Emergent AEs and/or SAEs Through Week 48		up to Week 48
Secondary	Change from Baseline in Plasma Concentrations of ARO-APOC3 Over Time		up to Week 24
Secondary	Pharmacokinetics (PK) of ARO-APOC3: Maximum Observed Plasma Concentration (Cmax)		up to Week 24
Secondary	PK of ARO-APOC3: Time to Maximum Plasma Concentration (Tmax)		up to Week 24
Secondary	PK of ARO-APOC3: Area Under the Plasma Concentration Versus Time Curve From Zero to Time of Last Measurable Concentration (AUClast)		up to Week 24