Clinical trial NCT04998201: Study of ARO-APOC3 in Adults With Mixed Dyslipidemia
Official title: A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 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: 2021-08-10
Enrollment: 353
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: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percent Change from Baseline in Fasting TG
timeFrame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 36, Week 48
measure: Percent Change from Baseline in Apolipoprotein (APO) C-III at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change from Baseline in APOC-III Over Time
timeFrame: Baseline, up to Week 48
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 form Baseline in Non-HDL-C Over Time
timeFrame: Baseline, up to Week 48
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 HDL-C Over Time
timeFrame: Baseline, up to Week 48
measure: Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change from Baseline in ApoB Over Time
timeFrame: Baseline, up to Week 48
measure: Percent Change from Baseline in Fasting Total Low Density Lipoprotein Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
timeFrame: Baseline, Week 24
measure: Percent Change from Baseline in Fasting Total LDL-C Using Ultracentrifugation Over Time
timeFrame: Baseline, up to Week 48
measure: Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Week 24
timeFrame: Week 24
measure: Number of Participants with Treatment- Emergent AEs and/or SAEs Through Week 48
timeFrame: up to Week 48
measure: Change from Baseline in Plasma Concentrations of ARO-APOC3 Over Time
timeFrame: up to Week 24
measure: Pharmacokinetics (PK) of ARO-APOC3: Maximum Observed Plasma Concentration (Cmax)
timeFrame: up to Week 24
measure: PK of ARO-APOC3: Time to Maximum Plasma Concentration (Tmax)
timeFrame: up to Week 24
measure: PK of ARO-APOC3: Area Under the Plasma Concentration Versus Time Curve From Zero to Time of Last Measurable Concentration (AUClast)
timeFrame: up to Week 24
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc
state: California
city: Boca Raton
country: United States
facility: Preventive Cardiology Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: Invesclinic U.S.; LLC
state: Florida
city: Miami Springs
country: United States
facility: Ocean Blue Medical Research Center, Inc.
state: Florida
city: Pembroke Pines
country: United States
facility: A & R Research Group
state: Florida
city: Dunwoody
country: United States
facility: Alta Pharmaceutical Research Center
state: Georgia
city: Las Vegas
country: United States
facility: Clinical Research of South Nevada
state: Nevada
city: New Windsor
country: United States
facility: Mid Hudson Medical Research, PLLC
state: New York
city: Dayton
country: United States
facility: Primed Clinical Research
state: Ohio
city: Franklin
country: United States
facility: Prestige Clinical Research
state: Ohio
city: Greenville
country: United States
facility: Tribe Clinical Research
state: South Carolina
city: Houston
country: United States
facility: East Texas Cardiology PA
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: BFHC Research
state: Texas
city: Morayfield
country: Australia
facility: University of Sunshine Coast Morayfield
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Joondalup
country: Australia
facility: Genesis Care Joondalup
state: Western Australia
city: Concord
country: Canada
facility: LMC Diabetes & Endocrinology
state: Ontario
city: Montréal
country: Canada
facility: Institut de Recherches Cliniques de Montreal
state: Quebec
city: Balatonfüred
country: Hungary
facility: DRC Gyogyszervizsgalo
city: Debrecen
country: Hungary
facility: University of Debrecen-Clinical Center
city: Nyiregyhaza
country: Hungary
facility: Borbanya Praxis Kft.
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Christchurch
country: New Zealand
facility: Southern Clinical Trials Christchurch
city: Poznań
country: Poland
facility: Praktyka Lekarska Ewa Krzyzagorska
city: Rzeszów
country: Poland
facility: Centrum Medyczne Medyk
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Łódź
country: Poland
facility: All-MED Centrum Medyczne
Study officials:
References: