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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04998201




Registration number
NCT04998201
Ethics application status
Date submitted
3/08/2021
Date registered
10/08/2021
Date last updated
18/04/2024

Titles & IDs
Public title
Study of ARO-APOC3 in Adults With Mixed Dyslipidemia
Scientific title
A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Mixed Dyslipidemia
Secondary ID [1] 0 0
2021-000688-57
Secondary ID [2] 0 0
AROAPOC3-2002
Universal Trial Number (UTN)
Trial acronym
MUIR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mixed Dyslipidemia 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARO-APOC3
Treatment: Drugs - Placebo

Experimental: ARO-APOC3 10 mg, Day 1 and Week 12 - 2 doses of ARO-APOC3 by subcutaneous (sc) injection

Experimental: ARO-APOC3 25 mg, Day 1 and Week 12 - 2 doses of ARO-APOC3 by subcutaneous (sc) injection

Experimental: ARO-APOC3 50 mg, Day 1 and Week 12 - 2 doses of ARO-APOC3 by subcutaneous (sc) injection

Experimental: ARO-APOC3 50 mg, Day 1 and Week 24 - 2 doses of ARO-APOC3 by subcutaneous (sc) injection

Placebo comparator: Placebo, Day 1 and Week 12 or Week 24 - calculated volume to match active treatment by sc injection


Treatment: Drugs: ARO-APOC3
ARO-APOC3 Injection

Treatment: Drugs: Placebo
Sterile Normal Saline (0.9% NaCl)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Percent Change from Baseline in Fasting TG
Timepoint [1] 0 0
Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 36, Week 48
Secondary outcome [2] 0 0
Percent Change from Baseline in Apolipoprotein (APO) C-III at Week 24
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Percent Change from Baseline in APOC-III Over Time
Timepoint [3] 0 0
Baseline, up to Week 48
Secondary outcome [4] 0 0
Percent Change from Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Percent Change form Baseline in Non-HDL-C Over Time
Timepoint [5] 0 0
Baseline, up to Week 48
Secondary outcome [6] 0 0
Percent Change from Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 24
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Percent Change from Baseline in HDL-C Over Time
Timepoint [7] 0 0
Baseline, up to Week 48
Secondary outcome [8] 0 0
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Percent Change from Baseline in ApoB Over Time
Timepoint [9] 0 0
Baseline, up to Week 48
Secondary outcome [10] 0 0
Percent Change from Baseline in Fasting Total Low Density Lipoprotein Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Percent Change from Baseline in Fasting Total LDL-C Using Ultracentrifugation Over Time
Timepoint [11] 0 0
Baseline, up to Week 48
Secondary outcome [12] 0 0
Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Week 24
Timepoint [12] 0 0
Week 24
Secondary outcome [13] 0 0
Number of Participants with Treatment- Emergent AEs and/or SAEs Through Week 48
Timepoint [13] 0 0
up to Week 48
Secondary outcome [14] 0 0
Change from Baseline in Plasma Concentrations of ARO-APOC3 Over Time
Timepoint [14] 0 0
up to Week 24
Secondary outcome [15] 0 0
Pharmacokinetics (PK) of ARO-APOC3: Maximum Observed Plasma Concentration (Cmax)
Timepoint [15] 0 0
up to Week 24
Secondary outcome [16] 0 0
PK of ARO-APOC3: Time to Maximum Plasma Concentration (Tmax)
Timepoint [16] 0 0
up to Week 24
Secondary outcome [17] 0 0
PK of ARO-APOC3: Area Under the Plasma Concentration Versus Time Curve From Zero to Time of Last Measurable Concentration (AUClast)
Timepoint [17] 0 0
up to Week 24

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/08/2023
Sample size
Target
Accrual to date
Final
353
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
University of Sunshine Coast Morayfield - Morayfield
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Genesis Care Joondalup - Joondalup
Recruitment postcode(s) [1] 0 0
4506 - Morayfield
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
6027 - Joondalup
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Nevada
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Hungary
State/province [11] 0 0
Balatonfüred
Country [12] 0 0
Hungary
State/province [12] 0 0
Debrecen
Country [13] 0 0
Hungary
State/province [13] 0 0
Nyiregyhaza
Country [14] 0 0
New Zealand
State/province [14] 0 0
Auckland
Country [15] 0 0
New Zealand
State/province [15] 0 0
Christchurch
Country [16] 0 0
Poland
State/province [16] 0 0
Poznan
Country [17] 0 0
Poland
State/province [17] 0 0
Rzeszów
Country [18] 0 0
Poland
State/province [18] 0 0
Lódz

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04998201
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04998201