Study of ARO-APOC3 in Adults With Mixed Dyslipidemia (MUIR)
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| ClinicalTrials.gov Identifier: NCT04998201 |
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Recruitment Status :
Completed
First Posted : August 10, 2021
Last Update Posted : April 18, 2024
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Sponsor:
Arrowhead Pharmaceuticals
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Mixed Dyslipidemia | Drug: ARO-APOC3 Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 353 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-APOC3 in Adults With Mixed Dyslipidemia |
| Actual Study Start Date : | September 28, 2021 |
| Actual Primary Completion Date : | February 10, 2023 |
| Actual Study Completion Date : | August 14, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: ARO-APOC3 10 mg, Day 1 and Week 12
2 doses of ARO-APOC3 by subcutaneous (sc) injection
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Drug: ARO-APOC3
ARO-APOC3 Injection |
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Experimental: ARO-APOC3 25 mg, Day 1 and Week 12
2 doses of ARO-APOC3 by subcutaneous (sc) injection
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Drug: ARO-APOC3
ARO-APOC3 Injection |
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Experimental: ARO-APOC3 50 mg, Day 1 and Week 12
2 doses of ARO-APOC3 by subcutaneous (sc) injection
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Drug: ARO-APOC3
ARO-APOC3 Injection |
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Experimental: ARO-APOC3 50 mg, Day 1 and Week 24
2 doses of ARO-APOC3 by subcutaneous (sc) injection
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Drug: ARO-APOC3
ARO-APOC3 Injection |
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Placebo Comparator: Placebo, Day 1 and Week 12 or Week 24
calculated volume to match active treatment by sc injection
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Drug: Placebo
Sterile Normal Saline (0.9% NaCl) |
Primary Outcome Measures :
- Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24 [ Time Frame: Baseline, Week 24 ]
Secondary Outcome Measures :
- Percent Change from Baseline in Fasting TG [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 36, Week 48 ]
- Percent Change from Baseline in Apolipoprotein (APO) C-III at Week 24 [ Time Frame: Baseline, Week 24 ]
- Percent Change from Baseline in APOC-III Over Time [ Time Frame: Baseline, up to Week 48 ]
- Percent Change from Baseline in Fasting Non High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 [ Time Frame: Baseline, Week 24 ]
- Percent Change form Baseline in Non-HDL-C Over Time [ Time Frame: Baseline, up to Week 48 ]
- Percent Change from Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 24 [ Time Frame: Baseline, Week 24 ]
- Percent Change from Baseline in HDL-C Over Time [ Time Frame: Baseline, up to Week 48 ]
- Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 [ Time Frame: Baseline, Week 24 ]
- Percent Change from Baseline in ApoB Over Time [ Time Frame: Baseline, up to Week 48 ]
- Percent Change from Baseline in Fasting Total Low Density Lipoprotein Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 [ Time Frame: Baseline, Week 24 ]
- Percent Change from Baseline in Fasting Total LDL-C Using Ultracentrifugation Over Time [ Time Frame: Baseline, up to Week 48 ]
- Number of Participants with Treatment-Emergent Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Week 24 [ Time Frame: Week 24 ]
- Number of Participants with Treatment- Emergent AEs and/or SAEs Through Week 48 [ Time Frame: up to Week 48 ]
- Change from Baseline in Plasma Concentrations of ARO-APOC3 Over Time [ Time Frame: up to Week 24 ]
- Pharmacokinetics (PK) of ARO-APOC3: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: up to Week 24 ]
- PK of ARO-APOC3: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: up to Week 24 ]
- PK of ARO-APOC3: Area Under the Plasma Concentration Versus Time Curve From Zero to Time of Last Measurable Concentration (AUClast) [ Time Frame: up to Week 24 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04998201
Locations
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Sponsors and Collaborators
Arrowhead Pharmaceuticals
| Responsible Party: | Arrowhead Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04998201 |
| Other Study ID Numbers: |
AROAPOC3-2002 2021-000688-57 ( EudraCT Number ) |
| First Posted: | August 10, 2021 Key Record Dates |
| Last Update Posted: | April 18, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases |