ARCHES-2: Study of ARO-ANG3 in Adults With Mixed Dyslipidemia
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ARO-ANG3 Two doses of ARO-ANG3 by subcutaneous (sc) injection during double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period. |
Drug: ARO-ANG3
ARO-ANG3 Injection
|
| Placebo Comparator: Placebo Calculated volume to match active treatment by sc injection during the double-blind treatment period. Up to 8 doses of ARO-ANG3 by sc injection during the open-label extension period. |
Drug: ARO-ANG3
ARO-ANG3 Injection
Drug: Placebo
Sterile Normal Saline (0.9% NaCl)
|
Outcome Measures
Primary Outcome Measures
- Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24 [Baseline, Week 24]
Secondary Outcome Measures
- 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)]
- Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24 [Baseline, Week 24]
- 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)]
- Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24 [Baseline, Week 24]
- 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)]
- Percent Change from Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24 [Baseline, Week 24]
- 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)]
- Percent Change from Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24 [Baseline, Week 24]
- Percent Change from Baseline in ANGPTL3 Over Time [Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)]
- Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24 [Baseline, Week 24]
- 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)]
- Plasma Concentrations of ARO-ANG3 Over Time [Baseline, up to Week 12 (double-blind treatment period), up to Month 24 (open-label extension)]
- Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Week 24 [Week 24]
- Number of Participants with AEs and/or SAEs Over Time in the Double-Blind Treatment Period [up to Week 36 (double-blind treatment period)]
- Number of Participants with AEs and/or SAEs Over Time in the Open-Label Extension [up to Month 24 (open-label extension)]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Velocity Clinical Research | Huntington Park | California | United States | 90255 |
| 2 | AGA Clinical Trials | Hialeah | Florida | United States | 33012 |
| 3 | Global Research Solutions | Miami | Florida | United States | 33144 |
| 4 | Progressive Medical Research | Port Orange | Florida | United States | 32127 |
| 5 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 6 | Methodist Physicians Clinic Heart Consultants | Omaha | Nebraska | United States | 68114 |
| 7 | Clinical Research of South Nevada | Las Vegas | Nevada | United States | 89121 |
| 8 | Icahn School of Medicine at Mount Sinai (ISMMS) | New York | New York | United States | 10029 |
| 9 | Medication Management LLC | Greensboro | North Carolina | United States | 27408 |
| 10 | Lucas Research, Inc. | Morehead City | North Carolina | United States | 28557 |
| 11 | Marion Area Health Center | Marion | Ohio | United States | 43302 |
| 12 | Capital Area Research, LLC | Camp Hill | Pennsylvania | United States | 17011 |
| 13 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 14 | Paratus Clinical Research | Blacktown | New South Wales | Australia | 2148 |
| 15 | University of the Sunshine Coast Clinical Trials Centre | Sippy Downs | Queensland | Australia | 4556 |
| 16 | Linear Clinical Research | Nedlands | Australia | 6009 | |
| 17 | Lawson Health Research Institute | London | Ontario | Canada | N6A 5A5 |
| 18 | Centre d'Etudes Cliniques | Chicoutimi | Quebec | Canada | G7H 7K9 |
| 19 | Recherche Clinique Sigma Inc | Québec | Canada | G1G 3Z4 | |
| 20 | Ctr de Recherche Clin de Laval | Québec | Canada | H7T2P5 | |
| 21 | Lakeland Clinical Trials - Waitemata | Birkenhead | New Zealand | 0626 | |
| 22 | NZCR OpCo Ltd. | Christchurch | New Zealand | 8011 | |
| 23 | Lakeland Clinical Trials - Waikato | Hamilton | New Zealand | 3200 | |
| 24 | Lakeland Clinical Trials - Rotorua | Rotorua | New Zealand | 3010 |
Sponsors and Collaborators
- Arrowhead Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AROANG3-2001