Study of ARO-ANG3 in Adults With Mixed Dyslipidemia (ARCHES-2)
Primary Purpose
Mixed Dyslipidemia
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARO-ANG3
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Mixed Dyslipidemia
Eligibility 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
Sites / Locations
- Velocity Clinical Research
- AGA Clinical Trials
- Global Research Solutions
- Progressive Medical Research
- University of Minnesota
- Methodist Physicians Clinic Heart Consultants
- Clinical Research of South Nevada
- Icahn School of Medicine at Mount Sinai (ISMMS)
- Medication Management LLC
- Lucas Research, Inc.
- Marion Area Health Center
- Capital Area Research, LLC
- Baylor College of Medicine
- Paratus Clinical Research
- University of the Sunshine Coast Clinical Trials Centre
- Linear Clinical Research
- Lawson Health Research Institute
- Centre d'Etudes Cliniques
- Recherche Clinique Sigma Inc
- Ctr de Recherche Clin de Laval
- Lakeland Clinical Trials - Waitemata
- NZCR OpCo Ltd.
- Lakeland Clinical Trials - Waikato
- Lakeland Clinical Trials - Rotorua
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ARO-ANG3
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24
Secondary Outcome Measures
Percent Change from Baseline in Fasting TG Over Time
Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
Percent Change from Baseline in Fasting Non-HDL-C Over Time
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
Percent Change from Baseline in Fasting Total ApoB Over Time
Percent Change from Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
Percent Change from Baseline in Fasting LDL-C Using Ultracentrifugation Over Time
Percent Change from Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24
Percent Change from Baseline in ANGPTL3 Over Time
Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24
Percent Change from Baseline in Fasting HDL-C Over Time
Plasma Concentrations of ARO-ANG3 Over Time
Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Week 24
Number of Participants with AEs and/or SAEs Over Time in the Double-Blind Treatment Period
Number of Participants with AEs and/or SAEs Over Time in the Open-Label Extension
Full Information
NCT ID
NCT04832971
First Posted
April 2, 2021
Last Updated
October 21, 2022
Sponsor
Arrowhead Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04832971
Brief Title
Study of ARO-ANG3 in Adults With Mixed Dyslipidemia
Acronym
ARCHES-2
Official Title
A Double-blind, Placebo-controlled Phase 2b Study to Evaluate the Efficacy and Safety of ARO-ANG3 in Adults With Mixed Dyslipidemia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 28, 2021 (Actual)
Primary Completion Date
August 30, 2022 (Actual)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mixed Dyslipidemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
204 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARO-ANG3
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ARO-ANG3
Intervention Description
ARO-ANG3 Injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sterile Normal Saline (0.9% NaCl)
Primary Outcome Measure Information:
Title
Percent Change from Baseline in Fasting Triglycerides (TG) at Week 24
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
Percent Change from Baseline in Fasting TG Over Time
Time Frame
Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Title
Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) at Week 24
Time Frame
Baseline, Week 24
Title
Percent Change from Baseline in Fasting Non-HDL-C Over Time
Time Frame
Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Title
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) at Week 24
Time Frame
Baseline, Week 24
Title
Percent Change from Baseline in Fasting Total ApoB Over Time
Time Frame
Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Title
Percent Change from Baseline in Fasting Low-density Lipoprotein-Cholesterol (LDL-C) Using Ultracentrifugation at Week 24
Time Frame
Baseline, Week 24
Title
Percent Change from Baseline in Fasting LDL-C Using Ultracentrifugation Over Time
Time Frame
Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Title
Percent Change from Baseline in Angiopoietin-like Protein 3 (ANGPTL3) at Week 24
Time Frame
Baseline, Week 24
Title
Percent Change from Baseline in ANGPTL3 Over Time
Time Frame
Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Title
Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) at Week 24
Time Frame
Baseline, Week 24
Title
Percent Change from Baseline in Fasting HDL-C Over Time
Time Frame
Baseline, up to Week 36 (double-blind treatment period), up to Month 24 (open-label extension)
Title
Plasma Concentrations of ARO-ANG3 Over Time
Time Frame
Baseline, up to Week 12 (double-blind treatment period), up to Month 24 (open-label extension)
Title
Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) at Week 24
Time Frame
Week 24
Title
Number of Participants with AEs and/or SAEs Over Time in the Double-Blind Treatment Period
Time Frame
up to Week 36 (double-blind treatment period)
Title
Number of Participants with AEs and/or SAEs Over Time in the Open-Label Extension
Time Frame
up to Month 24 (open-label extension)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Velocity Clinical Research
City
Huntington Park
State/Province
California
ZIP/Postal Code
90255
Country
United States
Facility Name
AGA Clinical Trials
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
Global Research Solutions
City
Miami
State/Province
Florida
ZIP/Postal Code
33144
Country
United States
Facility Name
Progressive Medical Research
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Methodist Physicians Clinic Heart Consultants
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Clinical Research of South Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89121
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai (ISMMS)
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Medication Management LLC
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27408
Country
United States
Facility Name
Lucas Research, Inc.
City
Morehead City
State/Province
North Carolina
ZIP/Postal Code
28557
Country
United States
Facility Name
Marion Area Health Center
City
Marion
State/Province
Ohio
ZIP/Postal Code
43302
Country
United States
Facility Name
Capital Area Research, LLC
City
Camp Hill
State/Province
Pennsylvania
ZIP/Postal Code
17011
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Paratus Clinical Research
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Facility Name
University of the Sunshine Coast Clinical Trials Centre
City
Sippy Downs
State/Province
Queensland
ZIP/Postal Code
4556
Country
Australia
Facility Name
Linear Clinical Research
City
Nedlands
ZIP/Postal Code
6009
Country
Australia
Facility Name
Lawson Health Research Institute
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
Centre d'Etudes Cliniques
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Recherche Clinique Sigma Inc
City
Québec
ZIP/Postal Code
G1G 3Z4
Country
Canada
Facility Name
Ctr de Recherche Clin de Laval
City
Québec
ZIP/Postal Code
H7T2P5
Country
Canada
Facility Name
Lakeland Clinical Trials - Waitemata
City
Birkenhead
ZIP/Postal Code
0626
Country
New Zealand
Facility Name
NZCR OpCo Ltd.
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Facility Name
Lakeland Clinical Trials - Waikato
City
Hamilton
ZIP/Postal Code
3200
Country
New Zealand
Facility Name
Lakeland Clinical Trials - Rotorua
City
Rotorua
ZIP/Postal Code
3010
Country
New Zealand
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of ARO-ANG3 in Adults With Mixed Dyslipidemia
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