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Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH) (Gateway)

Primary Purpose

Homozygous Familial Hypercholesterolemia

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARO-ANG 3 Injection
Sponsored by
Arrowhead Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Homozygous Familial Hypercholesterolemia

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Fasting LDL-C >100 mg/dL at Screening
  • Weight of ≥ 40 kg and body mass index ≥ 18.5 and ≤ 40 kg/m2
  • Diagnosis of HoFH based on a supportive genetic test or clinical diagnosis
  • On stable maximally tolerated lipid lowering therapy
  • Willing to abide by stable low-fat, low-cholesterol, heart-healthy diet for at least 4 weeks prior to Day 1
  • Participants of childbearing potential (males & females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the 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 medications 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 small interfering RNA oligonucleotides (siRNA) or antisense oligonucleoside molecule
  • Use of evinacumab (some exceptions apply)
  • Fasting TG > 300 mg/dL at Screening
  • Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins
  • Newly diagnosed (within 3 months prior to informed consent) or poorly controlled diabetes (Hemoglobin A1c > 9%)
  • Use of systemic corticosteroids (some exceptions apply)
  • Symptoms of myocardial ischemia or severe left ventricular dysfunction
  • History of malignancy within 3 years of Day 1 (some exceptions apply)
  • Planned cardiac procedure/surgery such as coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI), carotid surgery or stenting, or carotid revascularization

Note: additional inclusion/exclusion criteria may apply per protocol

Sites / Locations

  • Icahn School of Medicine at Mt. Sinai
  • Metabolic and Atherosclerosis Research Center
  • Royal Prince Alfred Hospital
  • Linear Clinical Research
  • Ecogene-21
  • Clinique des Maladies Lipidiques de Quebec Inc
  • WCR-Lipids, Carbohydrate Metabolism Unit Area 551, Department of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ARO-ANG3 Dose 1

ARO-ANG3 Dose 2

Arm Description

ARO-ANG3 Dose Level 1 subcutaneous (SC)

ARO-ANG3 Dose Level 2 SC

Outcomes

Primary Outcome Measures

Percent Change from Baseline in Fasting Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) and LDL-C by Preparative Ultracentrifugation (LDL-C [PUC]) up to Week 24

Secondary Outcome Measures

Percent Change from Baseline in Fasting LDL-C (PUC) Over Time
Absolute Change from Baseline in Fasting LDL-C (PUC) Over Time
Percent Change from Baseline in Fasting Calculated LDL-C Over Time
Absolute Change from Baseline in Fasting Calculated LDL-C Over Time
Percent Change from Baseline in Fasting Angiopoietin-like 3 (ANGPTL3) Over Time
Absolute Change from Baseline in Fasting ANGPTL3 Over Time
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) Over Time
Absolute Change from Baseline in Fasting Total ApoB Over Time
Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) Over Time
Absolute Change from Baseline in Fasting HDL-C Over Time
Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Over Time
Absolute Change from Baseline in Fasting Non-HDL-C Over Time
Percent Change from Baseline in Fasting Very-Low-Density Lipoprotein-Cholesterol (VLDL-C) Over Time
Absolute Change from Baseline in VLDL-C Over Time
Percent Change from Baseline in Fasting Total Cholesterol (TC) Over Time
Absolute Change from Baseline in Fasting TC Over Time
Percent Change from Baseline in Fasting Triglycerides (TG) Over Time
Absolute Change from Baseline in Fasting TG Over Time
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Number of Participants with Anti-Drug Antibodies (ADAs) to ARO-ANG3 Over Time
Proportion of Participants meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C ≥ 300 mg/dL at Week 24
Proportion of Participants Meeting European Union (EU) Apheresis Eligibility Criteria per German Apheresis Working Group at Week 24

Full Information

First Posted
January 20, 2022
Last Updated
August 21, 2023
Sponsor
Arrowhead Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05217667
Brief Title
Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)
Acronym
Gateway
Official Title
Phase 2 Study to Evaluate the Safety and Efficacy of ARO-ANG3 in Subjects With Homozygous Familial Hypercholesterolemia (HOFH)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 22, 2022 (Actual)
Primary Completion Date
May 2, 2023 (Actual)
Study Completion Date
May 2025 (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
No

5. Study Description

Brief Summary
Participants with documented homozygous familial hypercholesterolemia (HoFH) who have provided informed consent will receive 2 open-label doses of ARO-ANG3 and be evaluated for safety and efficacy parameters through 36 weeks. Participants who complete the first 36 week treatment period may opt to continue in an additional 24-month extension period during which they will receive up to 8 doses open-label doses of ARO-ANG3.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Homozygous Familial Hypercholesterolemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ARO-ANG3 Dose 1
Arm Type
Experimental
Arm Description
ARO-ANG3 Dose Level 1 subcutaneous (SC)
Arm Title
ARO-ANG3 Dose 2
Arm Type
Experimental
Arm Description
ARO-ANG3 Dose Level 2 SC
Intervention Type
Drug
Intervention Name(s)
ARO-ANG 3 Injection
Intervention Description
Participants will be randomized to receive ARO-ANG3 SC on Day 1 and Day 84 during the initial 36 Weeks of the study and on Day1 and Months 3, 6, 9, 12, 15, 18, and 21 of the extension period
Primary Outcome Measure Information:
Title
Percent Change from Baseline in Fasting Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) and LDL-C by Preparative Ultracentrifugation (LDL-C [PUC]) up to Week 24
Time Frame
Baseline, up to Week 24
Secondary Outcome Measure Information:
Title
Percent Change from Baseline in Fasting LDL-C (PUC) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in Fasting LDL-C (PUC) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting Calculated LDL-C Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in Fasting Calculated LDL-C Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting Angiopoietin-like 3 (ANGPTL3) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in Fasting ANGPTL3 Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting Total Apolipoprotein B (ApoB) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in Fasting Total ApoB Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting High-Density Lipoprotein-Cholesterol (HDL-C) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period) 36
Title
Absolute Change from Baseline in Fasting HDL-C Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in Fasting Non-HDL-C Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting Very-Low-Density Lipoprotein-Cholesterol (VLDL-C) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in VLDL-C Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting Total Cholesterol (TC) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in Fasting TC Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Percent Change from Baseline in Fasting Triglycerides (TG) Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Absolute Change from Baseline in Fasting TG Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Number of Participants with Anti-Drug Antibodies (ADAs) to ARO-ANG3 Over Time
Time Frame
Baseline, up to Week 36 (initial treatment period), up to Month 24 (extension period)
Title
Proportion of Participants meeting United States National Lipid Association Apheresis Eligibility Criteria of LDL-C ≥ 300 mg/dL at Week 24
Time Frame
Week 24
Title
Proportion of Participants Meeting European Union (EU) Apheresis Eligibility Criteria per German Apheresis Working Group at Week 24
Time Frame
Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Fasting LDL-C >100 mg/dL at Screening Weight of ≥ 40 kg and body mass index ≥ 18.5 and ≤ 40 kg/m2 Diagnosis of HoFH based on a supportive genetic test or clinical diagnosis On stable maximally tolerated lipid lowering therapy Willing to abide by stable low-fat, low-cholesterol, heart-healthy diet for at least 4 weeks prior to Day 1 Participants of childbearing potential (males & females) must agree to use highly-effective contraception during the study and for at least 24 weeks from the 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 medications 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 small interfering RNA oligonucleotides (siRNA) or antisense oligonucleoside molecule Use of evinacumab (some exceptions apply) Fasting TG > 300 mg/dL at Screening Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins Newly diagnosed (within 3 months prior to informed consent) or poorly controlled diabetes (Hemoglobin A1c > 9%) Use of systemic corticosteroids (some exceptions apply) Symptoms of myocardial ischemia or severe left ventricular dysfunction History of metastatic malignancy within 3 years of Day 1 (some exceptions apply) Planned cardiac procedure/surgery such as coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI), carotid surgery or stenting, or carotid revascularization Note: additional inclusion/exclusion criteria may apply per protocol
Facility Information:
Facility Name
Icahn School of Medicine at Mt. Sinai
City
Mount Sinai
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Metabolic and Atherosclerosis Research Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45227
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Linear Clinical Research
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Ecogene-21
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Clinique des Maladies Lipidiques de Quebec Inc
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1V 4W2
Country
Canada
Facility Name
WCR-Lipids, Carbohydrate Metabolism Unit Area 551, Department of Medicine
City
Johannesburg
ZIP/Postal Code
2193
Country
South Africa

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)

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