Study of ARO-APOC3 in Healthy Volunteers, Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome (FCS)

• ClinicalTrials.gov Identifier: NCT03783377
• Recruitment Status: Completed
• First Posted: December 21, 2018
• Last Update Posted: March 3, 2021
• Sponsor: Arrowhead Pharmaceuticals
• Information provided by (Responsible Party): Arrowhead Pharmaceuticals

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple doses of ARO-APOC3 in healthy adult volunteers and in patients with severe hypertriglyceridemia and familial chylomicronemia syndrome (FCS).

Condition or disease	Intervention/treatment	Phase
Hypertriglyceridemia; Familial Chylomicronemia	Drug: ARO-APOC3; Drug: sterile normal saline (0.9% NaCl)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of ARO-APOC3 in Adult Healthy Volunteers as Well as in Severely Hypertriglyceridemic Patients and Patients With Familial Chylomicronemia Syndrome
• Actual Study Start Date: March 8, 2019
• Actual Primary Completion Date: February 11, 2021
• Actual Study Completion Date: February 11, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: ARO-APOC3	Drug: ARO-APOC3; single or multiple doses of ARO-APOC3 by subcutaneous (sc) injections
Placebo Comparator: Placebo	Drug: sterile normal saline (0.9% NaCl); calculated volume to match active treatment

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment [ Time Frame: Up to Day 113 (+/- 3 days) ]

Secondary Outcome Measures :

1. Pharmacokinetics (PK) of ARO-APOC3 in Normal Healthy Volunteers (NHVs): Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Single dose phase: Up to 48 hours post-dose ]
2. PK of ARO-APOC3 in NHVs: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Single dose phase: Up to 48 hours post-dose ]
3. PK of ARO-APOC3 in NHVs: Terminal Elimination Half-Life (t1/2) [ Time Frame: Single dose phase: Up to 48 hours post-dose ]
4. PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) [ Time Frame: Single dose phase: Up to 48 hours post-dose ]
5. PK of ARO-APOC3 in NHVs: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) [ Time Frame: Single dose phase: Up to 48 hours post-dose ]
6. Reduction in Fasting Serum APOC3 from Pre-Dose Baseline [ Time Frame: Up to Day 113 (+/- 3 days) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• Normal electrocardiogram (ECG) at screening
• Hypertriglyceridemic patients must have a history of fasting serum triglycerides of at least 300 mg/dL (3.38 mmol/L) at screening or verifiable diagnosis of FCS

Exclusion Criteria:

• Clinically significant health concerns
• Regular use of alcohol within one month prior to Screening
• Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
• Recent use of illicit drugs
• Use of more than two tobacco/nicotine containing or cannabis products per month within 6 months prior to drug administration (applicable only to Normal Healthy Volunteers)

Note: additional inclusion/exclusion criteria may apply, per protocol

Contacts and Locations

Locations

Australia, New South Wales

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia, 2050

Australia, Queensland

University of the Sunshine Coast Clinical Trial Centre

Sippy Downs, Queensland, Australia

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Australia, Western Australia

Linear Clinical Research

Perth, Western Australia, Australia, 6009

Canada, Ontario

Robarts Research Institute

London, Ontario, Canada, N6A 5B7

Canada, Quebec

Ecogene-21

Chicoutimi, Quebec, Canada, G7H 7K9

Institute de Recherches Cliniques de Montreal

Montreal, Quebec, Canada, H2W 1R7

New Zealand

Auckland Clinical Studies Limited

Grafton, Auckland, New Zealand, 1010

Middlemore Hospital

Papatoetoe, Auckland, New Zealand, 2025

Lipid & Diabetes Research Group

Christchurch, New Zealand, 8011

Sponsors and Collaborators

Arrowhead Pharmaceuticals

More Information

• Responsible Party: Arrowhead Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03783377
• Other Study ID Numbers: AROAPOC31001
• First Posted: December 21, 2018
• Last Update Posted: March 3, 2021
• Last Verified: March 2021

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
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Hyperlipoproteinemia Type I; Hypertriglyceridemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hyperlipoproteinemias