Study of ARO-AAT in Normal Adult Volunteers

A Phase 1 Single and Multiple Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Effect of ARO-AAT on Serum Alpha-1 Antitrypsin Levels in Normal Adult Volunteers

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-AAT in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: ARO-AAT Injection; Other: Sterile Normal Saline (0.9% NaCl)

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Women of child bearing 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
• Non-smoker for at least one year
• Normal lung function
• No abnormal finding of clinical relevance at Screening
• Normal AAT level at Screening visit

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 any drugs or dietary/herbal supplements know to interfere with liver metabolism

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Sterile Normal Saline (0.9% NaCl); Calculated volume to match active comparator
Active Comparator: ARO-AAT	Drug: ARO-AAT Injection; Single or multiple doses of ARO-AAT by subcutaneous (sc) injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment	Part A (single-ascending dose [SAD] phase): up to 29 (+/- 2) days post-dose; Part B (multiple-ascending dose [MAD] phase): up to 113 (+/- 2) days post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK) of ARO-AAT: Maximum Observed Plasma Concentration (Cmax)	Part A (single-ascending dose [SAD] phase): up to 48 hours post-dose; Part B (multiple-ascending dose [MAD] phase): up to 48 hours post-dose
PK of ARO-AAT: Time to Maximum Plasma Concentration (Tmax)	Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
PK of ARO-AAT: Terminal Elimination Half-Life (t½)	Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)	Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)	Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
Percent Change in Serum Alpha-1 Antitrypsin (AAT) Levels From Day 1 Pre-Dose Baseline to Nadir	Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days
Duration of Response of Serum AAT levels From Nadir Back to Above 20% of Baseline or Above 90 mg/dL	Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2018
• Primary Completion (Actual): October 23, 2018
• Study Completion (Actual): March 21, 2020

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 5, 2017

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 17, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: AROAAT1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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