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

Arrowhead Pharmaceuticals1 site in 1 country45 target enrollmentMarch 12, 2018

ConditionsAlpha 1-Antitrypsin Deficiency

InterventionsARO-AAT Injection Sterile Normal Saline (0.9% NaCl)

DrugsARO-AAT Injection

Overview

Phase: Phase 1
Intervention: ARO-AAT Injection
Conditions: Alpha 1-Antitrypsin Deficiency
Sponsor: Arrowhead Pharmaceuticals
Enrollment: 45
Locations: 1
Primary Endpoint: Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment
Status: Completed
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

March 12, 2018

End Date

March 21, 2020

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Arrowhead Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

ARO-AAT

Intervention: ARO-AAT Injection

Placebo

Intervention: Sterile Normal Saline (0.9% NaCl)

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment

Time Frame: 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 Outcomes

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)