Clinical trial NCT03362242: Study of ARO-AAT in Normal Adult Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alpha 1-Antitrypsin Deficiency
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-12-05
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment
timeFrame: 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:
measure: Pharmacokinetics (PK) of ARO-AAT: Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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
measure: PK of ARO-AAT: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
measure: PK of ARO-AAT: Terminal Elimination Half-Life (t½)
timeFrame: Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
measure: PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24)
timeFrame: Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
measure: PK of ARO-AAT: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf)
timeFrame: Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose
measure: Percent Change in Serum Alpha-1 Antitrypsin (AAT) Levels From Day 1 Pre-Dose Baseline to Nadir
timeFrame: Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days
measure: Duration of Response of Serum AAT levels From Nadir Back to Above 20% of Baseline or Above 90 mg/dL
timeFrame: Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days
Other outcomes:
Locations:
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies Limited
state: Auckland
Study officials:
References: