Alpha 1-Antitrypsin Deficiency
Conditions
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.
Interventions
DRUGARO-AAT Injection
Single or multiple doses of ARO-AAT by subcutaneous (sc) injections
OTHERSterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
New Zealand
Outcome results
None listed