Study of ARO-AAT in Normal Adult Volunteers

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03362242
• Date of registration: 30/11/2017
• Prospective Registration: Yes
• Primary sponsor: Arrowhead Pharmaceuticals
• Public title: Study of ARO-AAT in Normal Adult Volunteers
• Scientific 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
• Date of first enrolment: March 12, 2018
• Target sample size: 45
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03362242
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

New Zealand

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alpha 1-Antitrypsin Deficiency

Intervention(s)

Other: Sterile Normal Saline (0.9% NaCl)

Drug: ARO-AAT Injection

Primary Outcome(s)

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 Outcome(s)

Pharmacokinetics (PK) of ARO-AAT: Maximum Observed Plasma Concentration (Cmax) [Time Frame: 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 [Time Frame: 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 24 Hours (AUC0-24) [Time Frame: 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) [Time Frame: Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose]

PK of ARO-AAT: Time to Maximum Plasma Concentration (Tmax) [Time Frame: Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose]

Duration of Response of Serum AAT levels From Nadir Back to Above 20% of Baseline or Above 90 mg/dL [Time Frame: Part A (SAD phase): up to 29 (+/- 2) days; Part B (MAD phase): up to 113 (+/- 2) days]

PK of ARO-AAT: Terminal Elimination Half-Life (t½) [Time Frame: Part A (SAD phase): up to 48 hours post-dose; Part B (MAD phase): up to 48 hours post-dose]

Secondary ID(s)

AROAAT1001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors