Study of Fazirsiran (TAK-999, ARO-AAT) in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)

Arrowhead Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Alpha 1-Antitrypsin Deficiency

Treatments: Drug: ARO-AAT

Study type: Interventional

Funder types: Industry

Identifiers

NCT03946449

2019-000068-86 (EudraCT Number)

AROAAT2002

Details and patient eligibility

About

The purpose of this study is to evaluate the the safety and efficacy of the investigational product, fazirsiran (TAK-999, ARO-AAT), administered subcutaneously to patients with alpha-1 antitrypsin deficiency associated liver disease (AATD).

Full description

Participants will be enrolled to receive multiple subcutaneous injections of fazirsiran (TAK-999, ARO-AAT). All eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. All participants will undergo an end of study (EOS) biopsy. Treated participants will be offered the opportunity to continue treatment in an open label extension during which they will undergo a final biopsy.

Enrollment: 16 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of AATD
• Liver biopsy indicating Metavir F1-F3 liver fibrosis based on local pathology read.
• Women of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use contraception
• Willing to provide written informed consent and to comply with study requirements
• Non-smoker for at least 1 year
• No abnormal finding of clinical relevance at screening

Exclusion criteria

• Clinically significant health concerns other than AATD
• Previous diagnosis or diagnosis at Screening of definitive liver cirrhosis
• 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 involving therapeutic intervention
• Use of illicit drugs within 1 year prior to Screening

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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16 participants in 3 patient groups

ARO-AAT 100 mg Cohort 1b

Experimental group

Description:

Primary Study Period (6-12 months): 100 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 100 mg dose of subcutaneous AROAAT every 12 weeks (Q12W). Treatment Extension II (up to 24 Months): 100 mg dose of subcutaneous ARO-AAT Q12W.

Treatment:

Drug: ARO-AAT

ARO-AAT 200 mg Cohort 1

Experimental group

Description:

Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 3 doses, with 2 optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous AROAAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.

Treatment:

Drug: ARO-AAT

ARO-AAT 200 mg Cohort 2

Experimental group

Description:

Primary Study Period (6-12 months): 200 mg dose of subcutaneous ARO-AAT for a minimum of 5 doses, with optional treatment extension periods. Treatment Extension I (12 months): 200 mg dose of subcutaneous AROAAT Q12W. Treatment Extension II (up to 24 Months): 200 mg dose of subcutaneous ARO-AAT Q12W.

Treatment:

Drug: ARO-AAT