An Extension Study of Belcesiran in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATLD)

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, open-label extension of Study DCR-A1AT-201, designed to evaluate the long-term safety and further characterize the pharmacodynamics (PD) of belcesiran in adult patients with PiZZ AATLD.

Official Title
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A Phase 2 Open-Label Extension Study to Evaluate the Safety and Pharmacodynamics of Belcesiran in Patients With PiZZ Alpha-1 Antitrypsin Deficiency Associated Liver Disease

Conditions
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Alpha 1-Antitrypsin Deficiency

Intervention / Treatment
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* Drug: Belcesiran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be 18 to 75 years of age inclusive, at the time of signing the Informed Consent Form (ICF). Documented diagnosis of PiZZ-type Alpha-1 Antitrypsin deficiency (AATD), confirmed by genotyping. Lung, renal and liver function within acceptable limits. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Exclusion Criteria: Any condition that, in the opinion of the Investigator, would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study Routine use of acetaminophen/paracetamol Use of systemically acting steroids in the month prior to Screening and throughout the study period. Positive SARS-CoV-2 virus test at Screening Any other safety laboratory test result considered clinically significant and unacceptable by the Investigator Inability or unwillingness to comply with the specified study procedures, including lifestyle considerations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: belcesiran<br>Participants who completed the DCR-A1AT-201 treatment period will receive open-label belcesiran administered subcutaneously | Drug: Belcesiran<br>* Belcesiran will be administered subcutaneously (SC) in the treatment arm.<br>|
| No Intervention: Observational<br>Participants who completed the DCR-A1AT-201 Conditional Follow-up period will enter DCR-A1AT-202 for continued follow-up (will not receive open-label belcesiran) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of treatment-emergent adverse events |  | up to 152 weeks | 
| The change from baseline in pulmonary function tests (PFTs) | Forced expiratory volume in 1 second (FEV1) | up to 152 weeks | 
| The change from baseline in PFTs | Forced vital capacity (FVC) | up to 152 weeks | 
| The change from baseline in PFTs | FEV1/FVC | up to 152 weeks | 
| The change from baseline in PFTs | diffusing capacity for carbon monoxide (DLCO) | up to 152 weeks | 
| The change from baseline in 12-lead electrocardiogram (ECG) | heart rate | up to 56 weeks | 
| The change from baseline in ECG | ventricular rate | up to 56 weeks | 
| The change from baseline in 12-lead ECG | RR interval | up to 56 weeks | 
| The change from baseline in 12-lead ECG | PR interval | up to 56 weeks | 
| The change from baseline in 12-lead ECG | QRS duration | up to 56 weeks | 
| The change from baseline in 12-lead ECG | QT interval | up to 56 weeks | 
| The change from baseline in 12-lead ECG | corrected QT interval (QTcF, Fridericia correction) | up to 56 weeks | 
| The change from baseline in physical examination (PE) findings | body weight | up to 56 weeks | 
| The change from baseline in PE findings | body-mass index (BMI) (using height from DCR-A1AT-201 study) | up to 56 weeks | 
| The change from baseline in PE findings | physical examination to assess skin, lungs, cardiovascular system, and abdomen (liver and spleen) based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) grading scale | up to 56 weeks | 
| The change from baseline in vital sign measurements | blood pressure | up to 56 weeks | 
| The change from baseline in vital sign measurements | pulse rate | up to 56 weeks | 
| The change from baseline in vital sign measurements | respiratory rate | up to 56 weeks | 
| The change from baseline in vital sign measurements | oral temperature | up to 56 weeks | 
| The change from baseline in clinical laboratory tests: Hematology | Hematology is collected to evaluate the long-term safety of belcesiran | up to 152 weeks | 
| The change from baseline in clinical laboratory tests: Clinical Chemistry | Clinical Chemistry is collected to evaluate the long-term safety of belcesiran | up to 152 weeks | 
| The change from baseline in clinical laboratory tests: Coagulation | Coagulation is collected to evaluate the long-term safety of belcesiran | up to 152 weeks | 
| The change from baseline in clinical laboratory tests: Urinalysis | Urinalysis is collected to evaluate the long-term safety of belcesiran | up to 152 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum AAT protein concentrations over time |  | up to 152 weeks |