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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: Belcesiran

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Must be 18 to 75 years of age inclusive, at the time of signing the Informed Consent Form (ICF).
2. Documented diagnosis of PiZZ-type Alpha-1 Antitrypsin deficiency (AATD), confirmed by genotyping.
3. Lung, renal and liver function within acceptable limits.
4. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

1. 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
2. Routine use of acetaminophen/paracetamol
3. Use of systemically acting steroids in the month prior to Screening and throughout the study period.
4. Positive SARS-CoV-2 virus test at Screening
5. Any other safety laboratory test result considered clinically significant and unacceptable by the Investigator
6. Inability or unwillingness to comply with the specified study procedures, including lifestyle considerations

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: belcesiran; Participants who completed the DCR-A1AT-201 treatment period will receive open-label belcesiran administered subcutaneously	Drug: Belcesiran; Belcesiran will be administered subcutaneously (SC) in the treatment arm.
No Intervention: Observational; 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?

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	Time Frame
Changes in serum AAT protein concentrations over time	up to 152 weeks

Collaborators and Investigators

• Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Investigators: Study Director: Anne-Sophie Sejling, MD, Dicerna Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2021
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): May 23, 2022

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 23, 2021
• First Posted (Actual): December 7, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 10, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Liver Diseases; Alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: DCR-A1AT-202; STARLIGHT (Other Identifier: Dicerna Pharmaceuticals)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No