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

Alpha 1-Antitrypsin Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05146882
• Other study ID #: DCR-A1AT-202
• Secondary ID: STARLIGHT
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2021
• Est. completion date: May 23, 2022

Study information

• Verified date: June 2022
• Source: Dicerna Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: May 23, 2022
• Est. primary completion date: May 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Liver Diseases

Intervention

Drug:
• Belcesiran
Belcesiran will be administered subcutaneously (SC) in the treatment arm.

Locations

Country	Name	City	State
New Zealand	Auckland Clinical Studies	Grafton	Auckland

Sponsors (1)

Lead Sponsor	Collaborator
Dicerna Pharmaceuticals, Inc.

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of treatment-emergent adverse events		up to 152 weeks
Primary	The change from baseline in pulmonary function tests (PFTs)	Forced expiratory volume in 1 second (FEV1)	up to 152 weeks
Primary	The change from baseline in PFTs	Forced vital capacity (FVC)	up to 152 weeks
Primary	The change from baseline in PFTs	FEV1/FVC	up to 152 weeks
Primary	The change from baseline in PFTs	diffusing capacity for carbon monoxide (DLCO)	up to 152 weeks
Primary	The change from baseline in 12-lead electrocardiogram (ECG)	heart rate	up to 56 weeks
Primary	The change from baseline in ECG	ventricular rate	up to 56 weeks
Primary	The change from baseline in 12-lead ECG	RR interval	up to 56 weeks
Primary	The change from baseline in 12-lead ECG	PR interval	up to 56 weeks
Primary	The change from baseline in 12-lead ECG	QRS duration	up to 56 weeks
Primary	The change from baseline in 12-lead ECG	QT interval	up to 56 weeks
Primary	The change from baseline in 12-lead ECG	corrected QT interval (QTcF, Fridericia correction)	up to 56 weeks
Primary	The change from baseline in physical examination (PE) findings	body weight	up to 56 weeks
Primary	The change from baseline in PE findings	body-mass index (BMI) (using height from DCR-A1AT-201 study)	up to 56 weeks
Primary	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
Primary	The change from baseline in vital sign measurements	blood pressure	up to 56 weeks
Primary	The change from baseline in vital sign measurements	pulse rate	up to 56 weeks
Primary	The change from baseline in vital sign measurements	respiratory rate	up to 56 weeks
Primary	The change from baseline in vital sign measurements	oral temperature	up to 56 weeks
Primary	The change from baseline in clinical laboratory tests: Hematology	Hematology is collected to evaluate the long-term safety of belcesiran	up to 152 weeks
Primary	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
Primary	The change from baseline in clinical laboratory tests: Coagulation	Coagulation is collected to evaluate the long-term safety of belcesiran	up to 152 weeks
Primary	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	Changes in serum AAT protein concentrations over time		up to 152 weeks