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

NCT05146882 | Withdrawn Phase 2 DMC

• 2 other identifiers: DCR-A1AT-202STARLIGHT
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alpha 1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (23)

• 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 Outcomes (1)

• Changes in serum AAT protein concentrations over time

  up to 152 weeks

Study Arms (2)

belcesiran

EXPERIMENTAL

Participants who completed the DCR-A1AT-201 treatment period will receive open-label belcesiran administered subcutaneously

Drug: Belcesiran

Observational

NO INTERVENTION

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)

Interventions

Belcesiran DRUG

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

belcesiran

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dicerna Pharmaceuticals, Inc., a Novo Nordisk company: lead

Study Sites (1)

Auckland Clinical Studies

Grafton, Auckland, 1010, New Zealand

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Anne-Sophie Sejling, MD

  Dicerna Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2021
• First Posted: December 7, 2021
• Study Start: December 1, 2021
• Primary Completion: May 23, 2022
• Study Completion: May 23, 2022
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

NZ (1)