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

• ClinicalTrials.gov Identifier: NCT05146882
• Recruitment Status: Withdrawn
• First Posted: December 7, 2021
• Last Update Posted: June 27, 2022
• Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Information provided by (Responsible Party): Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Tracking Information

• First Submitted Date: November 9, 2021
• First Posted Date: December 7, 2021
• Last Update Posted Date: June 27, 2022
• Estimated Study Start Date: December 2021
• Actual Primary Completion Date: May 23, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 23, 2021)

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

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 23, 2021): Changes in serum AAT protein concentrations over time [ Time Frame: up to 152 weeks ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Extension Study of Belcesiran in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATLD)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Alpha 1-Antitrypsin Deficiency

Intervention

Drug: Belcesiran

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

Study Arms

• Experimental: belcesiran
  Participants who completed the DCR-A1AT-201 treatment period will receive open-label belcesiran administered subcutaneously
  Intervention: Drug: Belcesiran
• 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)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: June 22, 2022): 0
• Original Estimated Enrollment (submitted: November 23, 2021): 54
• Actual Study Completion Date: May 23, 2022
• Actual Primary Completion Date: May 23, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: New Zealand

Administrative Information

• NCT Number: NCT05146882
• Other Study ID Numbers: DCR-A1AT-202; STARLIGHT ( Other Identifier: Dicerna Pharmaceuticals )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Original Responsible Party: Same as current
• Current Study Sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Anne-Sophie Sejling, MD; Dicerna Pharmaceuticals

• PRS Account: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Verification Date: June 2022