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

Primary Purpose

Alpha 1-Antitrypsin Deficiency

Status
Withdrawn
Phase
Phase 2
Locations
New Zealand
Study Type
Interventional
Intervention
Belcesiran
Sponsored by
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Alpha 1-Antitrypsin Deficiency

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Auckland Clinical Studies

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

belcesiran

Observational

Arm Description

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

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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Changes in serum AAT protein concentrations over time

Full Information

First Posted
November 9, 2021
Last Updated
June 22, 2022
Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
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1. Study Identification

Unique Protocol Identification Number
NCT05146882
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Update to Program Design - No Participants Enrolled
Study Start Date
December 2021 (Anticipated)
Primary Completion Date
May 23, 2022 (Actual)
Study Completion Date
May 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha 1-Antitrypsin Deficiency

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
belcesiran
Arm Type
Experimental
Arm Description
Participants who completed the DCR-A1AT-201 treatment period will receive open-label belcesiran administered subcutaneously
Arm Title
Observational
Arm Type
No Intervention
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Belcesiran
Intervention Description
Belcesiran will be administered subcutaneously (SC) in the treatment arm.
Primary Outcome Measure Information:
Title
The incidence of treatment-emergent adverse events
Time Frame
up to 152 weeks
Title
The change from baseline in pulmonary function tests (PFTs)
Description
Forced expiratory volume in 1 second (FEV1)
Time Frame
up to 152 weeks
Title
The change from baseline in PFTs
Description
Forced vital capacity (FVC)
Time Frame
up to 152 weeks
Title
The change from baseline in PFTs
Description
FEV1/FVC
Time Frame
up to 152 weeks
Title
The change from baseline in PFTs
Description
diffusing capacity for carbon monoxide (DLCO)
Time Frame
up to 152 weeks
Title
The change from baseline in 12-lead electrocardiogram (ECG)
Description
heart rate
Time Frame
up to 56 weeks
Title
The change from baseline in ECG
Description
ventricular rate
Time Frame
up to 56 weeks
Title
The change from baseline in 12-lead ECG
Description
RR interval
Time Frame
up to 56 weeks
Title
The change from baseline in 12-lead ECG
Description
PR interval
Time Frame
up to 56 weeks
Title
The change from baseline in 12-lead ECG
Description
QRS duration
Time Frame
up to 56 weeks
Title
The change from baseline in 12-lead ECG
Description
QT interval
Time Frame
up to 56 weeks
Title
The change from baseline in 12-lead ECG
Description
corrected QT interval (QTcF, Fridericia correction)
Time Frame
up to 56 weeks
Title
The change from baseline in physical examination (PE) findings
Description
body weight
Time Frame
up to 56 weeks
Title
The change from baseline in PE findings
Description
body-mass index (BMI) (using height from DCR-A1AT-201 study)
Time Frame
up to 56 weeks
Title
The change from baseline in PE findings
Description
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
Time Frame
up to 56 weeks
Title
The change from baseline in vital sign measurements
Description
blood pressure
Time Frame
up to 56 weeks
Title
The change from baseline in vital sign measurements
Description
pulse rate
Time Frame
up to 56 weeks
Title
The change from baseline in vital sign measurements
Description
respiratory rate
Time Frame
up to 56 weeks
Title
The change from baseline in vital sign measurements
Description
oral temperature
Time Frame
up to 56 weeks
Title
The change from baseline in clinical laboratory tests: Hematology
Description
Hematology is collected to evaluate the long-term safety of belcesiran
Time Frame
up to 152 weeks
Title
The change from baseline in clinical laboratory tests: Clinical Chemistry
Description
Clinical Chemistry is collected to evaluate the long-term safety of belcesiran
Time Frame
up to 152 weeks
Title
The change from baseline in clinical laboratory tests: Coagulation
Description
Coagulation is collected to evaluate the long-term safety of belcesiran
Time Frame
up to 152 weeks
Title
The change from baseline in clinical laboratory tests: Urinalysis
Description
Urinalysis is collected to evaluate the long-term safety of belcesiran
Time Frame
up to 152 weeks
Secondary Outcome Measure Information:
Title
Changes in serum AAT protein concentrations over time
Time Frame
up to 152 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne-Sophie Sejling, MD
Organizational Affiliation
Dicerna Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Auckland Clinical Studies
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1010
Country
New Zealand

12. IPD Sharing Statement

Learn more about this trial

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

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