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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04764448




Registration number
NCT04764448
Ethics application status
Date submitted
27/01/2021
Date registered
21/02/2021
Date last updated
31/12/2024

Titles & IDs
Public title
A Study of Belcesiran in Patients With AATLD
Scientific title
A Phase 2, Randomized, Double-blind, Placebo-Controlled Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Two Dose Levels of Belcesiran in Patients With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease
Secondary ID [1] 0 0
DCR-A1AT-201
Universal Trial Number (UTN)
Trial acronym
ESTRELLA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alpha 1-Antitrypsin Deficiency 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Belcesiran
Other interventions - Placebo
Treatment: Drugs - Belcesiran
Other interventions - Placebo
Treatment: Drugs - Belcesiran
Other interventions - Placebo

Experimental: Belcesiran Cohort 1 -

Placebo comparator: Placebo Cohort 1 -

Experimental: Belcesiran Cohort 2 -

Placebo comparator: Placebo Cohort 2 -

Experimental: Belcesiran Cohort 3 -

Placebo comparator: Placebo Cohort 3 -


Treatment: Drugs: Belcesiran
Administered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 24 weeks. Extension offered to participants.

Other interventions: Placebo
Comparator: Placebo Cohort 1 Administered sterile normal saline (0.9% NaCl) matching volume of belcesiran by subcutaneous (sc) injection for 24 weeks. Extension offered to participants.

Treatment: Drugs: Belcesiran
Administered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 48 weeks. Extension offered to participants.

Other interventions: Placebo
Administered sterile normal saline (0.9% NaCl) matching volumes of belcesiran by subcutaneous (sc) injection for 48 weeks. Extension offered to participants.

Treatment: Drugs: Belcesiran
Administered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 96 weeks.

Other interventions: Placebo
Administered sterile normal saline (0.9% NaCl) matching volumes of belcesiran by subcutaneous (sc) injection for 96 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Up to 2.6 years
Primary outcome [2] 0 0
Number of Participants With TEAEs and SAEs
Timepoint [2] 0 0
Up to 2.6 years
Primary outcome [3] 0 0
Change From Baseline in Pulmonary Function Tests (PFTs): Forced Vital Capacity (FVC)
Timepoint [3] 0 0
Baseline (Day 1), week 96
Primary outcome [4] 0 0
Change From Baseline in PFT: Forced Expiratory Volume in One Second (FEV1)
Timepoint [4] 0 0
Baseline (Day 1), week 96
Primary outcome [5] 0 0
Change From Baseline in PFT: FEV1/FVC Ratio
Timepoint [5] 0 0
Baseline (Day 1), week 96
Primary outcome [6] 0 0
Change From Baseline in PFT: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Timepoint [6] 0 0
Baseline (Day 1), week 96
Primary outcome [7] 0 0
Change From Baseline in 12 -Lead Electrochardiograms (ECGs): Mean Heart Rate
Timepoint [7] 0 0
Baseline (Day 1), week 96
Primary outcome [8] 0 0
Change From Baseline in 12 -Lead ECGs: Mean Ventricular Rate
Timepoint [8] 0 0
Baseline (Day 1), week 96
Primary outcome [9] 0 0
Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval
Timepoint [9] 0 0
Baseline (Day 1), week 96
Primary outcome [10] 0 0
Number of Participants With Physical Examination Findings
Timepoint [10] 0 0
At week 96
Primary outcome [11] 0 0
Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure
Timepoint [11] 0 0
Baseline (Day 1), week 96
Primary outcome [12] 0 0
Change From Baseline in Vital Signs: Heart Rate
Timepoint [12] 0 0
Baseline (Day 1), week 96
Primary outcome [13] 0 0
Vital Signs: Height at Baseline
Timepoint [13] 0 0
Baseline (Day 1)
Primary outcome [14] 0 0
Change From Baseline in Vital Signs: Respiratory Rate
Timepoint [14] 0 0
Baseline (Day 1), week 96
Primary outcome [15] 0 0
Change From Baseline in Vital Signs: Temperature
Timepoint [15] 0 0
Baseline (Day 1), week 96
Primary outcome [16] 0 0
Change From Baseline in Vital Signs: Weight
Timepoint [16] 0 0
Baseline (Day 1), week 96
Primary outcome [17] 0 0
Change in Clinical Laboratory Tests: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Glutamate Dehydrogenase, Lactate Dehydrogenase, Biomarker Creatine Kinase (M30) and Biomarker Creatine Kinase (M65)
Timepoint [17] 0 0
Baseline (Day 1), week 96
Primary outcome [18] 0 0
Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin
Timepoint [18] 0 0
Baseline (Day 1), week 96
Primary outcome [19] 0 0
Change From Baseline in Clinical Laboratory Tests: Bilirubin, Creatinine and Direct Bilirubin
Timepoint [19] 0 0
Baseline (Day 1), week 96
Primary outcome [20] 0 0
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen
Timepoint [20] 0 0
Baseline (Day 1), week 96
Primary outcome [21] 0 0
Change From Baseline in Clinical Laboratory Tests: Gamma Glutamyl Transferase
Timepoint [21] 0 0
Baseline (Day 1), week 96
Primary outcome [22] 0 0
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Timepoint [22] 0 0
Baseline (Day 1), week 96
Primary outcome [23] 0 0
Change From Baseline in Clinical Laboratory Tests: Basophils/Leucocytes
Timepoint [23] 0 0
Baseline (Day 1), week 96
Primary outcome [24] 0 0
Change From Baseline in Clinical Laboratory Tests: Eosinophils/Leucocytes
Timepoint [24] 0 0
Baseline (Day 1), week 96
Primary outcome [25] 0 0
Change From Baseline in Clinical Laboratory Tests: Haematocrit
Timepoint [25] 0 0
Baseline (Day 1), week 96
Primary outcome [26] 0 0
Change From Baseline in Clinical Laboratory Tests: Lymphocytes/Leucocytes
Timepoint [26] 0 0
Baseline (Day 1), week 96
Primary outcome [27] 0 0
Change From Baseline in Clinical Laboratory Tests: Monocytes/Leucocytes
Timepoint [27] 0 0
Baseline (Day 1), week 96
Primary outcome [28] 0 0
Change From Baseline in Clinical Laboratory Tests: Neutrophils/Leucocytes
Timepoint [28] 0 0
Baseline (Day 1), week 96
Primary outcome [29] 0 0
Change From Baseline in Clinical Laboratory Tests: Reticulocytes/Erythrocytes
Timepoint [29] 0 0
Baseline (Day 1), week 96
Primary outcome [30] 0 0
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin Concentration and Haemoglobin
Timepoint [30] 0 0
Baseline (Day 1), week 96
Primary outcome [31] 0 0
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin
Timepoint [31] 0 0
Baseline (Day 1), week 96
Primary outcome [32] 0 0
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Volume
Timepoint [32] 0 0
Baseline (Day 1), week 96
Primary outcome [33] 0 0
Change From Baseline in Clinical Laboratory Tests: Erythrocytes
Timepoint [33] 0 0
Baseline (Day 1), week 96
Primary outcome [34] 0 0
Change From Baseline in Clinical Laboratory Tests: Specific Gravity
Timepoint [34] 0 0
Baseline (Day 1), week 96
Primary outcome [35] 0 0
Change From Baseline in Clinical Laboratory Tests: Urine Erythrocytes and Urine Leucocytes
Timepoint [35] 0 0
Baseline (Day 1), week 96
Primary outcome [36] 0 0
Change From Baseline in Clinical Laboratory Tests: Potential of Hydrogen (pH)
Timepoint [36] 0 0
Baseline (Day 1), week 96
Primary outcome [37] 0 0
Change From Baseline in Clinical Laboratory Tests: Activated Partial Thromboplastin Time and Prothrombin Time
Timepoint [37] 0 0
Baseline (Day 1), week 96
Primary outcome [38] 0 0
Change From Baseline in Clinical Laboratory Tests: Prothrombin International Normalized Ratio
Timepoint [38] 0 0
Baseline (Day 1), week 96
Primary outcome [39] 0 0
Change in Clinical Laboratory Tests: Alpha Fetoprotein, Biomarker Hyaluronic Acid, Biomarker Matrix Metalloproteinase 9, Biomarker Procollagen 3 N-Terminal Propeptide, Biomarker Tissue Inhibitor of Metalloproteinase 1, Complement C3a and Complement C5a
Timepoint [39] 0 0
Baseline (Day 1), week 96
Primary outcome [40] 0 0
Change From Baseline in Clinical Laboratory Tests: C-Reactive Protein
Timepoint [40] 0 0
Baseline (Day 1), week 96
Primary outcome [41] 0 0
Change From Baseline in Clinical Laboratory Tests: Complement Bb
Timepoint [41] 0 0
Baseline (Day 1), week 96
Primary outcome [42] 0 0
Change From Baseline in Clinical Laboratory Tests: Complement Total (CH50)
Timepoint [42] 0 0
Baseline (Day 1), week 96
Primary outcome [43] 0 0
Cohort 1: Change From Baseline in Serum Alpha-1 Antitrypsin (AAT) Protein Concentrations
Timepoint [43] 0 0
Baseline (Day 1), week 24
Primary outcome [44] 0 0
Cohort 2: Change From Baseline in Serum AAT Protein Concentrations
Timepoint [44] 0 0
Baseline (Day 1), week 48
Secondary outcome [1] 0 0
Change From Baseline in Liver Fibrosis Ishak Score
Timepoint [1] 0 0
Baseline (Day 1), week 48

Eligibility
Key inclusion criteria
* 18 to 75 years, inclusive, at the time of consent.
* Documented diagnosis of PiZZ-type alpha-1 antitrypsin deficiency, confirmed by genotyping. Historical genotyping data may be used, if available.
* AATD-associated liver disease documented by liver biopsy at Screening.
* Consent to undergo paired liver biopsies.
* 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of chronic liver disease other than non-alcoholic fatty liver disease from any cause other than PiZZ-type alpha-1 antitrypsin deficiency.
* Child-Pugh Score B or C.
* History of one single severe exacerbation of underlying lung disease in the year prior to randomization.
* History of clinically significant respiratory infections (including pneumonia and lower respiratory tract infections), as determined by the Investigator, in the 3 months prior to screening
* Use of an RNAi drug at any time.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/02/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/05/2024
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St Vincent's Hospital Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
South Carolina
Country [4] 0 0
Austria
State/province [4] 0 0
Innsbruck
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
France
State/province [7] 0 0
Pessac
Country [8] 0 0
Germany
State/province [8] 0 0
Aachen
Country [9] 0 0
Germany
State/province [9] 0 0
Kiel
Country [10] 0 0
Ireland
State/province [10] 0 0
Dublin
Country [11] 0 0
Netherlands
State/province [11] 0 0
Leiden
Country [12] 0 0
New Zealand
State/province [12] 0 0
Auckland
Country [13] 0 0
New Zealand
State/province [13] 0 0
Hamilton
Country [14] 0 0
Portugal
State/province [14] 0 0
Creixomil
Country [15] 0 0
Portugal
State/province [15] 0 0
Porto
Country [16] 0 0
Portugal
State/province [16] 0 0
Vila Real
Country [17] 0 0
Spain
State/province [17] 0 0
Cantabria
Country [18] 0 0
Spain
State/province [18] 0 0
Madrid
Country [19] 0 0
Sweden
State/province [19] 0 0
Uppsala
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Cambridge
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Leeds
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Thomas Bowman, MD
Address 0 0
Dicerna Pharmaceuticals / Novo Nordisk
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04764448