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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
6/11/2024

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
The incidence and nature of treatment emergent adverse events (TEAE)
Timepoint [1] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [2] 0 0
Change from baseline in pulmonary function tests (PFTs): Forced Vital Capacity (FVC)
Timepoint [2] 0 0
Time Frame: up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [3] 0 0
Change from baseline in pulmonary function tests (PFTs): Forced Expiratory Volume in One Second (FEV1)
Timepoint [3] 0 0
Time Frame: up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [4] 0 0
Change from baseline in pulmonary function tests (PFTs): Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Timepoint [4] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [5] 0 0
Change from baseline in 12-lead ECGs: Heart Rate
Timepoint [5] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [6] 0 0
Change from baseline in 12-lead ECGs: Ventricular Rate
Timepoint [6] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [7] 0 0
Change from baseline in 12-lead ECGs: RR interval
Timepoint [7] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [8] 0 0
Change from baseline in 12-lead ECGs: PR interval
Timepoint [8] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [9] 0 0
Change from baseline in 12-lead ECGs: QRS interval
Timepoint [9] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [10] 0 0
Change from baseline in 12-lead ECGs: QT interval
Timepoint [10] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [11] 0 0
Change from baseline in 12-lead ECGs: corrected QT interval
Timepoint [11] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [12] 0 0
The incidence of clinically significant physical examination (PE) findings
Timepoint [12] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [13] 0 0
Change from baseline in vital sign measurements: temperature
Timepoint [13] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [14] 0 0
Change from baseline in vital sign measurements: pulse rate
Timepoint [14] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [15] 0 0
Change from baseline in vital sign measurements: respiratory rate
Timepoint [15] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [16] 0 0
Change from baseline in vital sign measurements: blood pressure
Timepoint [16] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [17] 0 0
Change from baseline in clinical laboratory tests: clinical chemistry
Timepoint [17] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [18] 0 0
Change from baseline in clinical laboratory tests: hematology
Timepoint [18] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [19] 0 0
Change from baseline in clinical laboratory tests: Coagulation
Timepoint [19] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [20] 0 0
Change from baseline in clinical laboratory tests: Serum AFP
Timepoint [20] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [21] 0 0
Change from baseline in clinical laboratory tests: Total complement hemolytic activity CH50
Timepoint [21] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [22] 0 0
Change from baseline in clinical laboratory tests: C-reactive protein (CRP)
Timepoint [22] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [23] 0 0
Change from baseline in clinical laboratory tests: Antidrug antibodies
Timepoint [23] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [24] 0 0
Change from Baseline in serum AAT concentration
Timepoint [24] 0 0
up to 24 weeks (Cohort 1), up to 48 weeks (Cohort 2)
Primary outcome [25] 0 0
Change from baseline to Week 24 in serum Z-AAT protein levels
Timepoint [25] 0 0
up to 24 weeks (Cohort 3)
Primary outcome [26] 0 0
Change from baseline to Week 24 in liver Z-AAT liver protein levels
Timepoint [26] 0 0
up to 24 weeks (Cohort 3)

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
This is a multiple dose, randomized, placebo-controlled, double-blind study of belcesiran to evaluate the safety, tolerability, PK, and PD in adult patients with PiZZ AATD-associated liver disease (AATLD).

The study will be conducted in 3 separate cohorts. A total of up to 16 participants may be enrolled in Cohort 1 and 2. A total number of 30 subjects will be enrolled in cohort 3. The 3 cohorts are differentiated by the duration of the treatment period, the number of doses administered, and the timing of the second liver biopsy.
Trial website
https://clinicaltrials.gov/study/NCT04764448
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04764448