A Study of Belcesiran in Patients With AATLD

• Register: ClinicalTrials.gov
• Last refreshed on: 6 January 2025
• Main ID: NCT04764448
• Date of registration: 27/01/2021
• Prospective Registration: Yes
• Primary sponsor: Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
• Public title: A Study of Belcesiran in Patients With AATLD ESTRELLA
• 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
• Date of first enrolment: February 12, 2021
• Target sample size: 16
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT04764448
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Australia, Austria, Belgium, Canada, France, Germany, Ireland, Netherlands, New Zealand, Portugal, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Thomas Bowman, MD
• Affiliation: Dicerna Pharmaceuticals / Novo Nordisk

Key inclusion & exclusion criteria

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.

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.


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alpha 1-Antitrypsin Deficiency

Intervention(s)

Other: Placebo

Drug: Belcesiran

Primary Outcome(s)

Change From Baseline in PFT: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in 12 -Lead ECGs: Mean Ventricular Rate [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in 12 -Lead Electrochardiograms (ECGs): Mean Heart Rate [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Activated Partial Thromboplastin Time and Prothrombin Time [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Eosinophils/Leucocytes [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Bilirubin, Creatinine and Direct Bilirubin [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Lymphocytes/Leucocytes [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: C-Reactive Protein [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Basophils/Leucocytes [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Complement Total (CH50) [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Gamma Glutamyl Transferase [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Volume [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin Concentration and Haemoglobin [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Pulmonary Function Tests (PFTs): Forced Vital Capacity (FVC) [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Monocytes/Leucocytes [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Vital Signs: Weight [Time Frame: Baseline (Day 1), week 96]

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 [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Neutrophils/Leucocytes [Time Frame: Baseline (Day 1), week 96]

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) [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Specific Gravity [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Erythrocytes [Time Frame: Baseline (Day 1), week 96]

Number of Participants With Physical Examination Findings [Time Frame: At week 96]

Change From Baseline in Clinical Laboratory Tests: Haematocrit [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Vital Signs: Temperature [Time Frame: Baseline (Day 1), week 96]

Cohort 2: Change From Baseline in Serum AAT Protein Concentrations [Time Frame: Baseline (Day 1), week 48]

Change From Baseline in Clinical Laboratory Tests: Urine Erythrocytes and Urine Leucocytes [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Prothrombin International Normalized Ratio [Time Frame: Baseline (Day 1), week 96]

Cohort 1: Change From Baseline in Serum Alpha-1 Antitrypsin (AAT) Protein Concentrations [Time Frame: Baseline (Day 1), week 24]

Change From Baseline in PFT: Forced Expiratory Volume in One Second (FEV1) [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Vital Signs: Respiratory Rate [Time Frame: Baseline (Day 1), week 96]

Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time Frame: Up to 2.6 years]

Number of Participants With TEAEs and SAEs [Time Frame: Up to 2.6 years]

Vital Signs: Height at Baseline [Time Frame: Baseline (Day 1)]

Change From Baseline in Clinical Laboratory Tests: Complement Bb [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Potential of Hydrogen (pH) [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Clinical Laboratory Tests: Reticulocytes/Erythrocytes [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in PFT: FEV1/FVC Ratio [Time Frame: Baseline (Day 1), week 96]

Change From Baseline in Vital Signs: Heart Rate [Time Frame: Baseline (Day 1), week 96]

Secondary Outcome(s)

Change From Baseline in Liver Fibrosis Ishak Score [Time Frame: Baseline (Day 1), week 48]

Secondary ID(s)

DCR-A1AT-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 31/12/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT04764448