Alpha 1-Antitrypsin DeficiencyPhase 2ESTRELLANCT04764448
A Study of Belcesiran in Patients With AATLD
A Phase 2 study testing Belcesiran in people with Alpha 1-Antitrypsin Deficiency, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 23 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Alpha 1-Antitrypsin Deficiency
- What is being tested?
- Belcesiran
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 23 sitesin 14 countries
- Study dates
- 12 Feb 2021to 29 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
23 sites in 14 countries.
23 sites in 14 countries
United States3 sites
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Florida
Gainesville, Florida, 32611
University of California - San Diego
La Jolla, California, 92093
Portugal3 sites
Hospital da Senhora da Oliveira - Guimaraes
Creixomil
Centro Hospitalar Universitario de Sao Joao
Porto
Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE
Vila Real
United Kingdom3 sites
Addenbrooke's Hospital, Cambridge University
Cambridge
Leeds Teaching Hospitals NHS Trust
Leeds
Royal Free London NHS Foundation Trust, Royal Free Hospital
London
Germany2 sites
Universitaetsklinikum Aachen, AoeR
Aachen
Universitaetsklinikum Schleswig-Holstein Campus Kiel
Kiel
New Zealand2 sites
Auckland Clinical Studies
Grafton, Auckland, 1010
Waikato Hospital
Hamilton
Spain2 sites
Hospital Universitario La Paz
Madrid
Hospital Universitario Marques de Valdecilla Santander
Santander, Cantabria
Canada1 site
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec
France1 site
CHU Bordeaux - Hopital Haut-Leveque - Centre François Magendie
Pessac
About this study
Official 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
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.
Read the detailed description
AATD-associated liver disease is a progressive condition resulting in liver fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. The lack of functional alpha-1 antitrypsin (AAT) in individuals with the PiZZ genotype, in conjunction with other precipitating factors, can lead to unchecked activity of neutrophil elastases in the alveoli; causing emphysema and chronic obstructive pulmonary disease (COPD). This loss-of-function mechanism may be addressed by use of intravenous augmentation therapy, which aims to substitute the missing AAT by infusing alpha-1 proteinase inhibitor (A1PI), purified from pooled human plasma.
While augmentation therapy can address the loss of AAT in the lung, no treatment exists for the associated liver disease.
Given the severity of the disease, with approximately 10% of affected patients developing liver cirrhosis and a subgroup of those patients in need of liver transplantation, and the lack of an effective treatment that addresses the toxic hepatic "gain-of-function" mechanism, there is an urgent unmet medical need to develop a therapy that can help this particular patient population.
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Being tested
- Belcesiran, Placebo
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BelcesiranDrug
Administered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 24 weeks. Extension offered to participants.
PlaceboOther
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.
BelcesiranDrug
Administered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 48 weeks. Extension offered to participants.
PlaceboOther
Administered sterile normal saline (0.9% NaCl) matching volumes of belcesiran by subcutaneous (sc) injection for 48 weeks. Extension offered to participants.
BelcesiranDrug
Administered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 96 weeks.
PlaceboOther
Administered sterile normal saline (0.9% NaCl) matching volumes of belcesiran by subcutaneous (sc) injection for 96 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Belcesiran Cohort 1 | Experimental | Not described Receives: Drug: Belcesiran |
| Placebo Cohort 1 | Placebo comparator | Not described Receives: Other: Placebo |
| Belcesiran Cohort 2 | Experimental | Not described Receives: Drug: Belcesiran |
| Placebo Cohort 2 | Placebo comparator | Not described Receives: Other: Placebo |
| Belcesiran Cohort 3 | Experimental | Not described Receives: Drug: Belcesiran |
| Placebo Cohort 3 | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Number of TEAEs and SAEs is presented. An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were defined as TEAEs if they had a start date on or after the administration of study drug during the treatment period, or if they occurred prior to the administration of study drug and worsened in severity/grade or relationship to the study intervention after the administration of study intervention during the treatment period. A SAE was defined as any untoward medical occurrence that, at any dose: a) resulted in death, b) is life-threatening, c) required inpatient hospitalization or prolongation of existing hospitalization, d) resulted in persistent disability/incapacity, e) was a congenital anomaly/birth defect.
Measured: Up to 2.6 years
Number of Participants With TEAEs and SAEs
Number of participants with TEAEs and SAEs is presented. An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were defined as TEAEs if they had a start date on or after the administration of study drug during the treatment period, or if they occurred prior to the administration of study drug and worsened in severity/grade or relationship to the study intervention after the administration of study intervention during the treatment period. A SAE was defined as any untoward medical occurrence that, at any dose: a) resulted in death, b) is life-threatening, c) required inpatient hospitalization or prolongation of existing hospitalization, d) resulted in persistent disability/incapacity, e) was a congenital anomaly/birth defect.
Measured: Up to 2.6 years
Change From Baseline in Pulmonary Function Tests (PFTs): Forced Vital Capacity (FVC)
Change in FVC from baseline (Day 1) to week 96 is presented. FVC is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, that is, VC performed with a maximally forced expiratory effort.
Measured: Baseline (Day 1), week 96
Change From Baseline in PFT: Forced Expiratory Volume in One Second (FEV1)
Change in FEV1 from baseline (Day 1) to week 96 is presented. FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.
Measured: Baseline (Day 1), week 96
Change From Baseline in PFT: FEV1/FVC Ratio
Change in FEV1/FVC ratio from baseline (Day 1) to week 96 is presented. FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, that is, VC performed with a maximally forced expiratory effort.
Measured: Baseline (Day 1), week 96
Change From Baseline in PFT: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Change in DLCO from baseline (Day 1) to week 96 is presented. DLCO is a measure of the quantity of carbon monoxide (CO) transferred per minute from alveolar gas to red blood cells (specifically hemoglobin) in pulmonary capillaries. It is expressed as millimoles per minute per kilopascal (mmol/min/kPa).
Measured: Baseline (Day 1), week 96
Change From Baseline in 12 -Lead Electrochardiograms (ECGs): Mean Heart Rate
Change from baseline (Day 1) to week 96 in mean heart rate is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in 12 -Lead ECGs: Mean Ventricular Rate
Change from baseline (Day 1) to week 96 in mean ventricular rate is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval
Change from baseline (Day 1) to week 96 in PR interval, QRS interval, QT interval, QTcF interval and RR interval is presented.
Measured: Baseline (Day 1), week 96
Number of Participants With Physical Examination Findings
Number of participants with physical examination findings at week 96 is presented. The data is presented under categories:a) Normal, b) Abnormal, not clinically significant, c) Abnormal, clinically significant.
Measured: At week 96
Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure
Change from baseline (Day 1) to week 96 in diastolic blood pressure and systolic blood pressure is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Vital Signs: Heart Rate
Change from baseline (Day 1) to week 96 in heart rate is presented.
Measured: Baseline (Day 1), week 96
Vital Signs: Height at Baseline
Height at baseline is presented.
Measured: Baseline (Day 1)
Change From Baseline in Vital Signs: Respiratory Rate
Change from baseline (Day 1) to week 96 in respiratory rate is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Vital Signs: Temperature
Change from baseline (Day 1) to week 96 in temperature is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Vital Signs: Weight
Change from baseline (Day 1) to week 96 in weight is presented.
Measured: 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)
Change from baseline (Day 1) to week 96 in alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatine kinase, glutamate dehydrogenase, lactate dehydrogenase, biomarker creatine kinase (M30) and biomarker creatine kinase (M65) is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin
Change from baseline (Day 1) to week 96 in albumin, apolipoprotein A1, protein and biomarker haptoglobin is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Bilirubin, Creatinine and Direct Bilirubin
Change from baseline (Day 1) to week 96 in bilirubin, creatinine and direct bilirubin is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen
Change from baseline (Day 1) to week 96 in chloride, cholesterol, glucose, potassium, sodium, triglycerides and urea nitrogen is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Gamma Glutamyl Transferase
Change from baseline (Day 1) to week 96 in gamma glutamyl transferase is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Change from baseline (Day 1) to week 96 in basophils, eosinophils, leucocytes, lymphocytes, monocytes, neutrophils and platelets is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Basophils/Leucocytes
Change from baseline (Day 1) to week 96 in basophils/leucocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Eosinophils/Leucocytes
Change from baseline (Day 1) to week 96 in eosinophils/leucocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Haematocrit
Change from baseline (Day 1) to week 96 in haematocrit is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Lymphocytes/Leucocytes
Change from baseline (Day 1) to week 96 in lymphocytes/leucocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Monocytes/Leucocytes
Change from baseline (Day 1) to week 96 in monocytes/leucocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Neutrophils/Leucocytes
Change from baseline (Day 1) to week 96 in neutrophils/leucocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Reticulocytes/Erythrocytes
Change from baseline (Day 1) to week 96 in reticulocytes/erythrocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin Concentration and Haemoglobin
Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular haemoglobin concentration and haemoglobin is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin
Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular haemoglobin is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Volume
Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular volume is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Erythrocytes
Change from baseline (Day 1) to week 96 in erythrocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Specific Gravity
Change from baseline (Day 1) to week 96 in specific gravity is reported.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Urine Erythrocytes and Urine Leucocytes
Change from baseline (Day 1) to week 96 in urine erythrocytes and urine leucocytes is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Potential of Hydrogen (pH)
Change from baseline (Day 1) to week 96 in pH is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Activated Partial Thromboplastin Time and Prothrombin Time
Change from baseline (Day 1) to week 96 in activated partial thromboplastin time and prothrombin time is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Prothrombin International Normalized Ratio
Change from baseline (Day 1) to week 96 in prothrombin international normalized ratio is presented.
Measured: 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
Change from baseline (Day 1) to week 96 in 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 is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: C-Reactive Protein
Change from baseline (Day 1) to week 96 in C-reactive protein is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Complement Bb
Change from baseline (Day 1) to week 96 in complement Bb is presented.
Measured: Baseline (Day 1), week 96
Change From Baseline in Clinical Laboratory Tests: Complement Total (CH50)
Change from baseline (Day 1) to week 96 in CH50 is presented.
Measured: Baseline (Day 1), week 96
Cohort 1: Change From Baseline in Serum Alpha-1 Antitrypsin (AAT) Protein Concentrations
Change from baseline (Day 1) to week 24 in serum AAT protein concentrations in Cohort 1 is presented.
Measured: Baseline (Day 1), week 24
Cohort 2: Change From Baseline in Serum AAT Protein Concentrations
Change from baseline (Day 1) to week 48 in serum AAT protein concentrations in Cohort 2 is presented.
Measured: Baseline (Day 1), week 48
Secondary outcomes (1)
Change From Baseline in Liver Fibrosis Ishak Score
Change from Baseline up until week 48 in liver fibrosis based on Ishak score is presented. The Ishak staging system for liver fibrosis is a 1995 update to the algorithm initially developed by De Groote et al. Ishak scores range from 0 (no fibrosis) to 6 (cirrhosis) which are as follows: 0-no fibrosis, 1-fibrous expansion of some portal areas, with or without short fibrous septa, 2-Fibrous expansion of most portal areas, with or without short fibrous septa, 3-Fibrous expansion of most portal areas with occasional portal-to-portal bridging, 4-Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to central), 5-Marked bridging (portal-portal and/or portal-central) with occasional nodules (incomplete cirrhosis), 6-Cirrhosis, probable or definite.
Measured: Baseline (Day 1), week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start12 Feb 2021
- Primary completion8 Dec 2023
- Study completion29 May 2024
Why it stopped: Development project was discontinued
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alpha 1-Antitrypsin DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Thomas Bowman, MD, Study director, Dicerna Pharmaceuticals / Novo Nordisk
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04764448
- Sponsor's protocol ID
- DCR-A1AT-201
- Acronym
- ESTRELLA
- Status last verified
- Mar 2026
- First submitted
- 27 Jan 2021
- Last updated
- 7 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04764448
- Acronym / sponsor ID
- ESTRELLA / DCR-A1AT-201
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Development project was discontinued
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk companyIndustry (pharma, biotech, devices)
- Study start
- 12 Feb 2021 (actual)
- Primary completion
- 8 Dec 2023 (actual)
- Study completion
- 29 May 2024 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Posted 31 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
AATD-associated liver disease is a progressive condition resulting in liver fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. The lack of functional alpha-1 antitrypsin (AAT) in individuals with the PiZZ genotype, in conjunction with other precipitating factors, can lead to unchecked activity of neutrophil elastases in the alveoli; causing emphysema and chronic obstructive pulmonary disease (COPD). This loss-of-function mechanism may be addressed by use of intravenous augmentation therapy, which aims to substitute the missing AAT by infusing alpha-1 proteinase inhibitor (A1PI), purified from pooled human plasma.
While augmentation therapy can address the loss of AAT in the lung, no treatment exists for the associated liver disease.
Given the severity of the disease, with approximately 10% of affected patients developing liver cirrhosis and a subgroup of those patients in need of liver transplantation, and the lack of an effective treatment that addresses the toxic hepatic "gain-of-function" mechanism, there is an urgent unmet medical need to develop a therapy that can help this particular patient population.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Belcesiran Cohort 1 | Experimental | Drug: Belcesiran |
| Placebo Cohort 1 | Placebo comparator | Other: Placebo |
| Belcesiran Cohort 2 | Experimental | Drug: Belcesiran |
| Placebo Cohort 2 | Placebo comparator | Other: Placebo |
| Belcesiran Cohort 3 | Experimental | Drug: Belcesiran |
| Placebo Cohort 3 | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BelcesiranAdministered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 24 weeks. Extension offered to participants. | Drug | Belcesiran Cohort 1 |
| PlaceboComparator: 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. | Other | Placebo Cohort 1 |
| BelcesiranAdministered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 48 weeks. Extension offered to participants. | Drug | Belcesiran Cohort 2 |
| PlaceboAdministered sterile normal saline (0.9% NaCl) matching volumes of belcesiran by subcutaneous (sc) injection for 48 weeks. Extension offered to participants. | Other | Placebo Cohort 2 |
| BelcesiranAdministered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 96 weeks. | Drug | Belcesiran Cohort 3 |
| PlaceboAdministered sterile normal saline (0.9% NaCl) matching volumes of belcesiran by subcutaneous (sc) injection for 96 weeks. | Other | Placebo Cohort 3 |
Primary outcome
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 2.6 years
Number of TEAEs and SAEs is presented. An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were defined as TEAEs if they had a start date on or after the administration of study drug during the treatment period, or if they occurred prior to the administration of study drug and worsened in severity/grade or relationship to the study intervention after the administration of study intervention during the treatment period. A SAE was defined as any untoward medical occurrence that, at any dose: a) resulted in death, b) is life-threatening, c) required inpatient hospitalization or prolongation of existing hospitalization, d) resulted in persistent disability/incapacity, e) was a congenital anomaly/birth defect.
Number of Participants With TEAEs and SAEs
Time frame: Up to 2.6 years
Number of participants with TEAEs and SAEs is presented. An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs were defined as TEAEs if they had a start date on or after the administration of study drug during the treatment period, or if they occurred prior to the administration of study drug and worsened in severity/grade or relationship to the study intervention after the administration of study intervention during the treatment period. A SAE was defined as any untoward medical occurrence that, at any dose: a) resulted in death, b) is life-threatening, c) required inpatient hospitalization or prolongation of existing hospitalization, d) resulted in persistent disability/incapacity, e) was a congenital anomaly/birth defect.
Change From Baseline in Pulmonary Function Tests (PFTs): Forced Vital Capacity (FVC)
Time frame: Baseline (Day 1), week 96
Change in FVC from baseline (Day 1) to week 96 is presented. FVC is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, that is, VC performed with a maximally forced expiratory effort.
Change From Baseline in PFT: Forced Expiratory Volume in One Second (FEV1)
Time frame: Baseline (Day 1), week 96
Change in FEV1 from baseline (Day 1) to week 96 is presented. FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.
Change From Baseline in PFT: FEV1/FVC Ratio
Time frame: Baseline (Day 1), week 96
Change in FEV1/FVC ratio from baseline (Day 1) to week 96 is presented. FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, that is, VC performed with a maximally forced expiratory effort.
Change From Baseline in PFT: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Time frame: Baseline (Day 1), week 96
Change in DLCO from baseline (Day 1) to week 96 is presented. DLCO is a measure of the quantity of carbon monoxide (CO) transferred per minute from alveolar gas to red blood cells (specifically hemoglobin) in pulmonary capillaries. It is expressed as millimoles per minute per kilopascal (mmol/min/kPa).
Change From Baseline in 12 -Lead Electrochardiograms (ECGs): Mean Heart Rate
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in mean heart rate is presented.
Change From Baseline in 12 -Lead ECGs: Mean Ventricular Rate
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in mean ventricular rate is presented.
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 (Day 1) to week 96 in PR interval, QRS interval, QT interval, QTcF interval and RR interval is presented.
Number of Participants With Physical Examination Findings
Time frame: At week 96
Number of participants with physical examination findings at week 96 is presented. The data is presented under categories:a) Normal, b) Abnormal, not clinically significant, c) Abnormal, clinically significant.
Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in diastolic blood pressure and systolic blood pressure is presented.
Change From Baseline in Vital Signs: Heart Rate
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in heart rate is presented.
Vital Signs: Height at Baseline
Time frame: Baseline (Day 1)
Height at baseline is presented.
Change From Baseline in Vital Signs: Respiratory Rate
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in respiratory rate is presented.
Change From Baseline in Vital Signs: Temperature
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in temperature is presented.
Change From Baseline in Vital Signs: Weight
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in weight is presented.
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 (Day 1) to week 96 in alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatine kinase, glutamate dehydrogenase, lactate dehydrogenase, biomarker creatine kinase (M30) and biomarker creatine kinase (M65) is presented.
Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in albumin, apolipoprotein A1, protein and biomarker haptoglobin is presented.
Change From Baseline in Clinical Laboratory Tests: Bilirubin, Creatinine and Direct Bilirubin
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in bilirubin, creatinine and direct bilirubin is presented.
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 (Day 1) to week 96 in chloride, cholesterol, glucose, potassium, sodium, triglycerides and urea nitrogen is presented.
Change From Baseline in Clinical Laboratory Tests: Gamma Glutamyl Transferase
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in gamma glutamyl transferase is presented.
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 (Day 1) to week 96 in basophils, eosinophils, leucocytes, lymphocytes, monocytes, neutrophils and platelets is presented.
Change From Baseline in Clinical Laboratory Tests: Basophils/Leucocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in basophils/leucocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Eosinophils/Leucocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in eosinophils/leucocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Haematocrit
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in haematocrit is presented.
Change From Baseline in Clinical Laboratory Tests: Lymphocytes/Leucocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in lymphocytes/leucocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Monocytes/Leucocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in monocytes/leucocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Neutrophils/Leucocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in neutrophils/leucocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Reticulocytes/Erythrocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in reticulocytes/erythrocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin Concentration and Haemoglobin
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular haemoglobin concentration and haemoglobin is presented.
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular haemoglobin is presented.
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Volume
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular volume is presented.
Change From Baseline in Clinical Laboratory Tests: Erythrocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in erythrocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Specific Gravity
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in specific gravity is reported.
Change From Baseline in Clinical Laboratory Tests: Urine Erythrocytes and Urine Leucocytes
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in urine erythrocytes and urine leucocytes is presented.
Change From Baseline in Clinical Laboratory Tests: Potential of Hydrogen (pH)
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in pH is presented.
Change From Baseline in Clinical Laboratory Tests: Activated Partial Thromboplastin Time and Prothrombin Time
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in activated partial thromboplastin time and prothrombin time is presented.
Change From Baseline in Clinical Laboratory Tests: Prothrombin International Normalized Ratio
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in prothrombin international normalized ratio is presented.
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 (Day 1) to week 96 in 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 is presented.
Change From Baseline in Clinical Laboratory Tests: C-Reactive Protein
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in C-reactive protein is presented.
Change From Baseline in Clinical Laboratory Tests: Complement Bb
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in complement Bb is presented.
Change From Baseline in Clinical Laboratory Tests: Complement Total (CH50)
Time frame: Baseline (Day 1), week 96
Change from baseline (Day 1) to week 96 in CH50 is presented.
Cohort 1: Change From Baseline in Serum Alpha-1 Antitrypsin (AAT) Protein Concentrations
Time frame: Baseline (Day 1), week 24
Change from baseline (Day 1) to week 24 in serum AAT protein concentrations in Cohort 1 is presented.
Cohort 2: Change From Baseline in Serum AAT Protein Concentrations
Time frame: Baseline (Day 1), week 48
Change from baseline (Day 1) to week 48 in serum AAT protein concentrations in Cohort 2 is presented.
1 secondary outcome
Change From Baseline in Liver Fibrosis Ishak Score
Time frame: Baseline (Day 1), week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Bowman, MD study director
Dicerna Pharmaceuticals / Novo Nordisk
23 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Belcesiran in people with Alpha 1-Antitrypsin Deficiency, run by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company at 23 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Portugal, United Kingdom, Germany, New Zealand and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Up to 2.6 years). The study lists 44 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2026.