A Study of Belcesiran in Patients With AATLD | NCT04764448

Label	Type	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Belcesiran	Drug	Administered multiple fixed doses of belcesiran by subcutaneous (sc) injection for 24 weeks. Extension offered to participants.	Belcesiran Cohort 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.

Secondary Outcomes

Measure	Description	Time Frame
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.

Name	Affiliation	Role
Thomas Bowman, MD	Dicerna Pharmaceuticals / Novo Nordisk	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of California - San Diego		La Jolla	California	92093	United States
University of Florida

ID	Title	Description
FG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 2, 2023	Dec 6, 2024

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of belcesiran/placebo.

Posted

Number

Events

Up to 2.6 years

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Units	Counts
Participants	OG0005 OG0015 OG0026

Title

Denominators

Categories

TEAE

Title	Measurements
	OG00027 OG00180 OG00243

SAE

Primary

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.

Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of belcesiran/placebo.

Posted

Count of Participants

Participants

Up to 2.6 years

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.

Primary

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.

Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of belcesiran/placebo. Overall number of participants analyzed = Participants with available data for the outcome measure.

Posted

Mean

Standard Deviation

Liters (L)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002

Primary

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.

Posted

Mean

Standard Deviation

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

Ratio of FEV1/FVC

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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).

Posted

Mean

Standard Deviation

mmol/min/kPa

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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.

Posted

Mean

Standard Deviation

beats per minute

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in 12 -Lead ECGs: Mean Ventricular Rate

Change from baseline (Day 1) to week 96 in mean ventricular rate is presented.

Posted

Mean

Standard Deviation

beats per minute

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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.

Posted

Mean

Standard Deviation

millisecond (msec)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002

Primary

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.

Posted

Count of Participants

Participants

At week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

millimeters of mercury (mmHg)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Vital Signs: Heart Rate

Change from baseline (Day 1) to week 96 in heart rate is presented.

Posted

Mean

Standard Deviation

beats per minute

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Vital Signs: Height at Baseline

Height at baseline is presented.

Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of belcesiran/placebo.

Posted

Mean

Standard Deviation

Centimeter (cm)

Baseline (Day 1)

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Vital Signs: Respiratory Rate

Change from baseline (Day 1) to week 96 in respiratory rate is presented.

Posted

Mean

Standard Deviation

breaths per minute

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Vital Signs: Temperature

Change from baseline (Day 1) to week 96 in temperature is presented.

Posted

Mean

Standard Deviation

Degree celsius

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Vital Signs: Weight

Change from baseline (Day 1) to week 96 in weight is presented.

Posted

Mean

Standard Deviation

kilograms (kg)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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.

Posted

Mean

Standard Deviation

Units per liter (U/L)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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.

Posted

Mean

Standard Deviation

Grams per liter (g/L)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002

Primary

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.

Posted

Mean

Standard Deviation

Micromoles per liter (umol/L)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

Millimoles per liter (mmol/L)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Gamma Glutamyl Transferase

Change from baseline (Day 1) to week 96 in gamma glutamyl transferase is presented.

Posted

Mean

Standard Deviation

International units per liter (IU/L)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

10^9 cells/liter

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Basophils/Leucocytes

Change from baseline (Day 1) to week 96 in basophils/leucocytes is presented.

Posted

Mean

Standard Deviation

Percentage of basophils/leucocytes

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Eosinophils/Leucocytes

Change from baseline (Day 1) to week 96 in eosinophils/leucocytes is presented.

Posted

Mean

Standard Deviation

Percentage of eosinophils/leucocytes

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Haematocrit

Change from baseline (Day 1) to week 96 in haematocrit is presented.

Posted

Mean

Standard Deviation

Percentage of haematocrit

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Clinical Laboratory Tests: Lymphocytes/Leucocytes

Change from baseline (Day 1) to week 96 in lymphocytes/leucocytes is presented.

Posted

Mean

Standard Deviation

Percentage of lymphocytes/leucocytes

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Monocytes/Leucocytes

Change from baseline (Day 1) to week 96 in monocytes/leucocytes is presented.

Posted

Mean

Standard Deviation

Percentage of monocytes/leucocytes

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Neutrophils/Leucocytes

Change from baseline (Day 1) to week 96 in neutrophils/leucocytes is presented.

Posted

Mean

Standard Deviation

Percentage of neutrophils/leucocytes

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Reticulocytes/Erythrocytes

Change from baseline (Day 1) to week 96 in reticulocytes/erythrocytes is presented.

Posted

Mean

Standard Deviation

Percentage of reticulocytes/erythrocytes

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

g/L

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

picograms (pg)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

femtoliter (fL)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Erythrocytes

Change from baseline (Day 1) to week 96 in erythrocytes is presented.

Posted

Mean

Standard Deviation

10^12 cells/liter

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Clinical Laboratory Tests: Specific Gravity

Change from baseline (Day 1) to week 96 in specific gravity is reported.

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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.

Posted

Mean

Standard Deviation

per high power field (/HPF)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

Change From Baseline in Clinical Laboratory Tests: Potential of Hydrogen (pH)

Change from baseline (Day 1) to week 96 in pH is presented.

Posted

Mean

Standard Deviation

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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.

Posted

Mean

Standard Deviation

seconds (sec)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of belcesiran/placebo. Overall number of participants analyzed= Participants with available data for the outcome measure.

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran

Primary

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.

Posted

Mean

Standard Deviation

nanograms per milliter (ng/mL)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Clinical Laboratory Tests: C-Reactive Protein

Change from baseline (Day 1) to week 96 in C-reactive protein is presented.

Posted

Mean

Standard Deviation

mg/L

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Clinical Laboratory Tests: Complement Bb

Change from baseline (Day 1) to week 96 in complement Bb is presented.

Posted

Mean

Standard Deviation

microgram per milliliter (ug/mL)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

Change From Baseline in Clinical Laboratory Tests: Complement Total (CH50)

Change from baseline (Day 1) to week 96 in CH50 is presented.

Posted

Mean

Standard Deviation

equivalent unit per milliliter (U Eq/mL)

Baseline (Day 1), week 96

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
OG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
OG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Primary

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.

Pharmacodynamic (PD) population included all participants randomly assigned to study intervention who received at least 1 dose of belcesiran (or placebo) and at least 1 postdose PD assessment. Overall number of participants analyzed = Participants with available data for the outcome measure.

Posted

Mean

Standard Deviation

g/L

Baseline (Day 1), week 24

ID	Title	Description
OG000	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.

Units	Counts
Participants	OG000

Primary

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.

PD population included all participants randomly assigned to study intervention who received at least 1 dose of belcesiran (or placebo) and at least 1 postdose PD assessment. Overall number of participants analyzed = Participants with available data for the outcome measure.

Posted

Mean

Standard Deviation

g/L

Baseline (Day 1), week 48

ID	Title	Description
OG000	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.

Units	Counts
Participants	OG000

Secondary

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.

Safety population included all participants randomly assigned to study intervention and who received at least 1 dose of belcesiran/placebo. Overall number of participants analyzed= Participants with available data for the outcome measure.

Posted

Mean

Standard Deviation

unit on a score

Baseline (Day 1), week 48

ID	Title	Description
OG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
COVID-19	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0022 events2 affected6 at risk
Upper respiratory tract infection	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0022 events2 affected6 at risk
Bronchitis	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0021 events1 affected6 at risk
Pneumonia	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected5 at risk EG0020 events0 affected6 at risk
Asymptomatic bacteriuria	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Cystitis	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Erysipelas	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Laryngitis	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Mycobacterium avium complex infection	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Nasopharyngitis	Infections and infestations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0022 events1 affected6 at risk
Parainfluenzae virus infection	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Respiratory tract infection	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Rhinovirus infection	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Chronic sinusitis	Infections and infestations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Paronychia	Infections and infestations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Tinea pedis	Infections and infestations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Crystal urine present	Investigations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0012 events2 affected5 at risk EG0020 events0 affected6 at risk
Hyaluronic acid increased	Investigations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected5 at risk EG0021 events1 affected6 at risk
Pulmonary function test decreased	Investigations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Blood glucose increased	Investigations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0012 events1 affected5 at risk EG0020 events0 affected6 at risk
Complement factor C4 increased	Investigations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Enzyme level increased	Investigations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected5 at risk EG0020 events0 affected6 at risk
Faecal volume increased	Investigations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Forced expiratory volume decreased	Investigations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Lung diffusion test decreased	Investigations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Serum procollagen type III N-terminal propeptide increased	Investigations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Alpha-2 macroglobulin increased	Investigations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Blood bilirubin increased	Investigations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Blood creatine phosphokinase increased	Investigations	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Asthenia	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Chest discomfort	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Chills	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Early satiety	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Fatigue	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Feeling abnormal	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Injection site bruising	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Injection site discoloration	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Injection site erythema	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0025 events1 affected6 at risk
Injection site pain	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Oedema peripheral	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Pyrexia	General disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Catheter site bruise	General disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Cough	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0013 events1 affected5 at risk EG0022 events2 affected6 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected5 at risk EG0020 events0 affected6 at risk
Rales	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Sputum discolored	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Arthritis	Musculoskeletal and connective tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0021 events1 affected6 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected5 at risk EG0021 events1 affected6 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Myalgia	Musculoskeletal and connective tissue disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Thrombocytopenia	Blood and lymphatic system disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0022 events2 affected6 at risk
Anemia	Blood and lymphatic system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Palpitations	Cardiac disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Abdominal pain	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0021 events1 affected6 at risk
Diarrhea	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected5 at risk EG0021 events1 affected6 at risk
Varices esophageal	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0021 events1 affected6 at risk
Ascites	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Constipation	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Toothache	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Umbilical hernia	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Vomiting	Gastrointestinal disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0012 events1 affected5 at risk EG0020 events0 affected6 at risk
Abdominal pain upper	Gastrointestinal disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Colitis	Gastrointestinal disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Gastrointestinal disorder	Gastrointestinal disorders	27.0	Systematic Assessment	EG0002 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Alopecia	Skin and subcutaneous tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Pruritus	Skin and subcutaneous tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Rash	Skin and subcutaneous tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Skin irritation	Skin and subcutaneous tissue disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Ligament sprain	Injury, poisoning and procedural complications	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Procedural pain	Injury, poisoning and procedural complications	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Soft tissue injury	Injury, poisoning and procedural complications	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Foot fracture	Injury, poisoning and procedural complications	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Skin abrasion	Injury, poisoning and procedural complications	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Diabetes mellitus	Metabolism and nutrition disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Gout	Metabolism and nutrition disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Hypoglycemia	Metabolism and nutrition disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Headache	Nervous system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0013 events2 affected5 at risk EG0020 events0 affected6 at risk
Balance disorder	Nervous system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Iron deficiency	Metabolism and nutrition disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Head discomfort	Nervous system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Memory impairment	Nervous system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Tremor	Nervous system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Tinnitus	Ear and labyrinth disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Hepatic cirrhosis	Hepatobiliary disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Hepatic lesion	Hepatobiliary disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Drug hypersensitivity	Immune system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Confusional state	Psychiatric disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Depression	Psychiatric disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Urinary incontinence	Renal and urinary disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Glycosuria	Renal and urinary disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk
Proteinuria	Renal and urinary disorders	27.0	Systematic Assessment	EG0001 events1 affected5 at risk EG0010 events0 affected5 at risk EG0020 events0 affected6 at risk

ID	Term
D008107	Liver Diseases
D004066	Digestive System Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D013352	Subcutaneous Emphysema
D004646	Emphysema
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description
BG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.
BG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.
BG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pooled Placebo	All participants in cohort 1 and 2 received belcesiran matched placebo as subcutaneous injection, in Cohort 1 participants received monthly dosing for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96 and in Cohort 2 participants received monthly dosing for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96. Due to study termination participants were followed up to 2 months.	5	0	5	5	5
EG001	Cohort 1: Belcesiran	Participants received a fixed dose of belcesiran 210 milligrams (mg) injection monthly for the first 24 weeks and then shifted to quarterly dosing thereafter until week 96.	5	2	5	5	5
EG002	Cohort 2: Belcesiran	Participants received a fixed dose of belcesiran 210 mg injection subcutaneously monthly for the first 48 weeks and then shifted to quarterly dosing thereafter until week 96.	6	2	6	5	6

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Atrial fibrillation	Cardiac disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Erysipelas	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Pneumonia	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0013 events1 affected5 at risk EG0020 events0 affected6 at risk
Viral infection	Infections and infestations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Hepatic function abnormal	Hepatobiliary disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Pulmonary function test decreased	Investigations	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0010 events0 affected5 at risk EG0021 events1 affected6 at risk
Hyperglycaemia	Metabolism and nutrition disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Hepatic encephalopathy	Nervous system disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk
Depression	Psychiatric disorders	27.0	Systematic Assessment	EG0000 events0 affected5 at risk EG0011 events1 affected5 at risk EG0020 events0 affected6 at risk