Trial Outcomes & Findings for A Study of Belcesiran in Patients With AATLD (NCT NCT04764448)

Last Updated: 2024-12-31

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Up to 2.6 years

Results posted on

2024-12-31

Participant Flow

The trial was conducted at 8 sites in 8 countries. The number of sites that randomised participants are as follows: Australia (1), Belgium (1), Germany (1), Netherlands (1), New zealand (1), Portugal (1), Spain (1) and United states of America (1).

The study was planned to be conducted in 3 separate cohorts: cohort 1, 2 and 3 however, due to early termination of the study, cohort 3 was not enrolled. Participants were randomized in a 1:1 fashion to either Cohort 1 or 2. In each cohort participants were further randomized to receive either Belcesiran or placebo. Randomization was stratified based on fibrosis stage (METAVIR Score F1, F2, F3, or F4) in both cohorts 1 and 2

Participant milestones

Participant milestones
Measure	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.	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.	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.
Overall Study STARTED	5	5	6
Overall Study Safety Population	5	5	6
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	5	5	6

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	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.
Overall Study Study terminated by sponsor	2	2	5
Overall Study Withdrawal by Subject	3	3	1

Baseline Characteristics

A Study of Belcesiran in Patients With AATLD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pooled Placebo n=5 Participants 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.	Cohort 1: Belcesiran n=5 Participants 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.	Cohort 2: Belcesiran n=6 Participants 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.	Total n=16 Participants Total of all reporting groups
Age, Continuous	40.2 Years STANDARD_DEVIATION 17.31 • n=5 Participants	57.2 Years STANDARD_DEVIATION 10.18 • n=7 Participants	52.5 Years STANDARD_DEVIATION 11.86 • n=5 Participants	50.1 Years STANDARD_DEVIATION 14.36 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 2.6 years

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=5 Participants 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.	Cohort 1: Belcesiran n=5 Participants 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.	Cohort 2: Belcesiran n=6 Participants 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.
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAE	27 Events	80 Events	43 Events
Number of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAE	0 Events	7 Events	5 Events

PRIMARY outcome

Timeframe: Up to 2.6 years

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

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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=5 Participants 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.	Cohort 1: Belcesiran n=5 Participants 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.	Cohort 2: Belcesiran n=6 Participants 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.
Number of Participants With TEAEs and SAEs SAE	0 Participants	2 Participants	2 Participants
Number of Participants With TEAEs and SAEs TEAE	5 Participants	5 Participants	5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Pulmonary Function Tests (PFTs): Forced Vital Capacity (FVC)	-0.410 Liters (L)	-0.250 Liters (L) Standard Deviation 0.0424	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in PFT: Forced Expiratory Volume in One Second (FEV1)	-0.210 L	-0.290 L Standard Deviation 0.2263	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in PFT: FEV1/FVC Ratio	0.020 Ratio of FEV1/FVC	-0.055 Ratio of FEV1/FVC Standard Deviation 0.0778	—

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in PFT: Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)	-1.89497 mmol/min/kPa	-1.01110 mmol/min/kPa Standard Deviation 0.146774	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in 12 -Lead Electrochardiograms (ECGs): Mean Heart Rate	-10.0 beats per minute	1.0 beats per minute	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in 12 -Lead ECGs: Mean Ventricular Rate	-10.0 beats per minute	1.0 beats per minute	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval PR interval	-4.0 millisecond (msec)	—	—
Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval QRS interval	10.0 millisecond (msec)	21.0 millisecond (msec)	—
Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval QT interval	26.0 millisecond (msec)	17.0 millisecond (msec)	—
Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval QTcF interval	-1.0 millisecond (msec)	21.0 millisecond (msec)	—
Change From Baseline in 12 -Lead ECGs: PR Interval, QRS Interval, QT Interval, QTcF Interval and RR Interval RR interval	224.0 millisecond (msec)	-8.0 millisecond (msec)	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Number of Participants With Physical Examination Findings Normal	1 Participants	1 Participants	0 Participants
Number of Participants With Physical Examination Findings Abnormal, not clinically significant	0 Participants	1 Participants	0 Participants
Number of Participants With Physical Examination Findings Abnormal, clinically significant	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in diastolic blood pressure and systolic blood pressure is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure Diastolic blood pressure	2.0 millimeters of mercury (mmHg)	17.0 millimeters of mercury (mmHg)	—
Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure Systolic blood pressure	13.0 millimeters of mercury (mmHg)	5.0 millimeters of mercury (mmHg)	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in Vital Signs: Heart Rate	1.0 beats per minute	21.0 beats per minute	—

PRIMARY outcome

Timeframe: Baseline (Day 1)

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

Height at baseline is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=5 Participants 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.	Cohort 1: Belcesiran n=5 Participants 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.	Cohort 2: Belcesiran n=6 Participants 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.
Vital Signs: Height at Baseline	178.0 Centimeter (cm) Standard Deviation 11.07	167.8 Centimeter (cm) Standard Deviation 9.93	173.0 Centimeter (cm) Standard Deviation 13.48

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in Vital Signs: Respiratory Rate	5.0 breaths per minute	1.0 breaths per minute	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in Vital Signs: Temperature	0.30 Degree celsius	-0.40 Degree celsius	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in Vital Signs: Weight	10.70 kilograms (kg)	0.20 kilograms (kg)	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
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) Alanine aminotransferase	-8.0 Units per liter (U/L)	-10.5 Units per liter (U/L) Standard Deviation 7.78	—
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) Alkaline phosphatase	26.0 Units per liter (U/L)	0.0 Units per liter (U/L) Standard Deviation 29.70	—
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) Aspartate aminotransferase	-5.0 Units per liter (U/L)	-10.5 Units per liter (U/L) Standard Deviation 6.36	—
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) Creatine kinase	-226.0 Units per liter (U/L)	-3.0 Units per liter (U/L) Standard Deviation 8.49	—
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) Glutamate dehydrogenase	0.0 Units per liter (U/L)	-4.5 Units per liter (U/L) Standard Deviation 0.71	—
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) Lactate dehydrogenase	—	0.5 Units per liter (U/L) Standard Deviation 19.09	—
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) Biomarker creatine Kinase (M30)	—	-149.5 Units per liter (U/L) Standard Deviation 210.01	—
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) Biomarker creatine kinase (M65)	—	-166.180 Units per liter (U/L) Standard Deviation 329.3703	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in albumin, apolipoprotein A1, protein and biomarker haptoglobin is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin Albumin	-1.0 Grams per liter (g/L)	3.5 Grams per liter (g/L) Standard Deviation 0.71	—
Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin Apolipoprotein A1	-0.030 Grams per liter (g/L)	0.180 Grams per liter (g/L) Standard Deviation 0.1838	—
Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin Protein	-2.0 Grams per liter (g/L)	7.5 Grams per liter (g/L) Standard Deviation 7.78	—
Change From Baseline in Clinical Laboratory Tests: Albumin, Apolipoprotein A1, Protein, Biomarker Haptoglobin Biomarker haptoglobin	—	-0.260 Grams per liter (g/L)	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in bilirubin, creatinine and direct bilirubin is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Bilirubin, Creatinine and Direct Bilirubin Bilirubin	1.710 Micromoles per liter (umol/L)	3.420 Micromoles per liter (umol/L) Standard Deviation 0.0000	—
Change From Baseline in Clinical Laboratory Tests: Bilirubin, Creatinine and Direct Bilirubin Creatinine	1.7680 Micromoles per liter (umol/L)	22.5420 Micromoles per liter (umol/L) Standard Deviation 19.37755	—
Change From Baseline in Clinical Laboratory Tests: Bilirubin, Creatinine and Direct Bilirubin Direct bilirubin	0.000 Micromoles per liter (umol/L)	0.000 Micromoles per liter (umol/L) Standard Deviation 0.000	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen Chloride	-2.0 Millimoles per liter (mmol/L)	-1.5 Millimoles per liter (mmol/L) Standard Deviation 6.36	—
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen Cholesterol	-0.12950 Millimoles per liter (mmol/L)	0.67340 Millimoles per liter (mmol/L) Standard Deviation 0.842447	—
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen Glucose	0.88800 Millimoles per liter (mmol/L)	0.55500 Millimoles per liter (mmol/L) Standard Deviation 0.078489	—
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen Potassium	-0.60 Millimoles per liter (mmol/L)	0.40 Millimoles per liter (mmol/L) Standard Deviation 0.283	—
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen Sodium	-2.0 Millimoles per liter (mmol/L)	-0.5 Millimoles per liter (mmol/L) Standard Deviation 0.71	—
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen Triglycerides	-0.01130 Millimoles per liter (mmol/L)	0.44070 Millimoles per liter (mmol/L) Standard Deviation 0.399515	—
Change From Baseline in Clinical Laboratory Tests: Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglycerides and Urea Nitrogen Urea nitrogen	0.0000 Millimoles per liter (mmol/L)	2.4990 Millimoles per liter (mmol/L) Standard Deviation 1.00975	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Gamma Glutamyl Transferase	-5.0 International units per liter (IU/L)	-30.5 International units per liter (IU/L) Standard Deviation 24.75	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in basophils, eosinophils, leucocytes, lymphocytes, monocytes, neutrophils and platelets is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Basophils	-0.020 10^9 cells/liter	0.000 10^9 cells/liter Standard Deviation 0.0141	—
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Eosinophils	-0.030 10^9 cells/liter	-0.020 10^9 cells/liter Standard Deviation 0.0424	—
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Leucocytes	-1.650 10^9 cells/liter	-0.600 10^9 cells/liter Standard Deviation 1.1455	—
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Lymphocytes	0.310 10^9 cells/liter	-0.130 10^9 cells/liter Standard Deviation 0.0849	—
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Monocytes	-0.010 10^9 cells/liter	-0.055 10^9 cells/liter Standard Deviation 0.4738	—
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Neutrophils	-1.910 10^9 cells/liter	-0.380 10^9 cells/liter Standard Deviation 0.5657	—
Change From Baseline in Clinical Laboratory Tests: Basophils, Eosinophils, Leucocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Platelets	-39.0 10^9 cells/liter	1.0 10^9 cells/liter Standard Deviation 16.97	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Basophils/Leucocytes	-0.10 Percentage of basophils/leucocytes	0.10 Percentage of basophils/leucocytes Standard Deviation 0.424	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Eosinophils/Leucocytes	0.20 Percentage of eosinophils/leucocytes	-0.05 Percentage of eosinophils/leucocytes Standard Deviation 0.212	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Haematocrit	0.0 Percentage of haematocrit	2.5 Percentage of haematocrit Standard Deviation 2.12	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Lymphocytes/Leucocytes	17.30 Percentage of lymphocytes/leucocytes	0.85 Percentage of lymphocytes/leucocytes Standard Deviation 4.031	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Monocytes/Leucocytes	1.20 Percentage of monocytes/leucocytes	-0.50 Percentage of monocytes/leucocytes Standard Deviation 6.081	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Neutrophils/Leucocytes	-18.70 Percentage of neutrophils/leucocytes	-0.40 Percentage of neutrophils/leucocytes Standard Deviation 1.838	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Reticulocytes/Erythrocytes	-0.80 Percentage of reticulocytes/erythrocytes	0.30 Percentage of reticulocytes/erythrocytes Standard Deviation 0.141	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular haemoglobin concentration and haemoglobin is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin Concentration and Haemoglobin Erythrocyte mean corpuscular haemoglobin concentration	-10.0 g/L	0.0 g/L Standard Deviation 0.0	—
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin Concentration and Haemoglobin Haemoglobin	-6.0 g/L	9.0 g/L Standard Deviation 4.24	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular haemoglobin is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Haemoglobin	-1.0 picograms (pg)	0.5 picograms (pg) Standard Deviation 0.71	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in erythrocyte mean corpuscular volume is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Erythrocyte Mean Corpuscular Volume	2.0 femtoliter (fL)	2.5 femtoliter (fL) Standard Deviation 0.71	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Erythrocytes	-0.10 10^12 cells/liter	0.20 10^12 cells/liter Standard Deviation 0.141	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Specific Gravity	-0.0050 Ratio	0.0025 Ratio Standard Deviation 0.01061	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	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.	Cohort 1: Belcesiran n=1 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Urine Erythrocytes and Urine Leucocytes Urine leucocytes	—	0.0 per high power field (/HPF)	—
Change From Baseline in Clinical Laboratory Tests: Urine Erythrocytes and Urine Leucocytes Urine erythrocytes	—	3.0 per high power field (/HPF)	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Potential of Hydrogen (pH)	0.00 pH	-0.75 pH Standard Deviation 1.061	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Change from baseline (Day 1) to week 96 in activated partial thromboplastin time and prothrombin time is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Activated Partial Thromboplastin Time and Prothrombin Time Activated partial thromboplastin time	0.40 seconds (sec)	1.55 seconds (sec) Standard Deviation 2.333	—
Change From Baseline in Clinical Laboratory Tests: Activated Partial Thromboplastin Time and Prothrombin Time Prothrombin time	-0.50 seconds (sec)	0.40 seconds (sec) Standard Deviation 0.990	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

Population: 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.

Change from baseline (Day 1) to week 96 in prothrombin international normalized ratio is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Prothrombin International Normalized Ratio	0.00 Ratio	0.00 Ratio Standard Deviation 0.141	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
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 Alpha fetoprotein	0.30 nanograms per milliter (ng/mL)	2.90 nanograms per milliter (ng/mL) Standard Deviation 2.687	—
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 Biomarker hyaluronic acid	—	137.305 nanograms per milliter (ng/mL) Standard Deviation 310.3704	—
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 Biomarker matrix metalloproteinase 9	—	-193.65 nanograms per milliter (ng/mL) Standard Deviation 239.356	—
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 Biomarker procollagen 3 N-terminal propeptide	—	-0.655 nanograms per milliter (ng/mL) Standard Deviation 0.5020	—
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 Biomarker tissue inhibitor of metalloproteinase 1	—	-83.25 nanograms per milliter (ng/mL) Standard Deviation 8.980	—
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 Complement C3a	139.70 nanograms per milliter (ng/mL)	-5.60 nanograms per milliter (ng/mL) Standard Deviation 5.657	—
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 Complement C5a	1.890 nanograms per milliter (ng/mL)	-1.785 nanograms per milliter (ng/mL) Standard Deviation 0.6152	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: C-Reactive Protein	4.30 mg/L	-0.30 mg/L Standard Deviation 0.849	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Complement Bb	0.240 microgram per milliliter (ug/mL)	0.325 microgram per milliliter (ug/mL) Standard Deviation 0.2616	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 96

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

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	Cohort 1: Belcesiran n=2 Participants 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.	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.
Change From Baseline in Clinical Laboratory Tests: Complement Total (CH50)	6.530 equivalent unit per milliliter (U Eq/mL)	-46.900 equivalent unit per milliliter (U Eq/mL) Standard Deviation 40.1071	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 24

Population: 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.

Change from baseline (Day 1) to week 24 in serum AAT protein concentrations in Cohort 1 is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=4 Participants 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.	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.	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.
Cohort 1: Change From Baseline in Serum Alpha-1 Antitrypsin (AAT) Protein Concentrations	-0.30 g/L Standard Deviation 0.120	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1), week 48

Population: 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.

Change from baseline (Day 1) to week 48 in serum AAT protein concentrations in Cohort 2 is presented.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=3 Participants 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.	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.	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.
Cohort 2: Change From Baseline in Serum AAT Protein Concentrations	-0.50 g/L Standard Deviation 0.094	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1), week 48

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Pooled Placebo n=1 Participants 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.	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.	Cohort 2: Belcesiran n=3 Participants 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.
Change From Baseline in Liver Fibrosis Ishak Score	1.0 unit on a score	—	-1.0 unit on a score Standard Deviation 0.00

Adverse Events

Pooled Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 1: Belcesiran

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 2: Belcesiran

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pooled Placebo n=5 participants at risk 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.	Cohort 1: Belcesiran n=5 participants at risk 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.	Cohort 2: Belcesiran n=6 participants at risk 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.
Cardiac disorders Acute myocardial infarction	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	16.7% 1/6 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Cardiac disorders Atrial fibrillation	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	20.0% 1/5 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/6 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Infections and infestations Erysipelas	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	16.7% 1/6 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Infections and infestations Pneumonia	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	20.0% 1/5 • Number of events 3 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/6 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Infections and infestations Viral infection	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	16.7% 1/6 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	16.7% 1/6 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Investigations Pulmonary function test decreased	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	16.7% 1/6 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	20.0% 1/5 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/6 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Nervous system disorders Hepatic encephalopathy	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	20.0% 1/5 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/6 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.
Psychiatric disorders Depression	0.00% 0/5 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	20.0% 1/5 • Number of events 1 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.	0.00% 0/6 • Up to 2.6 years Results are based on safety population. Safety Population was defined as all participants randomly assigned to study intervention and who received at least 1 dose of study drug. Presented AEs are TEAEs. AEs were defined as TEAEs if they had start date on or after administration of study drug during treatment period, or if they occurred prior to administration of study drug and worsened in severity/grade or relationship to study drug after administration during treatment period.

Other adverse events

Additional Information

Clinical Reporting Office (2834)

Dicerna Pharmaceuticals, Inc., a Novo Nordisk company

Phone: (+1) 866-867-7178

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Publication restrictions are in place

Restriction type: OTHER