Trial Outcomes & Findings for Factor XI LICA to Reduce Events Such as Heart Attack and Stroke in Patients Whose Kidneys Are no Longer Able to Work as They Should and Require Treatment to Filter Wastes From the Blood: Focus is on the Safety of BAY2976217 and the Way the Body Absorbs, Distributes and Removes the Study Drug (NCT NCT04534114)

NCT ID: NCT04534114

Last Updated: 2023-07-03

Results Overview

MB is defined as symptomatic bleeding and: 1) Fatal bleeding, and/or; 2) Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or; 3) Bleeding causing a fall in hemoglobin level of 20 g/L (2.0 g/dL) (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. CRNMB is defined as any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: 1) Requiring medical intervention by a healthcare professional; 2) Leading to hospitalization or increased level of care; 3) Prompting a face-to-face evaluation. n/100 person-years: number of subjects with incident events divided by the cumulative at-risk time in the reference population, where a subject is no longer at risk once an incident event occurred.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 307 participants
• Primary outcome timeframe: Up to 24 weeks
• Results posted on: 2023-07-03

Participant Flow

Study was conducted at 69 study centers in 15 countries between 04-SEP-2020 (first participant first visit) and 12-MAY-2022 (last participant last visit).

From 359 participants screened, 51 participants were screening failure and a total of 308 participants were randomized and 307 were treated either with fesomersen or placebo.

Participant milestones

Measure	Fesomersen 40 mg Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Main Treatment Period STARTED	77	79	76	75
Main Treatment Period COMPLETED	67	66	64	61
Main Treatment Period NOT COMPLETED	10	13	12	14
Extension Treatment Period STARTED	62	61	63	58
Extension Treatment Period COMPLETED	59	57	62	53
Extension Treatment Period NOT COMPLETED	3	4	1	5

Reasons for withdrawal

Measure	Fesomersen 40 mg Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Main Treatment Period COVID-19 pandemic: Participant decision	0	1	0	0
Main Treatment Period COVID-19 pandemic: Death	0	1	0	2
Main Treatment Period COVID-19 pandemic: Adverse event	0	1	1	0
Main Treatment Period COVID-19 pandemic: withdrawal following protocol	1	3	3	1
Main Treatment Period Physician Decision	0	0	0	1
Main Treatment Period Death	1	0	0	1
Main Treatment Period Other reason	1	1	0	0
Main Treatment Period Participant decision	1	3	3	1
Main Treatment Period Protocol-specified withdrawal criterion met	2	1	4	6
Main Treatment Period Adverse Event	4	2	1	2
Extension Treatment Period COVID-19 pandemic: Death	0	0	0	1
Extension Treatment Period COVID-19 pandemic: withdrawal following protocol	1	0	0	0
Extension Treatment Period Other reason	0	1	0	0
Extension Treatment Period Death	0	0	1	2
Extension Treatment Period Adverse Event	0	1	0	1
Extension Treatment Period Protocol-specified Withdrawal Criterion Met	2	2	0	1

Baseline Characteristics

Factor XI LICA to Reduce Events Such as Heart Attack and Stroke in Patients Whose Kidneys Are no Longer Able to Work as They Should and Require Treatment to Filter Wastes From the Blood: Focus is on the Safety of BAY2976217 and the Way the Body Absorbs, Distributes and Removes the Study Drug

Baseline characteristics by cohort

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 Participants Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Total n=307 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	74 Participants n=5 Participants	73 Participants n=7 Participants	75 Participants n=5 Participants	72 Participants n=4 Participants	294 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Age, Continuous	60.4 Years STANDARD_DEVIATION 13.2 • n=5 Participants	58.0 Years STANDARD_DEVIATION 14.4 • n=7 Participants	57.7 Years STANDARD_DEVIATION 13.3 • n=5 Participants	58.6 Years STANDARD_DEVIATION 11.9 • n=4 Participants	58.7 Years STANDARD_DEVIATION 13.2 • n=21 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	20 Participants n=7 Participants	30 Participants n=5 Participants	22 Participants n=4 Participants	107 Participants n=21 Participants
Sex: Female, Male Male	42 Participants n=5 Participants	59 Participants n=7 Participants	46 Participants n=5 Participants	53 Participants n=4 Participants	200 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants	13 Participants n=4 Participants	44 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	8 Participants n=21 Participants
Race (NIH/OMB) White	62 Participants n=5 Participants	70 Participants n=7 Participants	61 Participants n=5 Participants	61 Participants n=4 Participants	254 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.

MB is defined as symptomatic bleeding and: 1) Fatal bleeding, and/or; 2) Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or; 3) Bleeding causing a fall in hemoglobin level of 20 g/L (2.0 g/dL) (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. CRNMB is defined as any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: 1) Requiring medical intervention by a healthcare professional; 2) Leading to hospitalization or increased level of care; 3) Prompting a face-to-face evaluation. n/100 person-years: number of subjects with incident events divided by the cumulative at-risk time in the reference population, where a subject is no longer at risk once an incident event occurred.

Outcome measures

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 Participants Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Incidence of Composite of Major Bleeding (MB) and Clinically-relevant Non-major Bleeding (CRNMB) During the Main Treatment Period and Within the On-treatment Time Window, as Assessed by Blinded Central Independent Adjudication Committee (CIAC)	9.0 n/100 person-years Interval 2.5 to 18.9	9.1 n/100 person-years Interval 2.5 to 19.1	6.1 n/100 person-years Interval 1.1 to 14.5	9.7 n/100 person-years Interval 2.7 to 20.4

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.

MB is defined as symptomatic bleeding and: 1) Fatal bleeding, and/or; 2) Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or; 3) Bleeding causing a fall in hemoglobin level of 20 g/L (2.0 g/dL) (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. CRNMB is defined as any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: 1) Requiring medical intervention by a healthcare professional; 2) Leading to hospitalization or increased level of care; 3) Prompting a face-to-face evaluation. n/100 person-years: number of subjects with incident events divided by the cumulative at-risk time in the reference population, where a subject is no longer at risk once an incident event occurred.

Outcome measures

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 Participants Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Incidence of Composite of MB and CRNMB During the Main and Extended Treatment Periods and Within the On-treatment Time Window, as Assessed by Blinded CIAC	10.7 n/100 person-years Interval 4.2 to 19.7	8.6 n/100 person-years Interval 2.9 to 16.7	6.4 n/100 person-years Interval 1.7 to 13.3	7.0 n/100 person-years Interval 1.9 to 14.8

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.

TEAEs were analyzed during the on-treatment time window within the main treatment period in the safety analysis set (SAF). Data observed from the randomization date until the end of the main treatment period. TEAEs were defined as events occurring after first study intervention administration and up to 20 weeks after last study intervention administration.

Outcome measures

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 Participants Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity Any TEAE	54 Participants	56 Participants	55 Participants	55 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity Maximum intensity for any TEAE: Mild	28 Participants	28 Participants	22 Participants	27 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity Maximum intensity for any TEAE: Moderate	17 Participants	24 Participants	28 Participants	19 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity Maximum intensity for any TEAE: Severe	9 Participants	4 Participants	5 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.

TEAEs were analyzed during during main and extended treatment periods in the safety analysis set (SAF). Data observed from the randomization date until the end of the extension treatment period. TEAEs were defined as events occurring after first study intervention administration and up to 20 weeks after last study intervention administration.

Outcome measures

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 Participants Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity Any TEAE	61 Participants	62 Participants	58 Participants	56 Participants
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity Maximum intensity for any TEAE: Mild	26 Participants	25 Participants	20 Participants	26 Participants
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity Maximum intensity for any TEAE: Moderate	24 Participants	31 Participants	30 Participants	18 Participants
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity Maximum intensity for any TEAE: Severe	11 Participants	6 Participants	8 Participants	12 Participants

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: Safety analysis set (SAF) includes all randomized participants who received at least one dose of the study intervention according to actual treatment arm received.

TEAEs occurring from first study intervention intake until 20 weeks after last study intervention intake.

Outcome measures

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 Participants Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Until 20 Weeks After the Last Study Intervention Dose and Their Severity Any TEAE	64 Participants	63 Participants	62 Participants	59 Participants
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Until 20 Weeks After the Last Study Intervention Dose and Their Severity Maximum intensity for any TEAE: Mild	21 Participants	21 Participants	18 Participants	21 Participants
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Until 20 Weeks After the Last Study Intervention Dose and Their Severity Maximum intensity for any TEAE: Moderate	28 Participants	33 Participants	33 Participants	22 Participants
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Until 20 Weeks After the Last Study Intervention Dose and Their Severity Maximum intensity for any TEAE: Severe	15 Participants	9 Participants	11 Participants	16 Participants

SECONDARY outcome

Timeframe: At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141)

Population: Pharmacokinetic analysis set (PKS) includes all fesomersen-treated participants with at least 1 PK sample in accordance with the PK sampling schedule and without deviation from the protocol that would interfere with the evaluation of the PK data were included in the PK analysis. Only those participants who have sample collection with data available at the specified time points were analyzed.

Trough (pre-dose) fesomersen-equivalent plasma concentrations (Ctrough) for 3 dose levels of fesomersen were summarized descriptively by dose level and visit: Visit 12, Visit 14, Visit 16, Visit 18 (main treatment period). Ctrough was not measured for the placebo group.

Outcome measures

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen Visit 12	0.000454 μg/mL Geometric Coefficient of Variation 118.753791	0.000704 μg/mL Geometric Coefficient of Variation 80.938271	0.001186 μg/mL Geometric Coefficient of Variation 76.691406	—
Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen Visit 14	0.000490 μg/mL Geometric Coefficient of Variation 92.511801	0.000792 μg/mL Geometric Coefficient of Variation 82.170296	0.001246 μg/mL Geometric Coefficient of Variation 97.530820	—
Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen Visit 16	0.000572 μg/mL Geometric Coefficient of Variation 85.974878	0.000789 μg/mL Geometric Coefficient of Variation 68.188121	0.001346 μg/mL Geometric Coefficient of Variation 81.805680	—
Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen Visit 18	0.000521 μg/mL Geometric Coefficient of Variation 106.848825	0.000828 μg/mL Geometric Coefficient of Variation 91.024162	0.001424 μg/mL Geometric Coefficient of Variation 92.709743	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Pharmacodynamic set (PDS) includes all participants with at least 1 PD sample in accordance with the PD sampling schedule and without deviation from the protocol that would interfere with the evaluation of the PD data were included in the PD analysis. Data were not collected for this outcome measure.

The secondary endpoint of change in FXI antigen levels during the main treatment period was an optional secondary endpoint only as mentioned in the integrated clinical protocol amendment version 3.0 and was not analyzed in this study as the FXI activity assay is sufficient to describe the effect on FXI level in plasma.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Days 1 (Pre-Dose and 5 hours post-dose), 2, 8, 15, 22, 29 (Pre-dose and 5 hours post-dose), 43, 57 (Pre-dose), 71, 85 (Pre-dose), 113 (Pre-dose), 141 (Pre-dose),148, 155, 162, and 169 (Pre-dose)

Population: Pharmacodynamic set (PDS) includes all participants with at least 1 PD sample in accordance with the PD sampling schedule and without deviation from the protocol that would interfere with the evaluation of the PD data were included in the PD analysis.

The FXIa activity was measured by a fluorogenic activated FXIa activity (AXIA) assay. Absolute change from baseline at each visit until Visit 22 (Day 169) are reported.

Outcome measures

Measure	Fesomersen 40 mg n=77 Participants Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 Participants Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 Participants Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 Participants Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 11 (Day 43)	0.47 U/mL Standard Deviation 0.29	0.59 U/mL Standard Deviation 0.25	0.76 U/mL Standard Deviation 0.27	0.09 U/mL Standard Deviation 0.08
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 14 (Day 85): Pre-dose	0.46 U/mL Standard Deviation 0.27	0.59 U/mL Standard Deviation 0.26	0.72 U/mL Standard Deviation 0.24	0.14 U/mL Standard Deviation 0.12
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 22 (Day 169): Pre-dose	0.46 U/mL Standard Deviation 0.29	0.59 U/mL Standard Deviation 0.28	0.73 U/mL Standard Deviation 0.25	0.17 U/mL Standard Deviation 0.21
Maximum Change in FXI Activity Levels During the Main Treatment Period Baseline	0.00 U/mL Standard Deviation 0.00	0.00 U/mL Standard Deviation 0.00	0.00 U/mL Standard Deviation 0.00	0.00 U/mL Standard Deviation 0.00
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 5 (Day 1): Pre-dose	0.06 U/mL Standard Deviation 0.06	0.05 U/mL Standard Deviation 0.06	0.05 U/mL Standard Deviation 0.05	0.04 U/mL Standard Deviation 0.05
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 5 (Day 1): 5 Hours	0.09 U/mL Standard Deviation 0.09	0.11 U/mL Standard Deviation 0.12	0.13 U/mL Standard Deviation 0.13	0.10 U/mL Standard Deviation 0.08
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 6 (Day 2): 22 Hours	0.13 U/mL Standard Deviation 0.11	0.12 U/mL Standard Deviation 0.12	0.15 U/mL Standard Deviation 0.13	0.14 U/mL Standard Deviation 0.13
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 7 (Day 8)	0.21 U/mL Standard Deviation 0.15	0.32 U/mL Standard Deviation 0.15	0.43 U/mL Standard Deviation 0.18	0.08 U/mL Standard Deviation 0.07
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 8 (Day 15)	0.34 U/mL Standard Deviation 0.23	0.48 U/mL Standard Deviation 0.21	0.61 U/mL Standard Deviation 0.24	0.12 U/mL Standard Deviation 0.09
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 9 (Day 22)	0.37 U/mL Standard Deviation 0.26	0.50 U/mL Standard Deviation 0.23	0.63 U/mL Standard Deviation 0.25	0.11 U/mL Standard Deviation 0.09
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 10 (Day 29): Pre-dose	0.34 U/mL Standard Deviation 0.26	0.44 U/mL Standard Deviation 0.21	0.60 U/mL Standard Deviation 0.25	0.09 U/mL Standard Deviation 0.07
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 10 (Day 29): 5 Hours	0.32 U/mL Standard Deviation 0.25	0.43 U/mL Standard Deviation 0.22	0.58 U/mL Standard Deviation 0.25	0.12 U/mL Standard Deviation 0.14
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 12 (Day 57): Pre-dose	0.42 U/mL Standard Deviation 0.26	0.55 U/mL Standard Deviation 0.24	0.69 U/mL Standard Deviation 0.28	0.11 U/mL Standard Deviation 0.10
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 13 (Day 71)	0.52 U/mL Standard Deviation 0.26	0.66 U/mL Standard Deviation 0.24	0.76 U/mL Standard Deviation 0.25	0.15 U/mL Standard Deviation 0.13
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 16 (Day 113): Pre-dose	0.46 U/mL Standard Deviation 0.26	0.57 U/mL Standard Deviation 0.28	0.75 U/mL Standard Deviation 0.25	0.16 U/mL Standard Deviation 0.16
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 18 (Day 141): Pre-dose	0.47 U/mL Standard Deviation 0.27	0.56 U/mL Standard Deviation 0.28	0.72 U/mL Standard Deviation 0.25	0.12 U/mL Standard Deviation 0.09
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 19 (Day 148)	0.52 U/mL Standard Deviation 0.27	0.63 U/mL Standard Deviation 0.29	0.76 U/mL Standard Deviation 0.26	0.15 U/mL Standard Deviation 0.16
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 20 (Day 155)	0.52 U/mL Standard Deviation 0.28	0.65 U/mL Standard Deviation 0.29	0.77 U/mL Standard Deviation 0.25	0.15 U/mL Standard Deviation 0.17
Maximum Change in FXI Activity Levels During the Main Treatment Period Visit 21 (Day 162)	0.50 U/mL Standard Deviation 0.30	0.64 U/mL Standard Deviation 0.28	0.75 U/mL Standard Deviation 0.26	0.16 U/mL Standard Deviation 0.20

Adverse Events

Fesomersen 40 mg

Serious events: 19 serious events

Other events: 31 other events

Deaths: 2 deaths

Fesomersen 80 mg

Serious events: 18 serious events

Other events: 27 other events

Deaths: 1 deaths

Fesomersen 120 mg

Serious events: 17 serious events

Other events: 30 other events

Deaths: 2 deaths

Placebo

Serious events: 20 serious events

Other events: 21 other events

Deaths: 7 deaths

Serious adverse events

Measure	Fesomersen 40 mg n=77 participants at risk Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 participants at risk Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 participants at risk Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 participants at risk Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Investigations Klebsiella test positive	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Metabolism and nutrition disorders Hyperkalaemia	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Vascular disorders Superficial vein thrombosis	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Blood and lymphatic system disorders Spleen ischaemia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Arrhythmia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Atrial fibrillation	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Atrial flutter	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Cardiac arrest	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Cardiac failure congestive	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Coronary artery disease	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Supraventricular tachycardia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Ventricular fibrillation	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Bradyarrhythmia	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Cardiac disorders Acute coronary syndrome	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Abdominal adhesions	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Gastritis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Intestinal obstruction	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Large intestine perforation	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Small intestinal haemorrhage	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
General disorders Chest pain	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
General disorders Pyrexia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
General disorders Swelling	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
General disorders Device related thrombosis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Hepatobiliary disorders Bile duct stone	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Hepatobiliary disorders Cholangitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Hepatobiliary disorders Cholecystitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Hepatobiliary disorders Cholecystitis acute	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Hepatobiliary disorders Hepatic ischaemia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Cellulitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.7% 2/75 • Number of events 2 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Diverticulitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Gangrene	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Orchitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Osteomyelitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Peritonitis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Pneumonia	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Sepsis	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Staphylococcal bacteraemia	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Coronavirus infection	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Sepsis syndrome	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Staphylococcal sepsis	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations Vascular access site infection	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations COVID-19	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.3% 4/76 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.7% 2/75 • Number of events 2 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Infections and infestations COVID-19 pneumonia	2.6% 2/77 • Number of events 2 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.1% 4/79 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.6% 2/76 • Number of events 2 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	4.0% 3/75 • Number of events 7 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Concussion	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Shunt occlusion	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Arteriovenous graft thrombosis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Arteriovenous graft site haemorrhage	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Shunt stenosis	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Vascular graft thrombosis	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Delayed graft function	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Injury, poisoning and procedural complications Arteriovenous graft site pseudoaneurysm	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Investigations Alanine aminotransferase increased	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Investigations Transplant evaluation	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neoplasm	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Nervous system disorders Carotid artery stenosis	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Nervous system disorders Cerebral ischaemia	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Nervous system disorders Encephalopathy	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Nervous system disorders Loss of consciousness	1.3% 1/77 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Nervous system disorders Transient ischaemic attack	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Nervous system disorders Post cardiac arrest syndrome	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Surgical and medical procedures Renal transplant	3.9% 3/77 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.1% 4/79 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Vascular disorders Hypertension	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Vascular disorders Subclavian vein thrombosis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/79 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Vascular disorders Peripheral artery thrombosis	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/79 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.

Other adverse events

Measure	Fesomersen 40 mg n=77 participants at risk Participants received monthly subcutaneous treatment with 40 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 80 mg n=79 participants at risk Participants received monthly subcutaneous treatment with 80 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Fesomersen 120 mg n=76 participants at risk Participants received monthly subcutaneous treatment with 120 mg fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.	Placebo n=75 participants at risk Participants received monthly subcutaneous treatment with matching placebo to fesomersen (Factor XI LICA). LICA=Ligand conjugated antisense oligonucleotide.
Blood and lymphatic system disorders Anaemia	5.2% 4/77 • Number of events 6 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.1% 4/79 • Number of events 9 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.9% 3/76 • Number of events 5 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.3% 4/75 • Number of events 5 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Blood and lymphatic system disorders Thrombocytopenia	3.9% 3/77 • Number of events 5 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	8.9% 7/79 • Number of events 13 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	9.2% 7/76 • Number of events 11 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.7% 2/75 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Diarrhoea	6.5% 5/77 • Number of events 9 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.5% 2/79 • Number of events 2 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.9% 3/76 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.7% 2/75 • Number of events 2 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Gastrointestinal disorders Nausea	3.9% 3/77 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.1% 4/79 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/76 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	4.0% 3/75 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
General disorders Pyrexia	9.1% 7/77 • Number of events 8 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.8% 3/79 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.6% 2/76 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.3% 4/75 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Investigations N-terminal prohormone brain natriuretic peptide increased	0.00% 0/77 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.1% 4/79 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/76 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	0.00% 0/75 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Musculoskeletal and connective tissue disorders Back pain	5.2% 4/77 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.8% 3/79 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.3% 4/76 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.7% 2/75 • Number of events 5 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Musculoskeletal and connective tissue disorders Muscle spasms	5.2% 4/77 • Number of events 10 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.8% 3/79 • Number of events 5 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	6.6% 5/76 • Number of events 7 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	4.0% 3/75 • Number of events 13 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Nervous system disorders Headache	5.2% 4/77 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.8% 3/79 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.9% 3/76 • Number of events 5 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Psychiatric disorders Insomnia	2.6% 2/77 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.1% 4/79 • Number of events 4 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	3.9% 3/76 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	2.7% 2/75 • Number of events 3 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Vascular disorders Hypertension	3.9% 3/77 • Number of events 5 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	6.3% 5/79 • Number of events 9 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	7.9% 6/76 • Number of events 8 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	9.3% 7/75 • Number of events 8 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.
Vascular disorders Hypotension	7.8% 6/77 • Number of events 27 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	5.1% 4/79 • Number of events 12 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	10.5% 8/76 • Number of events 12 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.	1.3% 1/75 • Number of events 1 • From first study intervention up to 64 Weeks. Adverse event reporting for the all-cause mortality considers all deaths that occurred at any time during the study before the last contact, up to 64 Weeks.

Additional Information

Therapeutic Area Head

Bayer AG

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

• Principal investigator is a sponsor employee The results of this study may be published or presented at scientific meetings. If this is foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission. This allows the sponsor to protect proprietary information and to provide comments.
• Publication restrictions are in place

Restriction type: OTHER