Trial Outcomes & Findings for A Phase 2b Study of Icosabutate in Fatty Liver Disease (NCT NCT04052516)

NCT ID: NCT04052516

Last Updated: 2025-02-28

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

280 participants

Primary outcome timeframe

52 weeks

Results posted on

2025-02-28

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Overall Study STARTED	92	93	95
Overall Study Safety Population	91	92	95
Overall Study ITT	91	92	95
Overall Study mITT	75	76	77
Overall Study 3-Panel mITT	75	76	77
Overall Study COMPLETED	79	78	78
Overall Study NOT COMPLETED	13	15	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Overall Study Withdrawal by Subject	4	5	6
Overall Study Adverse Event	3	2	8
Overall Study Lost to Follow-up	2	5	3
Overall Study Protocol Violation	1	1	0
Overall Study Death	1	0	0
Overall Study Physician Decision	0	1	0
Overall Study Pregnancy	1	0	0
Overall Study Requirement of prohibited concomitant medication	1	0	0
Overall Study Reason not recorded	0	1	0

Baseline Characteristics

A Phase 2b Study of Icosabutate in Fatty Liver Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=75 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=76 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=77 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Total n=228 Participants Total of all reporting groups
Age, Continuous	54.0 years STANDARD_DEVIATION 11.15 • n=5 Participants	53.3 years STANDARD_DEVIATION 10.52 • n=7 Participants	51.8 years STANDARD_DEVIATION 10.26 • n=5 Participants	53.0 years STANDARD_DEVIATION 10.64 • n=4 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	55 Participants n=7 Participants	51 Participants n=5 Participants	158 Participants n=4 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	21 Participants n=7 Participants	26 Participants n=5 Participants	70 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants	31 Participants n=7 Participants	29 Participants n=5 Participants	92 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=5 Participants	44 Participants n=7 Participants	45 Participants n=5 Participants	131 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) White	72 Participants n=5 Participants	72 Participants n=7 Participants	71 Participants n=5 Participants	215 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Body mass index	35.94 kg/m^2 STANDARD_DEVIATION 6.230 • n=5 Participants	36.73 kg/m^2 STANDARD_DEVIATION 5.732 • n=7 Participants	37.32 kg/m^2 STANDARD_DEVIATION 6.047 • n=5 Participants	36.67 kg/m^2 STANDARD_DEVIATION 6.006 • n=4 Participants
Alcohol use Current	44 Participants n=5 Participants	40 Participants n=7 Participants	40 Participants n=5 Participants	124 Participants n=4 Participants
Alcohol use Former	10 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants	30 Participants n=4 Participants
Alcohol use Never	20 Participants n=5 Participants	28 Participants n=7 Participants	25 Participants n=5 Participants	73 Participants n=4 Participants
Alcohol use Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Type 2 Diabetes status Diabetic	35 Participants n=5 Participants	40 Participants n=7 Participants	39 Participants n=5 Participants	114 Participants n=4 Participants
Type 2 Diabetes status Non-diabetic	40 Participants n=5 Participants	36 Participants n=7 Participants	38 Participants n=5 Participants	114 Participants n=4 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: 3-Panel Modified Intent-To-Treat (mITT) Population - The 3-Panel mITT Population included all patients who had a baseline and Week 52 (or ET, if applicable) liver biopsy read and fulfilled eligibility criteria based on the 3-panel read paradigm. This population was considered the primary population for the efficacy analysis of the histology data. Biopsy fibrosis score F2/F3

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=52 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=53 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Percentage of Patients With Resolution of NASH, Defined as Disappearance of Ballooning (Score = 0) With Lobular Inflammation Score 0 or 1, With no Worsening of Fibrosis.	8.7 percentage of participants	17.3 percentage of participants	20.8 percentage of participants

SECONDARY outcome

Timeframe: 52 weeks

Population: 3-Panel mITT population. Biopsy fibrosis score F2/F3

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=52 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=53 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Percentage of Patients With Fibrosis Improvement, Defined as Greater Than or Equal to 1 Stage of Fibrosis Improvement and no Worsening of Steatohepatitis (Inflammation/Ballooning).	13.0 percentage of participants	26.9 percentage of participants	24.5 percentage of participants

SECONDARY outcome

Timeframe: 52 weeks

Population: 3-Panel mITT population. Biopsy fibrosis score F2/F3.

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=52 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=53 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Percentage of Patients With Fibrosis Improvement, Defined as Greater Than or Equal to 1 Stage of Fibrosis Improvement.	13.0 percentage of participants	30.8 percentage of participants	28.3 percentage of participants

SECONDARY outcome

Timeframe: 52 weeks

Population: Results are presented for those participants in the 3-panel mITT population who had results for these parameters at Week 52.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=56 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=66 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Changes in the Liver Enzymes Aspartate Aminotransferase (AST)U/L, Alanine Aminotransferase ( ALT)U/L and Gamma Glutamyl Transferase (GGT) U/L From Baseline Aspartate Aminotransferase	-8.2 U/L Standard Error 3.18	-14.9 U/L Standard Error 3.46	-18.5 U/L Standard Error 3.13
Changes in the Liver Enzymes Aspartate Aminotransferase (AST)U/L, Alanine Aminotransferase ( ALT)U/L and Gamma Glutamyl Transferase (GGT) U/L From Baseline Alanine Aminotransferase	-9.8 U/L Standard Error 3.73	-27.9 U/L Standard Error 4.05	-30.1 U/L Standard Error 3.65
Changes in the Liver Enzymes Aspartate Aminotransferase (AST)U/L, Alanine Aminotransferase ( ALT)U/L and Gamma Glutamyl Transferase (GGT) U/L From Baseline Gamma Glutamyl Transferase	-5.1 U/L Standard Error 5.41	-27.9 U/L Standard Error 5.75	-32.7 U/L Standard Error 5.26

SECONDARY outcome

Timeframe: 52 weeks

Population: Results are presented for those participants in the 3-panel mITT population who had results for this parameter at Week 52

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=56 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=66 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change in Bilirubin Micromol/L From Baseline	0.56 micromol/L Standard Error 0.332	-1.11 micromol/L Standard Error 0.362	-1.49 micromol/L Standard Error 0.325

SECONDARY outcome

Timeframe: 52 weeks

Population: 3-panel mITT population

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=58 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=67 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change From Baseline in Inflammation Marker hsCRP	1.089 mg/L Standard Error 0.8095	-1.297 mg/L Standard Error 0.8953	-3.382 mg/L Standard Error 0.7978

SECONDARY outcome

Timeframe: 52 weeks

Population: Results are presented for those participants in the 3-panel mITT population who had results for this parameter at Week 52

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=54 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=64 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change From Baseline in Fibrosis Activity Marker Pro-C3	-4.33 micrograms/L Standard Error 2.830	-3.68 micrograms/L Standard Error 3.023	-11.76 micrograms/L Standard Error 2.762

SECONDARY outcome

Timeframe: 52 weeks

Population: Results are presented for those participants in the 3-panel mITT population who had results for these parameters at Week 52.

ELF is a blood test that measures liver fibrosis by analyzing three markers in the blood: Hyaluronic acid (HA), Procollagen III amino-terminal peptide (PIIINP), and Tissue inhibitor of matrix metalloproteinase 1 (TIMP-1). The higher the score the higher the levels of markers in the blood. ELF score = 2.278 + 0.851 × ln(HA) + 0.751 × ln(PIIINP) + 0.394 × ln(TIMP-1). As the score is a composite measure of the levels of three markers in the blood, there is not a finite range for this parameter.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=54 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=64 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change From Baseline in Fibrosis Activity Marker Enhanced Liver Fibrosis (ELF) Test	-0.051 score Standard Error 0.0993	-0.125 score Standard Error 0.1087	-0.370 score Standard Error 0.0983

SECONDARY outcome

Timeframe: 52 weeks

Population: 3-panel mITT population

HOMA-IR is a measure of insulin resistance and metabolic status. The higher the score, the higher the level of insulin resistance. HOMA-IR = fasting glucose \[mmol/L)\] × fasting insulin \[mIU/L\]/22.5. As HOMA-IR is a composite score using 2 parameters, it does not have a finite range.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=58 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=67 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)	0.609 score Standard Error 1.3453	-2.810 score Standard Error 1.4733	-3.794 score Standard Error 1.3203

SECONDARY outcome

Timeframe: 52 weeks

Population: Results are presented for those participants in the 3-panel mITT population who had results for these parameters at Week 52.

The disease activity score can range from 0 to 8 and is calculated by the sum of scores of steatosis (0-3), lobular inflammation (0-3) and hepatocyte ballooning (0-2). The higher the score the more severe the disease.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=58 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=66 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change From Baseline in Composite Disease Activity Score (Composite NASH Score of Inflammation, Ballooning, Fibrosis)	-0.2 score on a scale Standard Deviation 1.68	-0.7 score on a scale Standard Deviation 1.84	-0.9 score on a scale Standard Deviation 1.56

SECONDARY outcome

Timeframe: 52 weeks

Population: Results are presented for those participants in the 3-panel mITT population who had results for these parameters at Week 52.

A histological scoring system that assesses a liver biopsy and gives scores for steatosis (0-3), lobular inflammation (0-3), and hepatocyte ballooning (0-2) giving a total score of (0-8). The higher the score the more severe the disease

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=58 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=65 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change From Baseline in Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)	-0.9 score on a scale Standard Deviation 1.36	-0.9 score on a scale Standard Deviation 1.51	-1.3 score on a scale Standard Deviation 1.65

SECONDARY outcome

Timeframe: 52 weeks

Population: 3-panel mITT population

Changes in scores for the individual component parts of the Nonalcoholic fatty liver disease (NAFLD) activity score (NAS) as judged by a pathologist examining sections from a liver biopsy; steatosis (range 0-3), lobular inflammation (range 0-3), and hepatocyte ballooning (range 0-2) In all cases a higher number denotes more severe disease activity

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=58 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=67 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Changes in Individual Histological Scores for Steatosis, Ballooning, Inflammation, and Fibrosis From Baseline Steatosis grade	-0.4 score on a scale Standard Deviation 0.62	-0.2 score on a scale Standard Deviation 0.65	-0.4 score on a scale Standard Deviation 0.81
Changes in Individual Histological Scores for Steatosis, Ballooning, Inflammation, and Fibrosis From Baseline Lobular inflammation score	-0.2 score on a scale Standard Deviation 0.62	-0.4 score on a scale Standard Deviation 0.67	-0.5 score on a scale Standard Deviation 0.61
Changes in Individual Histological Scores for Steatosis, Ballooning, Inflammation, and Fibrosis From Baseline Hepatocyte ballooning score	-0.3 score on a scale Standard Deviation 0.79	-0.3 score on a scale Standard Deviation 0.84	-0.4 score on a scale Standard Deviation 0.78

SECONDARY outcome

Timeframe: 52 weeks

Population: Results are presented for those participants in the 3-panel mITT population who had results for these parameters at Week 52.

MRI-PDFF is a quantitative imaging biomarker that measures the fat fraction of tissue by correcting factors influencing magnetic resonance signal intensity.

Outcome measures

Outcome measures
Measure	Placebo n=62 Participants Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=58 Participants Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=65 Participants Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Change From Baseline in Magnetic Resonance Imaging-Proton Density-Fat Fraction (MRI-PDFF)	-4.37 Percentage of fat Standard Deviation 7.185	-1.33 Percentage of fat Standard Deviation 5.356	-0.95 Percentage of fat Standard Deviation 8.206

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 82 other events

Deaths: 1 deaths

Icosabutate 300mg

Serious events: 5 serious events

Other events: 80 other events

Deaths: 0 deaths

Icosabutate 600mg

Serious events: 8 serious events

Other events: 80 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Scientific Officer

NorthSea Therapeutics BV

Phone: 31 035760 65 05

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Each Investigator is obligated to keep data pertaining to the study confidential. The Investigator must consult with the Sponsor before any study data are submitted for publication. The Sponsor reserves the right to deny publication rights until mutual agreement on the content, format, interpretation of data in the manuscript, and journal selected for publication are achieved.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=91 participants at risk Placebo oral capsules taken one daily for 52 weeks Placebo: Matching placebo oral capsule	Icosabutate 300mg n=92 participants at risk Icosabutate 300mg oral capsule taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily	Icosabutate 600mg n=95 participants at risk Icosabutate 600mg oral capsules taken once daily for 52 weeks Icosabutate: Icosabutate oral capsule once daily
Infections and infestations Cellulitis	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	2.1% 2/95 • Number of events 2 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Infections and infestations Coronavirus infection	1.1% 1/91 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/92 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/95 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Infections and infestations Diverticulitis	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Infections and infestations Pneumonia	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Infections and infestations Sepsis	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Infections and infestations Septic shock	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Gastrointestinal disorders Abdominal pain	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/92 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/95 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Gastrointestinal disorders Diarrhea	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/92 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/95 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Infections and infestations Intra-abdominal hematoma	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/92 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/95 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Gastrointestinal disorders Pancreatitis acute	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Nervous system disorders Transient ischemic attack	1.1% 1/91 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Nervous system disorders Spinal claudication	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Cardiac disorders Angina pectoris	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Immune system disorders Food allergy	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/92 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/95 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Injury, poisoning and procedural complications Post-procedural hematoma	1.1% 1/91 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/95 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Investigations Coronavirus test positive	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	1.1% 1/91 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/95 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Renal and urinary disorders Acute kidney injury	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Reproductive system and breast disorders Ovarian cyst	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).
Vascular disorders Vasculitis	0.00% 0/91 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	0.00% 0/92 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).	1.1% 1/95 • Number of events 1 • AEs, which included clinical laboratory test variables, were monitored and documented from the time the patient signed the ICF until Visit 10 (Week 54) or the Early Termination visit (if applicable).