Trial Outcomes & Findings for Study of Safety and Tolerability of CFZ533 in Patients With Sjögren's Syndrome (NCT NCT04541589)

Last Updated: 2025-10-16

Results Overview

An AE was defined as any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a participant. TEAE included all AEs up to the last dose date plus 14 weeks or the end of the entire study (including the safety follow-up period), whichever occurred earlier. A patient with multiple severity ratings for an AE was only counted under the maximum rating. Additionally, a patient with multiple occurrences of an event was counted only once. The severity of AEs was assessed using the Common Terminology Criteria for Adverse Events, with the following grading system: Mild: usually transient in nature and generally not interfering with normal activities; Moderate: sufficiently discomforting to interfere with normal activities; Severe: prevented normal activities. A serious adverse event (SAE) was defined as any AE that required medical intervention, hospitalization, or results in death, disability, or a birth defect.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

206 participants

Primary outcome timeframe

From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks

Results posted on

2025-10-16

Participant Flow

Participants who completed the core study (CCFZ533B2201, NCT03905525) and were deemed by the Investigator to clinically benefit from continued iscalimab therapy based upon response to therapy at the end of the treatment period of the core study were enrolled in this study

Participant milestones

Participant milestones
Measure	Arm 1: Iscalimab 600 mg Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Treatment Period STARTED	152	54
Treatment Period COMPLETED	133	47
Treatment Period NOT COMPLETED	19	7
Safety Follow-up Period STARTED	152	54
Safety Follow-up Period COMPLETED	143	49
Safety Follow-up Period NOT COMPLETED	9	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Iscalimab 600 mg Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Treatment Period Adverse Event	8	2
Treatment Period Physician Decision	3	1
Treatment Period Subject decision	7	4
Treatment Period Withdrawal by Subject	1	0
Safety Follow-up Period Adverse Event	2	1
Safety Follow-up Period Physician Decision	1	0
Safety Follow-up Period Subject decision	5	3
Safety Follow-up Period Withdrawal by Subject	1	1

Baseline Characteristics

Study of Safety and Tolerability of CFZ533 in Patients With Sjögren's Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Iscalimab 600 mg n=152 Participants Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg n=54 Participants Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.	Total n=206 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	126 Participants n=5 Participants	45 Participants n=7 Participants	171 Participants n=5 Participants
Age, Categorical >=65 years	26 Participants n=5 Participants	9 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Female	148 Participants n=5 Participants	53 Participants n=7 Participants	201 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	125 Participants n=5 Participants	45 Participants n=7 Participants	170 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Asian	16 Participants n=5 Participants	6 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks

Population: The Safety Set (SAF) included all participants who received at least one dose of study treatment. Participants were analyzed according to the actual treatment received.

Outcome measures

Outcome measures
Measure	Arm 1: Iscalimab 600 mg n=152 Participants Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg n=54 Participants Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Death	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Adverse event (all severities)	127 Participants	43 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Adverse Event- Mild	57 Participants	24 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Adverse Event- Moderate	62 Participants	17 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Adverse Event- Severe	8 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Serious Adverse Event	13 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Adverse Event leading to study medication discontinuation	8 Participants	2 Participants

SECONDARY outcome

Timeframe: Predose at Day 1, 113, 225, 337 and 421

Population: The pharmacokinetic set (PKS) included all participants who received at least one dose of iscalimab treatment and had quantifiable PK measurements of iscalimab. Number analysed refers to the number of participants with a quantifiable PK measurement at the specified time point

Free iscalimab concentration in plasma during the treatment (Ctrough) and follow-up (up to end of study) periods. Blood sample was collected at the specified timepoints to assess the concentration of free iscalimab. The baseline assessment of this extension study (Day 1) was identical to the last timepoint (FUP3/Week 60) of the core study (CCFZ533B2201).

Outcome measures

Outcome measures
Measure	Arm 1: Iscalimab 600 mg n=149 Participants Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg n=52 Participants Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Free Iscalimab Concentration in Plasma Day 225	126 microgram / mililiter Geometric Coefficient of Variation 104.7	50.3 microgram / mililiter Geometric Coefficient of Variation 57.0
Free Iscalimab Concentration in Plasma Day 1	3.56 microgram / mililiter Geometric Coefficient of Variation 372.2	451.8 microgram / mililiter Geometric Coefficient of Variation 0.751
Free Iscalimab Concentration in Plasma Day 113	125 microgram / mililiter Geometric Coefficient of Variation 62.7	56.9 microgram / mililiter Geometric Coefficient of Variation 54.0
Free Iscalimab Concentration in Plasma Day 337	138 microgram / mililiter Geometric Coefficient of Variation 69.3	62.6 microgram / mililiter Geometric Coefficient of Variation 63.3
Free Iscalimab Concentration in Plasma Day 421	4.47 microgram / mililiter Geometric Coefficient of Variation 533.7	350.4 microgram / mililiter Geometric Coefficient of Variation 0.336

SECONDARY outcome

Timeframe: 60 weeks

Population: The immunogenicity Set (IMS) included all subjects who received at least one dose of iscalimab treatment and had quantifiable immunogenicity measurements of iscalimab.

Number of participants with anti-iscalimab antibodies (ADA) in plasma at any time during the study. The baseline assessment of this extension study (Day 1) was identical to the last timepoint (FUP3/Week 60) of the core study (CCFZ533B2201).

Outcome measures

Outcome measures
Measure	Arm 1: Iscalimab 600 mg n=152 Participants Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg n=54 Participants Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Incidence of Anti-iscalimab Antibodies in Plasma	1 Participants	2 Participants

Adverse Events

Arm 1: Iscalimab 600 mg

Serious events: 13 serious events

Other events: 102 other events

Deaths: 0 deaths

Arm 2 - Iscalimab 300 mg

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Arm 1: Iscalimab 600 mg n=152 participants at risk Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg n=54 participants at risk Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Blood and lymphatic system disorders Febrile neutropenia	1.3% 2/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Blood and lymphatic system disorders Granulocytopenia	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Blood and lymphatic system disorders Neutropenia	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Eye disorders Glaucoma	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Gastrointestinal disorders Anal prolapse	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Hepatobiliary disorders Cholangitis	0.00% 0/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	1.9% 1/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Immune system disorders Food allergy	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations Bartholinitis	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations COVID-19	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations COVID-19 pneumonia	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Musculoskeletal and connective tissue disorders Sjogren's syndrome	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	1.9% 1/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Nervous system disorders Status epilepticus	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Psychiatric disorders Adjustment disorder with depressed mood	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Psychiatric disorders Depression	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.66% 1/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	0.00% 0/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.

Measure	Arm 1: Iscalimab 600 mg n=152 participants at risk Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).	Arm 2 - Iscalimab 300 mg n=54 participants at risk Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Blood and lymphatic system disorders Neutropenia	6.6% 10/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	3.7% 2/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Gastrointestinal disorders Diarrhoea	8.6% 13/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	7.4% 4/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
General disorders Pyrexia	5.3% 8/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	3.7% 2/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations COVID-19	25.7% 39/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	29.6% 16/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations Influenza	4.6% 7/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	13.0% 7/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations Nasopharyngitis	14.5% 22/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	16.7% 9/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations Oral herpes	4.6% 7/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	5.6% 3/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations Sinusitis	4.6% 7/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	5.6% 3/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations Upper respiratory tract infection	12.5% 19/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	9.3% 5/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Infections and infestations Urinary tract infection	10.5% 16/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	9.3% 5/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 9/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	9.3% 5/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Musculoskeletal and connective tissue disorders Back pain	3.3% 5/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	5.6% 3/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Musculoskeletal and connective tissue disorders Osteoarthritis	4.6% 7/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	5.6% 3/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Nervous system disorders Headache	5.9% 9/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	5.6% 3/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Cough	5.9% 9/152 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.	7.4% 4/54 • From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analysis were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.