CompletedNCT03905525TWINSSUpdated May 18, 2026Results posted

Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjogren's Syndrome

A Phase 2 interventional study of CFZ533 and Placebo in Sjögren Syndrome, sponsored by Novartis Pharmaceuticals. Completed at 71 sites in 23 countries. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2026-05-18.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 273
Allocation: Randomized
Ages: 18 Years to 100 Years
Sex: All

Study summary

This study was to evaluate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses of CFZ533 (iscalimab) in patients with Sjögren's Syndrome (SjS).

Read the detailed description

This study consisted of a 6-week screening, 2 treatment periods of 24 weeks each, and a follow-up period of 12 weeks. In Periods 1 and 2, thirteen (13) treatment administration visits were planned, including a weekly loading regimen (2 visits) at the start of each treatment period. One administration equaled to two subcutaneous (s.c.) injections.

This study included two distinct cohorts termed Cohort 1 and Cohort 2.

Cohort 1: subjects with moderate-to-severe systemic and symptomatic disease involvement.
Cohort 2: subjects with low systemic disease involvement but high symptom burden.

Conditions studied

Sjögren Syndrome

Browse trials for

Keywords

Sjögren Syndrome (SjS)
sicca syndrome
dryness
fatigue
autoimmune disease
European League Against Rheumatism (EULAR)
EULAR Sjögren syndrome disease activity index (ESSDAI)
EULAR Sjögren syndrome patient reported index (ESSPRI)
monoclonal antibody
anti-CD40
iscalimab (CFZ533)
TWINSS

In context

Sjogren's Syndrome

371 studies on the registry are indexed under Sjogren's Syndrome; 104 are open to participants now.

This study's enrollment of 273 is above the median of 50 across 244 interventional studies indexed under Sjogren's Syndrome.

Browse Sjogren's Syndrome studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 100 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria:

Both cohorts must have met all the following criteria:

Signed informed consent must be obtained prior to participation in the study
Male or female patient >= 18 years of age
Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2016)
Seropositive for anti-Ro/SSA antibodies
Stimulated whole salivary flow rate of >= 0.1 mL/min
Able to communicate well with the Investigator to understand and comply with the requirements of the study
Inclusion criteria specific for Cohort 1:
Screening ESSDAI value >= 5 within the following 8 organ domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematologic and biologic
- Patients with involvement of one or more of the remaining 4 domains are eligible but scores of these domains will not contribute to the assessment for eligibility for Cohort 1
- At selected sites participating in Cohort 2, patients who based on the above criterion 7, do not qualify for Cohort 1, should be further evaluated for Cohort 2
Screening ESSPRI score of >= 5
Inclusion criteria specific for Cohort 2:
Screening ESSDAI value \< 5 within 8 domains scored for inclusion criterion #7 Cohort 1
Screening ESSPRI fatigue subscore >= 5 or ESSPRI dryness subscore >= 5
Hypergammaglobulinemia defined by IgG greater than upper limit of normal (ULN) or lymphocytopenia (less than lower limit of normal (LLN)) or hypocomplementemia (low C3, or low C4 - when considered due to disease activity and not due to genetic factors)
Score of >= 30 on IDEEL symptom bother questionnaire at Screening

Exclusion Criteria:

Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness
Use of other investigational drugs within 5 half-lives of enrollment or within 30 days whichever is longer, or longer if required by local regulations
Prior treatment with any of the following within 6 months prior to randomization:
- B-cell depletors (e.g. rituximab, ianalumab) unless CD19+ B cell count have returned to ≥ 50 cells/µL
- abatacept
- anti-tumor necrosis factor alpha monoclonal anti-body
- intravenous/subcutaneous Ig; plasmapheresis; i.v. or oral cyclophosphamide
- i.v. or oral cyclosporine A
- any other immunosuppressants unless explicitly allowed in criterion #5
Use of steroids (predniso(lo)ne or equivalent corticosteroid) at dose > 10 mg/day
Use of steroids and synthetic DMARDS at inconsistent dose and within 3 months prior to randomization

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 273 participants (actual)

Study arms

Experimental
Cohort 1 / Arm A
3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Weeks 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
Drug: CFZ533
Experimental
Cohort 1 / Arm B
3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 300 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 300 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
Drug: CFZ533
Experimental
Cohort 1 / Arm C
3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, and 150 mg on Week 1 and Week 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 150 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
Drug: CFZ533
Placebo comparator
Cohort 1 / Arm D (Period 1)
Placebo treatment is administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.
Other: Placebo
Experimental
Cohort 1 / Arm D1 (Period 2)
Period 2: 3 weekly subcutaneous (s.c.) loading doses of 600 mg iscalimab on Week 24, 25 and 26. After Week 26 and up to Week 46 (last dose), iscalimab was administered bi-weekly at 600 mg.
Drug: CFZ533
Experimental
Cohort 2 / Arm E
3 weekly subcutaneous (s.c.) loading doses of iscalimab were 600 mg on Week 0, 1 and 2. From Week 2 and up to Week 46 (last dose), iscalimab was administered s.c. bi-weekly at 600 mg. To maintain blinding in Period 2, placebo was administered at Week 25.
Drug: CFZ533
Placebo comparator
Cohort 2 / Arm F (Period 1)
Placebo treatment was administered subcutaneous (s.c.) weekly for the first 3 doses, then bi-weekly from Week 2 to Week 22 in Period 1.
Other: Placebo
Experimental
Cohort 2 / Arm F1 (Period 2)
Period 2: 3 weekly subcutaneous (s.c.) loading doses of iscalimab: 600 mg on Week 24, and 300 mg on Week 25 and Week 26. After Week 26, iscalimab was administered s.c. bi-weekly at 300 mg.
Drug: CFZ533

Interventions

DrugCFZ533
Biological
Also known as: iscalimab
OtherPlacebo
liquid placebo for injections

What researchers measure

Primary outcomes

Cohort 1: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) Score From Baseline at 24 Weeks as Compared to Placebo
ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The total score may vary between 0-123. It is considered low activity an ESSDAI \< 5; moderate activity 5-13, and high activity if ESSDAI is \>= 14.
Time frame: Baseline, Week 24
Cohort 2: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) Score From Baseline at 24 Weeks as Compared to Placebo.
The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.
Time frame: Baseline, Week 24

Secondary outcomes

Cohort 1: Change From Baseline in ESSPRI at Week 24
The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.
Time frame: Baseline, Week 24
Cohort 1: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24
The FACIT F (Functional Assessment of Chronic Illness Therapy-Fatigue) is a validated 13 item patient reported outcome measure assessing fatigue and its impact on daily functioning over the past 7 days, with total scores ranging from 0 to 52, where higher scores indicate less fatigue.
Time frame: Baseline, 24 weeks
Cohort 1: Change From Baseline in Physician Global Assessment (PhGA) at Week 24
Physician's global assessment (PhGA) of disease activity was performed using a Visual Analog Scale (VAS) - an unnumbered 100 mm horizontal line ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100). The assessment of patient's condition on the day is made by placing a vertical mark across the line.
Time frame: Baseline, 24 weeks
Cohort 2: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24
The FACIT F (Functional Assessment of Chronic Illness Therapy-Fatigue) is a validated 13 item patient reported outcome measure assessing fatigue and its impact on daily functioning over the past 7 days, with total scores ranging from 0 to 52, where higher scores indicate less fatigue.
Time frame: Baseline, 24 weeks
Cohort 2: Change From Baseline in Physician Global Assessment (PhGA) at Week 24
Physician's global assessment (PhGA) of disease activity was performed using a Visual Analog Scale (VAS) - an unnumbered 100 mm horizontal line ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100). The assessment of patient's condition on the day is made by placing a vertical mark across the line.
Time frame: Baseline, 24 weeks
Cohort 2: Change From Baseline in ESSDAI at Week 24
ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The final score may vary between 0-123. It is considered low activity an ESSDAI \< 5; moderate activity 5-13, and high activity if ESSDAI is \>= 14.
Time frame: Baseline, week 24
Cohort 2: Proportion of Subjects With at Least 12 Points Improvement Measured by Score of Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire Symptom Bother Module at Week 24.
The Impact of Dry Eye on Everyday Life (IDEEL) questionnaire is a comprehensive dry eye specific questionnaire to evaluate treatment satisfaction, symptom-related bother and impact on daily life in a population with dry eye. This study only utilized the Dry Eye Symptom-Bother module. The Dry Eye Symptom-Bother module of IDEEL is composed of a single dimension (20 items). A 4-point Likert-like scale is used: from "not at all" to "very much". Patients could also answer "I did not have this symptom / Not applicable". One item is scored on a 5-point Likert-like scale from "none of the time" to "all of the time". The range for the symptom-bother score is 0 to 100, with higher scores indicating greater symptom bother.
Time frame: Baseline, Week 24
Cohort 1: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) up to Week 24
The distribution of adverse events in Treatment Period 1 was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) up to Week 24 (Period 1) is presented by actual treatment during Period 1, with data from separate cohort for the CFZ533 600mg and for the Placebo groups: CFZ533 600 mg, CFZ533 300 mg, CFZ533 150 mg and placebo.
Time frame: Up to Week 24
Cohort 1: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) in All Study Periods
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg - CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 600 mg 24 Weeks arm includes only patients from Placebo - CFZ533 600 mg arm, who took at least one CFZ533 600 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week 24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm, and subjects from CFZ533 150 mg - CFZ533 150 mg and CFZ533 300 mg - CFZ533 300 mg arms but only took the first or the first two loading dose(s) in period 1.
Time frame: up to 14 weeks following the last dose of study treatment, up to maximum Week 60
Cohort 2: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) up to Week 24
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) up to Week 24 (Period 1) is presented by actual treatment during Period 1, with data from separate cohort for the CFZ533 600mg and for the Placebo groups: CFZ533 600 mg and placebo.
Time frame: Up to Week 24
Cohort 2: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) in All Study Periods
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg - CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 300 mg 24 Weeks includes only patients from Placebo - CFZ533 300 mg arm, who received Placebo in Period 1, and either took CFZ533 600 mg loading dose + at least two CFZ533 300 mg subsequent doses in Period 2 or missed CFZ533 600 mg loading dose and took at least one CFZ533 300 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm.
Time frame: up to 14 weeks following the last dose of study treatment, up to maximum Week 60
Cohort 1: Change From Baseline in Serum Free Light Kappa (FLCκ) Chains Levels
Serum samples for free light kappa (FLCκ) chains were collected and analyzed.
Time frame: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 40, Week 48 (End Treatment Period 2), FUP2 (Week 56), FUP 3 (Week 60)
Cohort 2: Change From Baseline in Serum Free Light Kappa (FLCκ) Chains Levels
Serum samples for free light kappa (FLCκ) chains were collected and analyzed.
Time frame: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 40, Week 48 (End Treatment Period 2), FUP2 (Week 56), FUP 3 (Week 60)
Cohort 1: Change From Baseline in Immunoglobulin G (IgG) Levels
Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Cohort 2: Change From Baseline in Immunoglobulin G (IgG) Levels
Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Cohort 1: Change From Baseline in Immunoglobulin M (IgM) Levels
Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Cohort 2: Change From Baseline in Immunoglobulin M (IgM) Levels
Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Cohort 1: Change From Baseline in Plasma CXCL-13 Levels
Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.
Time frame: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 48 (End Treatment Period 2), FUP 3 (Week 60)
Cohort 2: Change From Baseline in Plasma CXCL-13 Levels
Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.
Time frame: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 48 (End Treatment Period 2), FUP 3 (Week 60)

Results

Posted May 18, 2026

Participant flow

The study was conducted at 71 sites in 23 countries. Argentina (2), Australia (1), Austria (2), Brazil (3), Canada (3), Chile (5), Colombia (3), France (5), Germany (4), Greece (1), Hungary (3), Israel (3), Italy (3), Japan (5), Republic of Korea (1), Netherlands (2), Portugal (4), Romania (2), Russia (6), Sweden (1), Turkey (1), United Kingdom (3), United States (8).

Period 1 (up to Week 24): Cohorts 1&2

Participant flow — Period 1 (up to Week 24): Cohorts 1&2
Milestone	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg
Started	43	44	43	43	50	50
Full analysis set (fas)	43	44	43	43	50	50
Safety set (saf)	43	44	43	43	50	50
Continued to treatment period 2	41	42	41	39	45	48
Completed	41	42	41	39	44	48
Not completed	2	2	2	4	6	2
Withdrew: Adverse event	1	1	2	4	3	1
Withdrew: Lost to follow-up	1	0	0	0	0	0
Withdrew: Physician decision	0	1	0	0	0	0
Withdrew: Subject decision	0	0	0	0	3	1

Period 2 (up to Week 48): Cohorts 1&2

Participant flow — Period 2 (up to Week 48): Cohorts 1&2
Milestone	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (From Week 24)	Cohort 2/Arm E: CFZ533 600 mg	Cohort 2 / Arm F1 (Period 2): CFZ533 300mg
Started	42	41	39	41	48	45
Continued to post-treatment follow-up period	42	40	39	41	46	45
Completed	38	36	39	39	41	44
Not completed	4	5	0	2	7	1
Withdrew: Adverse event	1	1	0	0	1	1
Withdrew: Death	0	1	0	0	1	0
Withdrew: Physician decision	0	1	0	0	0	0
Withdrew: Subject decision	3	1	0	2	4	0
Withdrew: Withdrawal of consent	0	1	0	0	0	0
Withdrew: Protocol deviation	0	0	0	0	1	0

Outcome measures

PrimaryCohort 1: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) Score From Baseline at 24 Weeks as Compared to Placebo

ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The total score may vary between 0-123. It is considered low activity an ESSDAI \< 5; moderate activity 5-13, and high activity if ESSDAI is \>= 14.

Time frame:: Baseline, Week 24
Reported as:: Least squares mean · Unit on a scale

Cohort 1: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) Score From Baseline at 24 Weeks as Compared to Placebo
Unit on a scale	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg
Cohort 1: Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) Score From Baseline at 24 Weeks as Compared to Placebo	-4.0 ± 0.73	-7.0 ± 0.70	-5.4 ± 0.71	-6.9 ± 0.73

Statistical analysis

Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm C: CFZ533 150 mg · Mixed Models Analysis · p = 0.0025 · Ls mean difference cfz533-placebo: -3.0 · 95% CI -4.9 to -1.1MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm B: CFZ533 300 mg · Mixed Models Analysis · p = 0.1578 · Ls mean difference cfz533-placebo: -1.4 · 95% CI -3.3 to 0.5MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm A: CFZ533 600 mg · Mixed Models Analysis · p = 0.0037 · Ls mean difference cfz533-placebo: -2.9 · 95% CI -4.9 to -1.0MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.

PrimaryCohort 2: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) Score From Baseline at 24 Weeks as Compared to Placebo.

The ESSPRI is a self-evaluation index for measuring symptoms including pain, fatigue and dryness. Each symptom was measured with a single 0 (no symptoms) to 10 (severe symptoms) numerical scale and the final ESSPRI score is calculated by averaging these domains with a maximum severity score of 10.

Time frame:: Baseline, Week 24
Reported as:: Least squares mean · Unit on a scale

Cohort 2: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) Score From Baseline at 24 Weeks as Compared to Placebo.
Unit on a scale	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg
Cohort 2: Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) Score From Baseline at 24 Weeks as Compared to Placebo.	-1.21 ± 0.271	-1.79 ± 0.258

Statistical analysis

Cohort 2/Arm F: Placebo vs Cohort 2/Arm E: CFZ533 600 mg · Mixed Models Analysis · p = 0.1210 · Ls mean difference cfz533-placebo: -0.57 · 95% CI -1.30 to 0.15MMRM that includes treatment, visit, treatment by visit interaction and region as factors and baseline value of corresponding parameter as continuous covariates.

SecondaryCohort 1: Change From Baseline in ESSPRI at Week 24

Time frame:: Baseline, Week 24
Reported as:: Least squares mean · Unit on a scale

Cohort 1: Change From Baseline in ESSPRI at Week 24
Unit on a scale	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg
Cohort 1: Change From Baseline in ESSPRI at Week 24	-1.3 ± 0.31	-1.8 ± 0.30	-1.6 ± 0.31	-1.8 ± 0.31

Statistical analysis

Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm C: CFZ533 150 mg · Mixed Models Analysis · p = 0.2078 · Ls mean difference cfz533-placebo: -0.5 · 95% CI -1.4 to 0.3MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm B: CFZ533 300 mg · Mixed Models Analysis · p = 0.5132 · Ls mean difference cfz533-placebo: -0.3 · 95% CI -1.1 to 0.6MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm A: CFZ533 600 mg · Mixed Models Analysis · p = 0.1998 · Ls mean difference cfz533-placebo: -0.5 · 0.1998% CI -1.4 to 0.3MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.

SecondaryCohort 1: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24

The FACIT F (Functional Assessment of Chronic Illness Therapy-Fatigue) is a validated 13 item patient reported outcome measure assessing fatigue and its impact on daily functioning over the past 7 days, with total scores ranging from 0 to 52, where higher scores indicate less fatigue.

Time frame:: Baseline, 24 weeks
Reported as:: Least squares mean · Unit on a scale

Cohort 1: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24
Unit on a scale	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg
Cohort 1: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24	7.0 ± 1.48	8.6 ± 1.45	8.0 ± 1.47	10.3 ± 1.50

Statistical analysis

Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm C: CFZ533 150 mg · Mixed Models Analysis · p = 0.4363 · Ls mean difference cfz533-placebo: 1.6 · 95% CI -2.4 to 5.6MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm B: CFZ533 300 mg · Mixed Models Analysis · p = 0.6181 · Ls mean difference cfz533-placebo: 1.0 · 95% CI -3.0 to 5.0MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm A: CFZ533 600 mg · Mixed Models Analysis · p = 0.1050 · Ls mean difference cfz533-placebo: 3.3 · 95% CI -0.7 to 7.3MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.

SecondaryCohort 1: Change From Baseline in Physician Global Assessment (PhGA) at Week 24

Physician's global assessment (PhGA) of disease activity was performed using a Visual Analog Scale (VAS) - an unnumbered 100 mm horizontal line ranging from "no disease activity" (score 0) to "maximal disease activity" (score 100). The assessment of patient's condition on the day is made by placing a vertical mark across the line.

Time frame:: Baseline, 24 weeks
Reported as:: Least squares mean · Unit on a scale

Cohort 1: Change From Baseline in Physician Global Assessment (PhGA) at Week 24
Unit on a scale	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 1/Arm B: CFZ533 300 mg
Cohort 1: Change From Baseline in Physician Global Assessment (PhGA) at Week 24	-23.9 ± 2.94	-31.6 ± 2.83	-27.0 ± 2.87	-30.8 ± 3.00

Statistical analysis

Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm C: CFZ533 150 mg · Mixed Models Analysis · p = 0.0561 · Ls mean difference cfz533-placebo: -7.7 · 95% CI -15.6 to 0.2MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm A: CFZ533 600 mg · Mixed Models Analysis · p = 0.4433 · Ls mean difference cfz533-placebo: -3.1 · 95% CI -11.0 to 4.8MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.
Cohort 1 / Arm D (Period 1): Placebo vs Cohort 1/Arm B: CFZ533 300 mg · Mixed Models Analysis · p = 0.0974 · Ls mean difference cfz533-placebo: -6.9 · 95% CI -15.0 to 1.3MMRM that includes treatment, visit, treatment by visit interaction, stratification factor baseline ESSDAI score (\< 10 or \>= 10 based on weighted scores), and region as factors and baseline value of corresponding parameter as continuous covariates.

SecondaryCohort 2: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24

Time frame:: Baseline, 24 weeks
Reported as:: Least squares mean · Unit on a scale

Cohort 2: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24
Unit on a scale	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg
Cohort 2: Change From Baseline in Score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Questionnaire at Week 24	5.7 ± 1.32	7.3 ± 1.25

Statistical analysis

Cohort 2/Arm F: Placebo vs Cohort 2/Arm E: CFZ533 600 mg · Mixed Models Analysis · p = 0.3675 · Ls mean difference cfz533-placebo: 1.6 · 95% CI -1.9 to 5.1MMRM that includes treatment, visit, treatment by visit interaction and region as factors and baseline value of corresponding parameter as continuous covariates.

SecondaryCohort 2: Change From Baseline in Physician Global Assessment (PhGA) at Week 24

Time frame:: Baseline, 24 weeks
Reported as:: Least squares mean · Unit on a scale

Cohort 2: Change From Baseline in Physician Global Assessment (PhGA) at Week 24
Unit on a scale	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg
Cohort 2: Change From Baseline in Physician Global Assessment (PhGA) at Week 24	-10.4 ± 2.37	-15.8 ± 2.29

Statistical analysis

Cohort 2/Arm F: Placebo vs Cohort 2/Arm E: CFZ533 600 mg · Mixed Models Analysis · p = 0.1014 · Ls mean difference cfz533-placebo: -5.4 · 95% CI -11.8 to 1.1MMRM that includes treatment, visit, treatment by visit interaction and region as factors and baseline value of corresponding parameter as continuous covariates.

SecondaryCohort 2: Change From Baseline in ESSDAI at Week 24

ESSDAI is a validated disease outcome measure for SjS that contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score. The domains (weights) are as follows: constitutional (3), lymphadenopathy (4), glandular (2), articular (2), cutaneous (3), pulmonary (5), renal (5), muscular (6), peripheral nervous system (PNS) (5), central nervous system (CNS) (5), hematological (2) and biological (1). The final score may vary between 0-123. It is considered low activity an ESSDAI \< 5; moderate activity 5-13, and high activity if ESSDAI is \>= 14.

Time frame:: Baseline, week 24
Reported as:: Least squares mean · Unit on a scale

Cohort 2: Change From Baseline in ESSDAI at Week 24
Unit on a scale	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg
Cohort 2: Change From Baseline in ESSDAI at Week 24	0.2 ± 0.33	-0.3 ± 0.32

Statistical analysis

Cohort 2/Arm F: Placebo vs Cohort 2/Arm E: CFZ533 600 mg · Mixed Models Analysis · p = 0.2694 · Ls mean difference cfz533-placebo: -0.5 · 95% CI -1.4 to 0.4MMRM that includes treatment, visit, treatment by visit interaction and region as factors and baseline value of corresponding parameter as continuous covariates.

SecondaryCohort 2: Proportion of Subjects With at Least 12 Points Improvement Measured by Score of Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire Symptom Bother Module at Week 24.

The Impact of Dry Eye on Everyday Life (IDEEL) questionnaire is a comprehensive dry eye specific questionnaire to evaluate treatment satisfaction, symptom-related bother and impact on daily life in a population with dry eye. This study only utilized the Dry Eye Symptom-Bother module. The Dry Eye Symptom-Bother module of IDEEL is composed of a single dimension (20 items). A 4-point Likert-like scale is used: from "not at all" to "very much". Patients could also answer "I did not have this symptom / Not applicable". One item is scored on a 5-point Likert-like scale from "none of the time" to "all of the time". The range for the symptom-bother score is 0 to 100, with higher scores indicating greater symptom bother.

Time frame:: Baseline, Week 24
Reported as:: Count of participants · Participants

Cohort 2: Proportion of Subjects With at Least 12 Points Improvement Measured by Score of Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire Symptom Bother Module at Week 24.
Participants	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg
Cohort 2: Proportion of Subjects With at Least 12 Points Improvement Measured by Score of Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire Symptom Bother Module at Week 24.	20	24

Statistical analysis

Cohort 2/Arm F: Placebo vs Cohort 2/Arm E: CFZ533 600 mg · Fisher Exact · p = 0.5459 · Clopper-pearson method: 8.0 · 95% CI -11.4 to 27.4Difference CFZ533-Placebo

SecondaryCohort 1: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) up to Week 24

The distribution of adverse events in Treatment Period 1 was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) up to Week 24 (Period 1) is presented by actual treatment during Period 1, with data from separate cohort for the CFZ533 600mg and for the Placebo groups: CFZ533 600 mg, CFZ533 300 mg, CFZ533 150 mg and placebo.

Time frame:: Up to Week 24
Reported as:: Count of participants · Participants

Cohort 1: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) up to Week 24
Participants	Cohort 1: Placebo	Cohort 1: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1: CFZ533 600 mg
Death	0	0	0	0
Adverse Event	31	38	32	35
Serious Adverse Event	1	1	3	4
AE leading to study medication discontinuation	1	1	1	5

SecondaryCohort 1: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) in All Study Periods

The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg - CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 600 mg 24 Weeks arm includes only patients from Placebo - CFZ533 600 mg arm, who took at least one CFZ533 600 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week 24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm, and subjects from CFZ533 150 mg - CFZ533 150 mg and CFZ533 300 mg - CFZ533 300 mg arms but only took the first or the first two loading dose(s) in period 1.

Time frame:: up to 14 weeks following the last dose of study treatment, up to maximum Week 60
Reported as:: Count of participants · Participants

Cohort 1: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) in All Study Periods
Participants	Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (From Week 24)	Cohort 1/Arm C: CFZ533 150 mg (48 Weeks)	Cohort 1/Arm B: CFZ533 300 mg (48 Weeks)	Cohort 1/Arm A: CFZ533 600 mg (48 Weeks)	Any CFZ533 600 mg	Any CFZ533
Death	0	0	1	0	0	1
Adverse Event	34	40	38	43	77	155
Serious Adverse Event	4	6	6	6	10	22
AE leading to study medication discontinuation	0	2	3	5	5	10

SecondaryCohort 2: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) up to Week 24

Time frame:: Up to Week 24
Reported as:: Count of participants · Participants

Cohort 2: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) up to Week 24
Participants	Cohort 2: Placebo	Cohort 2: CFZ533 600 mg
Death	0	0
Adverse Event	32	41
Serious Adverse Event	2	2
AE leading to study medication discontinuation	3	1

SecondaryCohort 2: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) in All Study Periods

The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Analyses of data in the Safety Set (SAF) for period 2/3 or overall study is presented by actual treatment sequence during periods 1 and 2, where the CFZ533 600 mg - CFZ533 600 mg sequence included data from patients in separate cohort. CFZ533 300 mg 24 Weeks includes only patients from Placebo - CFZ533 300 mg arm, who received Placebo in Period 1, and either took CFZ533 600 mg loading dose + at least two CFZ533 300 mg subsequent doses in Period 2 or missed CFZ533 600 mg loading dose and took at least one CFZ533 300 mg dose in Period 2 (Patients who received Placebo in Period 1 and discontinued before Week24 are not included). CFZ533 600 mg 48 Weeks arm includes all subjects from CFZ533 600 mg - CFZ533 600 mg arm.

Time frame:: up to 14 weeks following the last dose of study treatment, up to maximum Week 60
Reported as:: Count of participants · Participants

Cohort 2: Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) in All Study Periods
Participants	Cohort 2 / Arm F1 (Period 2): CFZ533 300mg (From Week 24)	Cohort 2/Arm E: CFZ533 600 mg (48 Weeks)	Any CFZ533
Death	0	1	1
Adverse Event	35	44	79
Serious Adverse Event	5	6	11
AE leading to study medication discontinuation	0	3	3

SecondaryCohort 1: Change From Baseline in Serum Free Light Kappa (FLCκ) Chains Levels

Serum samples for free light kappa (FLCκ) chains were collected and analyzed.

Time frame:: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 40, Week 48 (End Treatment Period 2), FUP2 (Week 56), FUP 3 (Week 60)
Reported as:: Least squares mean · mg/L

Cohort 1: Change From Baseline in Serum Free Light Kappa (FLCκ) Chains Levels
mg/L	Cohort 1 - Arms D/D1 (Placebo - CFZ533 600 mg)	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg
Week 4	-1.9 ± 1.85	-7.2 ± 1.86	-5.4 ± 1.86	-5.5 ± 1.92
Week 12	-1.1 ± 2.02	-9.7 ± 2.01	-8.8 ± 2.03	-8.6 ± 2.08
Week 24 (End Treatment Period 1)	0.2 ± 2.26	-9.9 ± 2.26	-10.1 ± 2.28	-11.3 ± 2.35
Week 32	-8.6 ± 2.17	-11.8 ± 2.17	-11.1 ± 2.18	-8.9 ± 2.26
Week 40	-11.3 ± 2.05	-12.0 ± 2.06	-13.5 ± 2.07	-11.0 ± 2.13
Week 48 (End Treatment Period 2)	-13.9 ± 2.25	-12.5 ± 2.25	-13.1 ± 2.27	-11.6 ± 2.32
FUP2 (Week 56)	-11.8 ± 2.03	-5.6 ± 1.99	-8.9 ± 2.01	-12.4 ± 2.06
FUP 3 (Week 60)	-9.3 ± 2.07	-3.9 ± 2.04	-4.1 ± 2.07	-10.3 ± 2.11

SecondaryCohort 2: Change From Baseline in Serum Free Light Kappa (FLCκ) Chains Levels

Serum samples for free light kappa (FLCκ) chains were collected and analyzed.

Time frame:: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 40, Week 48 (End Treatment Period 2), FUP2 (Week 56), FUP 3 (Week 60)
Reported as:: Least squares mean · mg/L

Cohort 2: Change From Baseline in Serum Free Light Kappa (FLCκ) Chains Levels
mg/L	Cohort 2: Placebo - CFZ533 300 mg	Cohort 2: CFZ533 600 mg - CFZ533 600 mg
Week 4	0.3 ± 0.92	-4.3 ± 0.87
Week 12	0.1 ± 1.10	-7.2 ± 1.06
Week 24 (End Treatment Period 1)	-0.2 ± 0.90	-9.9 ± 0.86
Week 32	-6.0 ± 0.93	-10.5 ± 0.89
Week 40	-7.8 ± 0.93	-9.9 ± 0.91
Week 48 (End Treatment Period 2)	-9.3 ± 0.95	-11.9 ± 0.92
FUP2 (Week 56)	-6.1 ± 1.00	-11.7 ± 0.99
FUP 3 (Week 60)	-1.9 ± 1.11	-11.0 ± 1.09

SecondaryCohort 1: Change From Baseline in Immunoglobulin G (IgG) Levels

Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.

Time frame:: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Reported as:: Least squares mean · g/L

Cohort 1: Change From Baseline in Immunoglobulin G (IgG) Levels
g/L	Cohort 1 - Arms D/D1 (Placebo - CFZ533 600 mg)	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg
Week 4	0.1 ± 0.31	-0.9 ± 0.31	-0.6 ± 0.31	-0.8 ± 0.32
Week 8	0.0 ± 0.31	-1.1 ± 0.31	-1.0 ± 0.31	-1.4 ± 0.31
Week 12	0.4 ± 0.28	-1.7 ± 0.27	-1.7 ± 0.28	-1.5 ± 0.28
Week 16	0.4 ± 0.39	-1.8 ± 0.39	-2.2 ± 0.39	-2.0 ± 0.40
Week 20	0.1 ± 0.35	-2.4 ± 0.34	-2.3 ± 0.35	-2.1 ± 0.36
Week 24 (End Treatment Period 1)	0.0 ± 0.36	-2.1 ± 0.35	-2.5 ± 0.36	-2.5 ± 0.36
Week 28	-0.9 ± 0.39	-2.3 ± 0.38	-2.7 ± 0.39	-2.9 ± 0.39
Week 32	-1.3 ± 0.36	-2.6 ± 0.36	-3.0 ± 0.36	-3.3 ± 0.37
Week 40	-2.3 ± 0.36	-2.7 ± 0.36	-3.2 ± 0.36	-3.1 ± 0.36
Week 48 (End Treatment Period 2)	-3.0 ± 0.40	-2.8 ± 0.40	-3.7 ± 0.41	-3.4 ± 0.40
FUP1 (Week 52)	-3.6 ± 0.47	-2.9 ± 0.46	-3.8 ± 0.47	-3.7 ± 0.46
FUP2 (Week 56)	-3.0 ± 0.45	-2.0 ± 0.43	-3.2 ± 0.44	-3.9 ± 0.44
FUP 3 (Week 60)	-2.9 ± 0.47	-1.2 ± 0.46	-1.9 ± 0.47	-3.3 ± 0.46

SecondaryCohort 2: Change From Baseline in Immunoglobulin G (IgG) Levels

Plasma samples for Immunoglobulin G (IgG) were collected and analyzed.

Time frame:: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Reported as:: Least squares mean · g/L

Cohort 2: Change From Baseline in Immunoglobulin G (IgG) Levels
g/L	Cohort 2: Placebo - CFZ533 300 mg	Cohort 2: CFZ533 600 mg - CFZ533 600 mg
Week 4	-0.8 ± 0.25	-0.8 ± 0.24
Week 8	-0.5 ± 0.28	-1.9 ± 0.27
Week 12	-0.4 ± 0.30	-2.5 ± 0.29
Week 16	-0.6 ± 0.32	-3.0 ± 0.30
Week 20	-0.7 ± 0.32	-3.2 ± 0.30
Week 24 (End Treatment Period 1)	0.0 ± 0.42	-3.6 ± 0.40
Week 28	-1.3 ± 0.38	-4.2 ± 0.36
Week 32	-1.5 ± 0.35	-4.1 ± 0.34
Week 40	-2.6 ± 0.43	-4.9 ± 0.42
Week 48 (End Treatment Period 2)	-3.2 ± 0.43	-4.5 ± 0.43
FUP1 (Week 52)	-4.0 ± 0.45	-5.0 ± 0.44
FUP2 (Week 56)	-3.3 ± 0.46	-4.8 ± 0.45
FUP 3 (Week 60)	-2.4 ± 0.46	-4.5 ± 0.45

SecondaryCohort 1: Change From Baseline in Immunoglobulin M (IgM) Levels

Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.

Time frame:: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Reported as:: Least squares mean · g/L

Cohort 1: Change From Baseline in Immunoglobulin M (IgM) Levels
g/L	Cohort 1 - Arms D/D1 (Placebo - CFZ533 600 mg)	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg
Week 4	0.0 ± 0.04	-0.1 ± 0.04	-0.1 ± 0.04	-0.1 ± 0.04
Week 8	0.0 ± 0.04	-0.2 ± 0.04	-0.3 ± 0.04	-0.2 ± 0.04
Week 12	0.0 ± 0.04	-0.2 ± 0.04	-0.3 ± 0.04	-0.2 ± 0.04
Week 16	0.0 ± 0.05	-0.2 ± 0.05	-0.3 ± 0.05	-0.3 ± 0.05
Week 20	0.0 ± 0.05	-0.2 ± 0.05	-0.4 ± 0.05	-0.3 ± 0.05
Week 24 (End Treatment Period 1)	0.0 ± 0.06	-0.2 ± 0.06	-0.4 ± 0.06	-0.3 ± 0.06
Week 28	-0.1 ± 0.05	-0.2 ± 0.05	-0.4 ± 0.05	-0.3 ± 0.05
Week 32	-0.2 ± 0.06	-0.2 ± 0.06	-0.4 ± 0.06	-0.3 ± 0.06
Week 40	-0.3 ± 0.06	-0.2 ± 0.06	-0.4 ± 0.06	-0.3 ± 0.06
Week 48 (End Treatment Period 2)	-0.3 ± 0.06	-0.2 ± 0.06	-0.4 ± 0.06	-0.3 ± 0.06
FUP1 (Week 52)	-0.4 ± 0.05	-0.2 ± 0.05	-0.4 ± 0.05	-0.3 ± 0.05
FUP2 (Week 56)	-0.3 ± 0.05	0.0 ± 0.05	-0.1 ± 0.05	-0.3 ± 0.05
FUP 3 (Week 60)	-0.2 ± 0.07	-0.1 ± 0.06	0.0 ± 0.07	-0.2 ± 0.06

SecondaryCohort 2: Change From Baseline in Immunoglobulin M (IgM) Levels

Plasma samples for Immunoglobulin M (IgM) were collected and analyzed.

Time frame:: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 (End Treatment Period 1), Week 28, Week 32, Week 40, Week 48 (End Treatment Period 2), FUP1 (Week 52), FUP2 (Week 56), FUP 3 (Week 60)
Reported as:: Least squares mean · g/L

Cohort 2: Change From Baseline in Immunoglobulin M (IgM) Levels
g/L	Cohort 2: Placebo - CFZ533 300 mg	Cohort 2: CFZ533 600 mg - CFZ533 600 mg
Week 4	0.0 ± 0.03	-0.1 ± 0.03
Week 8	0.0 ± 0.04	-0.3 ± 0.04
Week 12	0.0 ± 0.05	-0.3 ± 0.05
Week 16	-0.1 ± 0.06	-0.4 ± 0.05
Week 20	-0.1 ± 0.06	-0.4 ± 0.06
Week 24 (End Treatment Period 1)	0.0 ± 0.06	-0.4 ± 0.06
Week 28	-0.2 ± 0.06	-0.5 ± 0.06
Week 32	-0.2 ± 0.07	-0.5 ± 0.06
Week 40	-0.3 ± 0.07	-0.5 ± 0.07
Week 48 (End Treatment Period 2)	-0.3 ± 0.07	-0.5 ± 0.07
FUP1 (Week 52)	-0.3 ± 0.06	-0.5 ± 0.06
FUP2 (Week 56)	-0.2 ± 0.72	-0.5 ± 0.07
FUP 3 (Week 60)	-0.1 ± 0.08	-0.5 ± 0.08

SecondaryCohort 1: Change From Baseline in Plasma CXCL-13 Levels

Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.

Time frame:: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 48 (End Treatment Period 2), FUP 3 (Week 60)
Reported as:: Least squares mean · pg/mL

Cohort 1: Change From Baseline in Plasma CXCL-13 Levels
pg/mL	Cohort 1 - Arms D/D1 (Placebo - CFZ533 600 mg)	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg
Week 4	-19.0 ± 12.51	-78.7 ± 12.84	-88.4 ± 12.74	-77.0 ± 13.23
Week 12	-23.8 ± 12.42	-99.4 ± 12.56	-77.4 ± 12.59	-108.5 ± 12.69
Week 24 (End Treatment Period 1)	-15.6 ± 13.78	-89.7 ± 14.08	-83.2 ± 13.98	-111.6 ± 14.26
Week 32	-102.5 ± 17.37	-80.5 ± 17.68	-78.3 ± 18.21	-71.3 ± 19.02
Week 48 (End Treatment Period 2)	-116.6 ± 11.73	-75.9 ± 12.02	-89.7 ± 12.26	-118.7 ± 12.15
FUP 3 (Week 60)	-73.9 ± 21.62	24.4 ± 22.10	-22.4 ± 22.55	-68.7 ± 22.24

SecondaryCohort 2: Change From Baseline in Plasma CXCL-13 Levels

Plasma samples for Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1) were collected and analyzed.

Time frame:: Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 48 (End Treatment Period 2), FUP 3 (Week 60)
Reported as:: Least squares mean · pg/mL

Cohort 2: Change From Baseline in Plasma CXCL-13 Levels
pg/mL	Cohort 2: Placebo - CFZ533 300 mg	Cohort 2: CFZ533 600 mg - CFZ533 600 mg
Week 4	-9.0 ± 8.50	-88.7 ± 7.99
Week 12	8.8 ± 16.16	-97.8 ± 15.55
Week 24 (End Treatment Period 1)	-27.4 ± 7.19	-114.1 ± 6.81
Week 32	-97.2 ± 7.03	-116.1 ± 6.65
Week 48 (End Treatment Period 2)	-99.2 ± 6.84	-107.8 ± 6.81
FUP 3 (Week 60)	-10.9 ± 10.76	-66.5 ± 10.53

Adverse events

Collected over On-treatment adverse events and deaths were reported from first dose of study treatment to 14 weeks after last dose of study medication, up to Week 60.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort 1 / Arm D (Period 1): Placebo	0/43 (0%)	1/43 (2.3%)	18/43 (41.9%)
Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (From Week 24)	0/41 (0%)	4/41 (9.8%)	28/41 (68.3%)
Cohort 1/Arm C: CFZ533 150 mg	0/44 (0%)	6/44 (13.6%)	33/44 (75%)
Cohort 1/Arm B: CFZ533 300 mg	1/42 (2.4%)	6/42 (14.3%)	34/42 (81%)
Cohort 1/Arm A: CFZ533 600 mg	0/44 (0%)	6/44 (13.6%)	34/44 (77.3%)
Cohort 2/Arm F: Placebo	0/50 (0%)	2/50 (4%)	27/50 (54%)
Cohort 2 / Arm F1 (Period 2): CFZ533 300mg	0/44 (0%)	5/44 (11.4%)	32/44 (72.7%)
Cohort 2/Arm E: CFZ533 600 mg	1/50 (2%)	6/50 (12%)	41/50 (82%)

Most frequent serious events

Showing 10 of 45

Most frequent serious events
Event	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (From Week 24)	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 2/Arm F: Placebo	Cohort 2 / Arm F1 (Period 2): CFZ533 300mg	Cohort 2/Arm E: CFZ533 600 mg
CholecystitisHepatobiliary disorders	0/43	1/41	0/44	0/42	0/44	0/50	0/44	0/50
TuberculosisInfections and infestations	0/43	1/41	0/44	0/42	0/44	0/50	0/44	0/50
OsteoarthritisMusculoskeletal and connective tissue disorders	0/43	1/41	0/44	0/42	0/44	0/50	0/44	0/50
NephrolithiasisRenal and urinary disorders	0/43	1/41	0/44	0/42	0/44	0/50	0/44	0/50
EnteritisGastrointestinal disorders	0/43	0/41	0/44	1/42	0/44	0/50	0/44	0/50
HaematocheziaGastrointestinal disorders	0/43	0/41	0/44	1/42	0/44	0/50	0/44	0/50
Pancreatitis acuteGastrointestinal disorders	0/43	0/41	0/44	1/42	0/44	0/50	0/44	0/50
COVID-19Infections and infestations	0/43	0/41	1/44	1/42	0/44	0/50	0/44	1/50
Pneumocystis jirovecii pneumoniaInfections and infestations	0/43	0/41	0/44	1/42	0/44	0/50	0/44	0/50
PneumoniaInfections and infestations	0/43	0/41	0/44	1/42	0/44	0/50	1/44	1/50

Most frequent other events

Showing 10 of 41

Most frequent other events
Event	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1 / Arm D1 (Period 2): CFZ533 600mg (From Week 24)	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 2/Arm F: Placebo	Cohort 2 / Arm F1 (Period 2): CFZ533 300mg	Cohort 2/Arm E: CFZ533 600 mg
COVID-19Infections and infestations	2/43	10/41	10/44	11/42	11/44	8/50	8/44	20/50
NasopharyngitisInfections and infestations	2/43	6/41	5/44	8/42	9/44	3/50	3/44	6/50
HeadacheNervous system disorders	5/43	1/41	9/44	6/42	8/44	5/50	4/44	3/50
Urinary tract infectionInfections and infestations	2/43	3/41	3/44	4/42	5/44	0/50	4/44	8/50
PyrexiaGeneral disorders	3/43	2/41	6/44	4/42	0/44	0/50	2/44	4/50
ArthralgiaMusculoskeletal and connective tissue disorders	4/43	2/41	6/44	2/42	5/44	4/50	5/44	5/50
Back painMusculoskeletal and connective tissue disorders	1/43	2/41	4/44	3/42	1/44	3/50	6/44	6/50
Upper respiratory tract infectionInfections and infestations	1/43	4/41	3/44	3/42	1/44	1/50	3/44	6/50
RashSkin and subcutaneous tissue disorders	0/43	2/41	1/44	2/42	1/44	4/50	0/44	6/50
NeutropeniaBlood and lymphatic system disorders	0/43	0/41	0/44	5/42	2/44	0/50	0/44	1/50

Baseline characteristics

Demographics and Baseline Characteristics were assessed in Period 1.

Age, Continuous
Age, Continuous(Years)	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg	Total
Mean	53.3 ± 9.55	49.3 ± 14.41	48.7 ± 12.78	52.6 ± 12.31	49.4 ± 13.40	53.6 ± 13.18	51.2 ± 12.61

Sex: Female, Male
Sex: Female, Male(Participants)	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg	Total
Female	41	42	41	40	48	50	262
Male	2	2	2	3	2	0	11

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Cohort 1 / Arm D (Period 1): Placebo	Cohort 1/Arm C: CFZ533 150 mg	Cohort 1/Arm B: CFZ533 300 mg	Cohort 1/Arm A: CFZ533 600 mg	Cohort 2/Arm F: Placebo	Cohort 2/Arm E: CFZ533 600 mg	Total
American Indian or Alaska Native	0	1	1	1	0	1	4
Asian	3	4	4	5	7	8	31
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	1	1	2	1	3	3	11
White	38	37	35	35	38	37	220
More than one race	1	1	1	1	1	0	5
Unknown or Not Reported	0	0	0	0	1	1	2

Study locations

71 sites

North GA Rheumatology Group PC
Suwanee, Georgia 30024, United States
Indiana Univ School of Dentistry
Indianapolis, Indiana 46202, United States
Ochsner Health System
Baton Rouge, Louisiana 70809, United States
The John Hopkins Jerome L Greene Sjogren
Baltimore, Maryland 21224, United States
Tufts School of Dental Medicine
Boston, Massachusetts 02111, United States
Winthrop University Hospital
Mineola, New York 11501, United States
Perelman School of Medicine
Philadelphia, Pennsylvania 19104, United States
Uni Wisconsin School Med Pub Health
Madison, Wisconsin 53792, United States
Novartis Investigative Site
Buenos Aires, C1055AAF, Argentina
Novartis Investigative Site
CABA, 1426, Argentina
Novartis Investigative Site
Nedlands, Western Australia 6009, Australia
Novartis Investigative Site
Graz, 8036, Austria
Novartis Investigative Site
Vienna, 1090, Austria
Novartis Investigative Site
Vitória, Espírito Santo 29055 450, Brazil
Novartis Investigative Site
Juiz de Fora, Minas Gerais 36010 570, Brazil
Novartis Investigative Site
São Paulo, São Paulo 01244-030, Brazil
Novartis Investigative Site
Toronto, Ontario M5T 2S8, Canada
Novartis Investigative Site
Rimouski, Quebec G5L 5T1, Canada
Novartis Investigative Site
Trois-Rivières, Quebec G9A 3Y2, Canada
Novartis Investigative Site
Valdivia, Los Ríos Region 5110683, Chile
Novartis Investigative Site
Santiago, RM 7500588, Chile
Novartis Investigative Site
Santiago, Santiago Metropolitan 7500571, Chile
Novartis Investigative Site
Santiago, Santiago Metropolitan 7500710, Chile
Novartis Investigative Site
Concepción, 6740, Chile
Novartis Investigative Site
Medellín, Antioquia 050001, Colombia
Novartis Investigative Site
Barranquilla, Atlántico 080002, Colombia
Novartis Investigative Site
Cali, Valle del Cauca Department 760012, Colombia
Novartis Investigative Site
Brest, 29200, France
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275, France
Novartis Investigative Site
Lille, 59037, France
Novartis Investigative Site
Paris, 75014, France
Novartis Investigative Site
Strasbourg, 67000, France
Novartis Investigative Site
Freiburg im Breisgau, Baden-Wurttemberg 79106, Germany
Novartis Investigative Site
Würzburg, Bavaria 97080, Germany
Novartis Investigative Site
Dresden, Saxony 01307, Germany
Novartis Investigative Site
Bonn, 53105, Germany
Novartis Investigative Site
Athens, 115 27, Greece
Novartis Investigative Site
Székesfehérvár, Fejér 8000, Hungary
Novartis Investigative Site
Budapest, 1023, Hungary
Novartis Investigative Site
Szeged, 6720, Hungary
Novartis Investigative Site
Haifa, 3104802, Israel
Novartis Investigative Site
Kfar Saba, 4428164, Israel
Novartis Investigative Site
Ramat Gan, 5265601, Israel
Novartis Investigative Site
Milan, MI 20132, Italy
Novartis Investigative Site
Pisa, PI 56126, Italy
Novartis Investigative Site
Udine, UD 33100, Italy
Novartis Investigative Site
Nagoya, Aichi-ken 457 8510, Japan
Novartis Investigative Site
Sasebo, Nagasaki 857-1195, Japan
Novartis Investigative Site
Kurashiki, Okayama-ken 710-0824, Japan
Novartis Investigative Site
Chuo Ku, Tokyo 104 8560, Japan
Novartis Investigative Site
Shinjuku-ku, Tokyo 160 8582, Japan
Novartis Investigative Site
Rotterdam, South Holland 3015 GD, Netherlands
Novartis Investigative Site
Groningen, 9713 GZ, Netherlands
Novartis Investigative Site
Almada, 2805-267, Portugal
Novartis Investigative Site
Lisbon, 1050-034, Portugal
Novartis Investigative Site
Lisbon, 1649-035, Portugal
Novartis Investigative Site
Ponte de Lima, 4990 041, Portugal
Novartis Investigative Site
Brasov, 500283, Romania
Novartis Investigative Site
Cluj-Napoca, 400006, Romania
Novartis Investigative Site
Kazan', 420097, Russia
Novartis Investigative Site
Moscow, 115522, Russia
Novartis Investigative Site
Orenburg, 460000, Russia
Novartis Investigative Site
Saint Petersburg, 195257, Russia
Novartis Investigative Site
Tomsk, 634009, Russia
Novartis Investigative Site
Yekaterinburg, 620028, Russia
Novartis Investigative Site
Seoul, Seocho Gu 06591, South Korea
Novartis Investigative Site
Stockholm, SE 113 65, Sweden
Novartis Investigative Site
Ankara, Yenimahalle 06500, Turkey (Türkiye)
Novartis Investigative Site
Birmingham, B15 2TH, United Kingdom
Novartis Investigative Site
Doncaster, DN2 5LT, United Kingdom
Novartis Investigative Site
Manchester, M13 9WL, United Kingdom

References and documents

Publications

Fisher BA, Mariette X, Papas A, Grader-Beck T, Bootsma H, Ng WF, van Daele PLA, Finzel S, Noaiseh G, Elgueta S, Hermann J, McCoy SS, Akpek E, Bookman A, Sopala M, Montecchi-Palmer M, Luo WL, Scheurer C, Hueber W; TWINSS study group. Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjogren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study. Lancet. 2024 Aug 10;404(10452):540-553. doi: 10.1016/S0140-6736(24)01211-X. Epub 2024 Jul 31. PubMed 39096929 ↗

Study documents

Study protocol · Apr 27, 2021
Statistical analysis plan · Jul 17, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 18, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03905525
Lead sponsor: Novartis Pharmaceuticals
Responsible party: Sponsor
First posted: Apr 5, 2019
Start date: Oct 1, 2019
Primary completion: Sep 28, 2022
Completion: Jun 6, 2023
Results posted: May 18, 2026
Last update: May 18, 2026

Study contacts

Study Director Novartis Pharmaceuticals

study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Sjogren's Syndrome→

Other studies from this sponsor

Novartis Pharmaceuticals

Start the discussion