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

A 48-week, 6-arm, Randomized, Double-blind, Placebo-controlled Multicenter Trial to Assess the Safety and Efficacy of Multiple CFZ533 Doses Administered Subcutaneously in Two Distinct Populations of Patients With Sjogren's Syndrome (TWINSS)

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).

Study Overview

• Status: Completed
• Conditions: Sjögren Syndrome
• Intervention / Treatment: Drug: CFZ533; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 273
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Both cohorts must have met all the following criteria:

1. Signed informed consent must be obtained prior to participation in the study
2. Male or female patient >= 18 years of age
3. Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2016)
4. Seropositive for anti-Ro/SSA antibodies
5. Stimulated whole salivary flow rate of >= 0.1 mL/min

6. Able to communicate well with the Investigator to understand and comply with the requirements of the study

   Inclusion criteria specific for Cohort 1:

7. 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

8. Screening ESSPRI score of >= 5

   Inclusion criteria specific for Cohort 2:

9. Screening ESSDAI value < 5 within 8 domains scored for inclusion criterion #7 Cohort 1
10. Screening ESSPRI fatigue subscore >= 5 or ESSPRI dryness subscore >= 5
11. 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)
12. Score of >= 30 on IDEEL symptom bother questionnaire at Screening

Exclusion Criteria:

1. Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principal illness
2. 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

3. 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
4. Use of steroids (predniso(lo)ne or equivalent corticosteroid) at dose > 10 mg/day
5. Use of steroids and synthetic DMARDS at inconsistent dose and within 3 months prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; Biological; Other Names: iscalimab
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; Biological; Other Names: iscalimab
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; Biological; Other Names: iscalimab
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; liquid placebo for injections
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; Biological; Other Names: iscalimab
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; Biological; Other Names: iscalimab
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; liquid placebo for injections
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; Biological; Other Names: iscalimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Baseline, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Baseline, Week 4, Week 12, Week 24 (End Treatment Period 1), Week 32, Week 48 (End Treatment Period 2), FUP 3 (Week 60)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Study Director Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): September 28, 2022
• Study Completion (Actual): June 6, 2023

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: fatigue; monoclonal antibody; autoimmune disease; anti-CD40; dryness; TWINSS; sicca syndrome; European League Against Rheumatism (EULAR); Sjögren Syndrome (SjS); EULAR Sjögren syndrome disease activity index (ESSDAI); EULAR Sjögren syndrome patient reported index (ESSPRI); iscalimab (CFZ533)
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Immune System Diseases; Eye Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Fatigue; Sjogren's Syndrome; Autoimmune Diseases; iscalimab
• Other Study ID Numbers: CCFZ533B2201; 2018-004476-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No