Study of Safety and Tolerability of CFZ533 in Patients With Sjögren's Syndrome (TWINSS Extn)

A TWINSS Extension Trial to Evaluate the Safety and Tolerability of CFZ533 (Iscalimab) at Two Dose Levels Administered Subcutaneously in Patients With Sjögren's Syndrome

This study will evaluate the safety and tolerability of iscalimab at two dose levels in patients with Sjögren's Syndrome, who participated in the TWINSS core study, CCFZ533B2201 (NCT03905525). Additionally, this Extension study will further explore the pharmacokinetics (PK) and efficacy of iscalimab at two dose level.

Study Overview

• Status: Completed
• Conditions: Sjogren's Syndrome
• Intervention / Treatment: Drug: Iscalimab; Other: Placebo

Detailed Description

This study was a continuation of the TWINSS core study CCFZ533B2201 (NCT03905525) that offered continuation of treatment for participants who completed the core study 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. The extension study was a 48-week treatment study, with a safety follow-up period of 12 weeks, to provide additional safety and tolerability information for iscalimab.At Week 60 of the TWINSS core study, eligible participants had the option to enroll in the extension study.

Participants were classified as treatment responders or non-responder based on their European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI) and EULAR Sjögren's syndrome patient reported index (ESSPRI) scores from predefined time points in the core study. In the extension study, participants were reassigned to either iscalimab 600 mg or 300 mg subcutaneously via prefilled syringes (PFS) based on their responder status and the iscalimab doses that they received in the core study

All participants enrolled in the extension study received a weekly loading regimen at the start of the treatment period for the initial 3 weeks, followed by a subcutaneous maintenance regimen (600 or 300 mg subcutaneously every 2 weeks). Injections were performed at site or at home by site staff or participant/caregiver.

Study blinding for the extension study was maintained until final database lock of the core study, upon which the participants and Investigators were unblinded, making it an open-label study through Week 120 (end of study visit).

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, 1426
    • Novartis Investigative Site
  • Buenos Aires
    • Ciudad Autonoma de Bs As, Buenos Aires, Argentina, C1055AAF
      • 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
  • Santiago, Chile, 7500710
    • Novartis Investigative Site
  • Santiago, Chile, 7500571
    • Novartis Investigative Site
  • Los Ríos Region
    • Valdivia, Los Ríos Region, Chile, 5110683
      • Novartis Investigative Site
  • RM
    • Santiago, RM, Chile, 7500588
      • Novartis Investigative Site
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050001
      • Novartis Investigative Site
  • Atlántico
    • Barranquilla, Atlántico, Colombia, 080002
      • Novartis Investigative Site
• France
  • Brest, France, 29200
    • Novartis Investigative Site
  • Le Kremlin-Bicêtre, France, 94275
    • Novartis Investigative Site
  • Lille, France, 59037
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
• Germany
  • Bonn, Germany, 53105
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Freiburg im Breisgau, Germany, 79106
    • Novartis Investigative Site
  • Würzburg, Germany, 97080
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 115 27
    • Novartis Investigative Site
• Hungary
  • 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, 56124
      • 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
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015 GD
      • Novartis Investigative Site
• Portugal
  • Lisbon, Portugal, 1050-034
    • Novartis Investigative Site
  • Lisbon, Portugal, 1649 035
    • 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
  • 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)
  • Ankara, 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
  • 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 to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants had to have participated in the TWINSS core study, CCFZ533B2201 (NCT03905525), and had to have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60.
2. Signed informed consent had to be obtained prior to participation in the Extension study (i.e., before commencement of the Week 60 assessments of the core study).
3. In the judgment of the Investigator, participants had to be expected to clinically benefit from continued iscalimab therapy.

Exclusion Criteria:

1. Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constituted the principle illness, specifically:

   • Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA positivity and renal involvement, or other organ involvement that impeded on the ability to score ESSDAI domains
   • Active rheumatoid arthritis (RA) that impeded on the ability to score the ESSDAI articular domain
   • Systemic sclerosis
   • Any other concurrent connective tissue disease (e.g., lupus nephritis (LN), large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease) that was active and required immunosuppressive treatment outside the scope of this trial and would impede on Sjögren's Syndrome organ domain assessments
2. Use of other investigational drugs other than iscalimab during the core study
3. Active uncontrolled viral, bacterial or other infections requiring systemic treatment at the time of enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms
4. Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test
5. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they were using highly effective methods of contraception during dosing and for 14 weeks after stopping the investigational drug.
6. Missing ESSDAI (Cohort 1 and Cohort 2) or ESSPRI (Cohort 2) scores in the core study at Weeks 0 and 4 or Weeks 40 and 48.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Iscalimab; Iscalimab 600 mg or 300 mg was administered subcutaneously weekly for the first 3 weeks. Subsequently, iscalimab was administered subcutaneously bi-weekly (every other week or Q2W).; Other Names: CFZ533
Experimental: 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.	Drug: Iscalimab; Iscalimab 600 mg or 300 mg was administered subcutaneously weekly for the first 3 weeks. Subsequently, iscalimab was administered subcutaneously bi-weekly (every other week or Q2W).; Other Names: CFZ533; Other: Placebo; Placebo (1 injection of 2 ml) administered to participants in the iscalimab 300 mg arm to maintain blinding until the final database lock of the core study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Free Iscalimab Concentration in Plasma	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).	Predose at Day 1, 113, 225, 337 and 421
Incidence of Anti-iscalimab Antibodies in Plasma	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).	60 weeks

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Core study
• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Actual): August 19, 2024
• Study Completion (Actual): August 19, 2024

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Sjogren's Syndrome; autoimmune; anti-CD40; ESSDAI; ESSPRI; CFZ533; iscalimab; TWINSS Extension
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Skin and Connective Tissue Diseases; Sjogren's Syndrome; Physiological Effects of Drugs; Immunologic Factors; iscalimab
• Other Study ID Numbers: CCFZ533B2201E1; 2020-001942-20 (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