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

NCT04541589 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CCFZ533B2201E12020-001942-20
• Study Type: interventional
• Target: 206
• Locations: 22 countries
• Sites: 61

Brief Summary

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.

Conditions

Sjogren's Syndrome

Keywords

Sjogren's Syndrome; autoimmune; ESSDAI; ESSPRI; anti-CD40; CFZ533; iscalimab; TWINSS Extension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Free Iscalimab Concentration in Plasma

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

• Incidence of Anti-iscalimab Antibodies in Plasma

  60 weeks

Study Arms (2)

Arm 1: Iscalimab 600 mg

EXPERIMENTAL

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

Arm 2 - Iscalimab 300 mg

EXPERIMENTAL

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; Other: Placebo

Interventions

Iscalimab DRUG

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).

Also known as: CFZ533

Arm 1: Iscalimab 600 mg; Arm 2 - Iscalimab 300 mg

Placebo OTHER

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

Arm 2 - Iscalimab 300 mg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• In the judgment of the Investigator, participants had to be expected to clinically benefit from continued iscalimab therapy.

You may not qualify if:

• 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
• Use of other investigational drugs other than iscalimab during the core study
• 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
• 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
• 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.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (62)

North GA Rheumatology Group PC

Suwanee, Georgia, 30024, United States

Location

Ochsner Health System

Baton Rouge, Louisiana, 70809, United States

Location

The John Hopkins Jerome L Greene Sjogren

Baltimore, Maryland, 21224, United States

Location

Tufts School of Dental Medicine

Boston, Massachusetts, 02111, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Uni Wisconsin School Med Pub Health

Madison, Wisconsin, 53792, United States

Location

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1055AAF, Argentina

Location

Novartis Investigative Site

CABA, 1426, Argentina

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Graz, 8036, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Vitória, Espírito Santo, 29055 450, Brazil

Location

Novartis Investigative Site

Juiz de Fora, Minas Gerais, 36010 570, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01244-030, Brazil

Location

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Toronto, Ontario, M5T 2S8, Canada

Location

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Rimouski, Quebec, G5L 5T1, Canada

Location

Novartis Investigative Site

Trois-Rivières, Quebec, G9A 3Y2, Canada

Location

Novartis Investigative Site

Valdivia, Los Ríos Region, 5110683, Chile

Location

Novartis Investigative Site

Santiago, RM, 7500588, Chile

Location

Novartis Investigative Site

Santiago, 7500571, Chile

Location

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Santiago, 7500710, Chile

Location

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Medellín, Antioquia, 050001, Colombia

Location

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Barranquilla, Atlántico, 080002, Colombia

Location

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Brest, 29200, France

Location

Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

Location

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Lille, 59037, France

Location

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Strasbourg, 67000, France

Location

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Bonn, 53105, Germany

Location

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Dresden, 01307, Germany

Location

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Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

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Athens, 115 27, Greece

Location

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Székesfehérvár, Fejér, 8000, Hungary

Location

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Szeged, 6720, Hungary

Location

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Haifa, 3104802, Israel

Location

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Kfar Saba, 4428164, Israel

Location

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Ramat Gan, 5265601, Israel

Location

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Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 457 8510, Japan

Location

Novartis Investigative Site

Sasebo, Nagasaki, 857-1195, Japan

Location

Novartis Investigative Site

Kurashiki, Okayama-ken, 710-0824, Japan

Location

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Chuo Ku, Tokyo, 104 8560, Japan

Location

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Rotterdam, South Holland, 3015 GD, Netherlands

Location

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Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Lisbon, 1050-034, Portugal

Location

Novartis Investigative Site

Lisbon, 1649 035, Portugal

Location

Novartis Investigative Site

Ponte de Lima, 4990 041, Portugal

Location

Novartis Investigative Site

Brasov, 500283, Romania

Location

Novartis Investigative Site

Cluj-Napoca, 400006, Romania

Location

Novartis Investigative Site

Kazan', 420097, Russia

Location

Novartis Investigative Site

Moscow, 115522, Russia

Location

Novartis Investigative Site

Saint Petersburg, 195257, Russia

Location

Novartis Investigative Site

Tomsk, 634009, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620028, Russia

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Stockholm, SE, 113 65, Sweden

Location

Novartis Investigative Site

Ankara, 06500, Turkey (Türkiye)

Location

Novartis Investigative Site

Birmingham, B15 2TH, United Kingdom

Location

Novartis Investigative Site

Doncaster, DN2 5LT, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Sjogren's Syndrome

Interventions

iscalimab

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study was conducted as a double-blind treatment until the final database lock of the Core study (NCT03905525). During this period, participants, Investigator, site staff, and persons performing the assessments remained blinded to the identity of the treatment until the final database lock of Core study (NCT03905525)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: September 9, 2020
• Study Start: January 5, 2021
• Primary Completion: August 19, 2024
• Study Completion: August 19, 2024
• Last Updated: October 16, 2025
• Results First Posted: June 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

RU (5); AU (2); SE (1); HU (2); FR (4); TU (1); BR (3); DE (4); IT (2); CL (4); GR (1); PT (3); RO (2); GB (3); CA (3); AR (2); KR (1); US (7); CO (2); IL (3); JP (4); NL (2)