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

NCT ID: NCT04541589

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 206 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-05
• Study Completion Date: 2024-08-19

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.

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).

Conditions

Sjogren's Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Iscalimab

Intervention Type: 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).

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.

Group Type: EXPERIMENTAL

Iscalimab

Intervention Type: 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).

Placebo

Intervention Type: 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

Interventions

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).

Intervention Type: DRUG

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

Intervention Type: OTHER

Other Intervention Names

CFZ533

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

North GA Rheumatology Group PC

Suwanee, Georgia, United States

Ochsner Health System

Baton Rouge, Louisiana, United States

The John Hopkins Jerome L Greene Sjogren

Baltimore, Maryland, United States

Tufts School of Dental Medicine

Boston, Massachusetts, United States

Winthrop University Hospital

Mineola, New York, United States

Perelman School of Medicine

Philadelphia, Pennsylvania, United States

Uni Wisconsin School Med Pub Health

Madison, Wisconsin, United States

Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, Argentina

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CABA, , Argentina

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Nedlands, Western Australia, Australia

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Graz, , Austria

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Vienna, , Austria

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Vitória, Espírito Santo, Brazil

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Juiz de Fora, Minas Gerais, Brazil

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São Paulo, São Paulo, Brazil

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Toronto, Ontario, Canada

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Rimouski, Quebec, Canada

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Trois-Rivières, Quebec, Canada

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Valdivia, Los Ríos Region, Chile

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Santiago, RM, Chile

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Santiago, , Chile

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Santiago, , Chile

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Medellín, Antioquia, Colombia

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Barranquilla, Atlántico, Colombia

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Brest, , France

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Le Kremlin-Bicêtre, , France

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Lille, , France

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Strasbourg, , France

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Bonn, , Germany

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Dresden, , Germany

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Freiburg im Breisgau, , Germany

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Würzburg, , Germany

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Athens, , Greece

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Székesfehérvár, Fejér, Hungary

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Szeged, , Hungary

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Haifa, , Israel

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Kfar Saba, , Israel

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Ramat Gan, , Israel

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Milan, MI, Italy

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Pisa, PI, Italy

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Nagoya, Aichi-ken, Japan

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Sasebo, Nagasaki, Japan

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Kurashiki, Okayama-ken, Japan

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Chuo Ku, Tokyo, Japan

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Rotterdam, South Holland, Netherlands

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Groningen, , Netherlands

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Lisbon, , Portugal

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Lisbon, , Portugal

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Ponte de Lima, , Portugal

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Brasov, , Romania

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Cluj-Napoca, , Romania

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Kazan', , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Tomsk, , Russia

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Yekaterinburg, , Russia

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Seoul, Seocho Gu, South Korea

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Stockholm, SE, Sweden

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Ankara, , Turkey (Türkiye)

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Birmingham, , United Kingdom

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Doncaster, , United Kingdom

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Manchester, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Brazil; Canada; Chile; Colombia; France; Germany; Greece; Hungary; Israel; Italy; Japan; Netherlands; Portugal; Romania; Russia; South Korea; Sweden; Turkey (Türkiye); United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.gov/ct2/show/NCT03905525?term=CCFZ533B2201&draw=2&rank=1

Core study

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2657

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

Other Identifiers

2020-001942-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CCFZ533B2201E1

Identifier Type: -

Identifier Source: org_study_id