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

September 13, 2023 updated by: Novartis Pharmaceuticals

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 will evaluate safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple doses of CFZ533 (iscalimab) in patients with Sjögren's Syndrome.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a double-blind, randomized, placebo-controlled, multicenter study of CFZ533 in 2 distinct populations (cohorts) of patients with Sjögren's Syndrome: 1) moderate-to-severe disease (systemic and symptomatic involvement) and; 2) low systemic involvement but high symptom burden.

The study includes up to 6 weeks screening period, 48 weeks of treatment (divided into treatment periods of 24 weeks each) and 12 weeks follow up. Study treatment will be administered as bi-weekly subcutaneous injections.

Study Type

Interventional

Enrollment (Actual)

273

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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
      • Wien, Austria, 1090
        • Novartis Investigative Site
  • Brazil
    • ES
      • Vitoria, ES, Brazil, 29055 450
        • Novartis Investigative Site
    • MG
      • Juiz de Fora, MG, Brazil, 36010 570
        • Novartis Investigative Site
    • SP
      • São Paulo, SP, 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 Rivieres, Quebec, Canada, G8Z 1Y2
        • Novartis Investigative Site
  • Chile
      • Concepcion, Chile, 6740
        • Novartis Investigative Site
      • Santiago, Chile, 7500710
        • Novartis Investigative Site
      • Santiago, Chile, 7500571
        • Novartis Investigative Site
    • Los Rios
      • Valdivia, Los Rios, Chile, 5110683
        • Novartis Investigative Site
    • RM
      • Santiago, RM, Chile, 7500588
        • Novartis Investigative Site
  • Colombia
    • Antioquia
      • Medellin, Antioquia, Colombia, 050001
        • Novartis Investigative Site
    • Atlantico
      • Barranquilla, Atlantico, Colombia, 080002
        • Novartis Investigative Site
    • Valle Del Cauca
      • Cali, Valle Del Cauca, Colombia, 760012
        • Novartis Investigative Site
  • France
      • Brest, France, 29200
        • Novartis Investigative Site
      • Le Kremlin Bicetre, France, 94275
        • Novartis Investigative Site
      • Lille, France, 59000
        • Novartis Investigative Site
      • Paris, France, 75014
        • Novartis Investigative Site
      • Strasbourg, France, 67000
        • Novartis Investigative Site
  • Germany
      • Bonn, Germany, 53105
        • Novartis Investigative Site
      • Dresden, Germany, 01307
        • Novartis Investigative Site
      • Freiburg, Germany, 79106
        • Novartis Investigative Site
      • Wuerzburg, Germany, 97080
        • Novartis Investigative Site
  • Greece
      • Athens, Greece, 115 27
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1023
        • Novartis Investigative Site
      • Szeged, Hungary, 6720
        • Novartis Investigative Site
    • Fejer
      • Szekesfehervar, Fejer, Hungary, 8000
        • Novartis Investigative Site
  • Israel
      • Haifa, Israel, 3339419
        • Novartis Investigative Site
      • Kfar Saba, Israel, 44281
        • Novartis Investigative Site
      • Ramat Gan, Israel, 52621
        • Novartis Investigative Site
  • Italy
    • MI
      • Milano, MI, Italy, 20132
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italy, 56124
        • Novartis Investigative Site
    • UD
      • Udine, UD, Italy, 33100
        • Novartis Investigative Site
  • Japan
    • Aichi
      • Nagoya, Aichi, Japan, 457 8510
        • Novartis Investigative Site
    • Nagasaki
      • Sasebo-city, Nagasaki, Japan, 857-1165
        • Novartis Investigative Site
    • Okayama
      • Kurashiki, Okayama, Japan, 710-8522
        • Novartis Investigative Site
    • Tokyo
      • Chuo ku, Tokyo, Japan, 104-8560
        • Novartis Investigative Site
      • Shinjuku-ku, Tokyo, Japan, 160 8582
        • Novartis Investigative Site
  • Korea, Republic of
    • Seocho Gu
      • Seoul, Seocho Gu, Korea, Republic of, 06591
        • Novartis Investigative Site
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
      • Rotterdam, Netherlands, 3015 CE
        • Novartis Investigative Site
  • Portugal
      • Almada, Portugal, 2801 951
        • Novartis Investigative Site
      • Lisboa, Portugal, 1050-034
        • Novartis Investigative Site
      • Lisboa, 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
  • Russian Federation
      • Ekaterinburg, Russian Federation, 620028
        • Novartis Investigative Site
      • Kazan, Russian Federation, 420097
        • Novartis Investigative Site
      • Moscow, Russian Federation, 115522
        • Novartis Investigative Site
      • Orenburg, Russian Federation, 460000
        • Novartis Investigative Site
      • St Petersburg, Russian Federation, 195257
        • Novartis Investigative Site
      • Tomsk, Russian Federation, 634009
        • Novartis Investigative Site
  • Sweden
    • SE
      • Stockholm, SE, Sweden, 113 65
        • Novartis Investigative Site
  • Turkey
      • Ankara, Turkey, 06560
        • 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
      • Duluth, Georgia, United States, 30096
        • Novartis Investigative Site
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Novartis Investigative Site
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Novartis Investigative Site
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Novartis Investigative Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Novartis Investigative Site
    • New York
      • Mineola, New York, United States, 11501
        • Novartis Investigative Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Novartis Investigative Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed informed consent
  • Male or female patient ≥ 18 years of age
  • Classification of Sjögren's Syndrome according to ACR/EULAR 2016 criteria (Shiboski et al 2017)
  • Seropositive for anti-Ro/SSA antibodies
  • Stimulated whole salivary flow rate of ≥ 0.1 mL/min

Inclusion criteria specific for Cohort 1:

  • ESSDAI ≥ 5 within the 8 predefined organ domains
  • ESSPRI score of ≥5

Inclusion criteria specific for Cohort 2:

  • ESSDAI < 5 within 8 domains scored for inclusion criterion for Cohort 1
  • ESSPRI fatigue subscore ≥ 5 or ESSPRI dryness subscore ≥ 5

Exclusion Criteria:

  • Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness
  • Use of other investigational drugs
  • Prior use of B cell depleting therapies, abatacept or any other immunosuppressants unless specifically allowed be the protocol.
  • Use of steroids at dose >10 mg/day.
  • Uncontrolled ocular rosacea (affecting the eye adnexa), posterior blepharitis or Meibomian gland disease (this criterion applies only to patients considered for Cohort 2)
  • Active viral, bacterial or other infections requiring systemic treatment
  • Receipt of live/attenuated vaccine within a 2-month period prior to randomization.
  • Chronic infection with hepatitis B (HBV) or hepatitis C (HCV).
  • Evidence of active tuberculosis (TB) infection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 /Arm A
CFZ533 dose 1
Drug: CFZ533
Biological
Other Names:
  • iscalimab
Experimental: Cohort 1/Arm B
CFZ533 dose 2
Drug: CFZ533
Biological
Other Names:
  • iscalimab
Experimental: Cohort 1/Arm C
CFZ533 dose 3
Drug: CFZ533
Biological
Other Names:
  • iscalimab
Placebo Comparator: Cohort 1/Arm D
Placebo dose (up to week 24)
Other: Placebo
liquid placebo for injections
Experimental: Cohort 1/Arm D1
CFZ533 dose 1 (from week 24)
Drug: CFZ533
Biological
Other Names:
  • iscalimab
Experimental: Cohort 2/Arm E
CFZ533 dose 1
Drug: CFZ533
Biological
Other Names:
  • iscalimab
Placebo Comparator: Cohort 2/Arm F
Placebo dose (up to week 24)
Other: Placebo
liquid placebo for injections
Experimental: Cohort 2/Arm F1
CFZ533 dose 2 (from week 24)
Drug: CFZ533
Biological
Other Names:
  • iscalimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo
Time Frame: 24 weeks
Cohort 1 - Efficacy
24 weeks
Change in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score from baseline at 24 weeks as compared to placebo.
Time Frame: 24 weeks
Cohort 2 - Efficacy
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in ESSPRI at Week 24
Time Frame: 24 weeks
Cohort 1 - Efficacy (Patient Reported Outcomes)
24 weeks
Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24
Time Frame: 24 weeks
Cohort 1&2 - Efficacy (Patient Reported Outcomes)
24 weeks
Change from baseline in Physician Global Assessment (PhGA) at Week 24
Time Frame: 24 weeks
Cohort 1&2 - Efficacy (Clinical Outcome Measures)
24 weeks
Change from baseline in ESSDAI at Week 24
Time Frame: 24 weeks
Cohort 2 - Efficacy (Clinical Outcome Measures)
24 weeks
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.
Time Frame: 24 weeks
Cohort 2 - Efficacy (Patient Reported Outcomes)
24 weeks
Incidence of adverse events (AEs), serious adverse events (SAEs) from baseline to Week 24 and from week 24 to the end of study
Time Frame: 60 weeks
Cohort 1&2 - Safety
60 weeks
Serum Free Light Chain (FLC) levels at analysis visit up to end of study
Time Frame: 60 weeks
Cohort 1&2 - Biomarkers (1)
60 weeks
Immunoglobulin IgG and IgM levels at analysis visits up to end of study
Time Frame: 60 weeks
Cohort 1&2 - Biomarkers (2)
60 weeks
Percent change from baseline in plasma CXCL-13 levels at analysis visits up to end of study
Time Frame: 60 weeks

Cohort 1&2 - Biomarkers (3)

Chemokine (C-X-C motif) ligand 13 (CXCL13), also known as B lymphocyte chemoattractant (BLC) or B cell-attracting chemokine 1 (BCA-1), is a protein ligand that in humans is encoded by the CXCL13 gene.
60 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Study Director Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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)

September 15, 2023

Last Update Submitted That Met QC Criteria

September 13, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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