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

Sjögren Syndrome Clinical Trial

— TWINSS  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03905525
• Other study ID #: CCFZ533B2201
• Secondary ID: 2018-004476-35
• Status: Completed
• Phase: Phase 2
• Start date: October 1, 2019
• Est. completion date: June 6, 2023

Study information

• Verified date: September 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 273
• Est. completion date: June 6, 2023
• Est. primary completion date: September 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sjögren Syndrome
• Sjogren's Syndrome
• Syndrome

Intervention

Drug:
• CFZ533
Biological

Other:
• Placebo
liquid placebo for injections

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Australia	Novartis Investigative Site	Nedlands	Western Australia
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Wien
Brazil	Novartis Investigative Site	Juiz de Fora	MG
Brazil	Novartis Investigative Site	São Paulo	SP
Brazil	Novartis Investigative Site	Vitoria	ES
Canada	Novartis Investigative Site	Rimouski	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Trois Rivieres	Quebec
Chile	Novartis Investigative Site	Concepcion
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago	RM
Chile	Novartis Investigative Site	Valdivia	Los Rios
Colombia	Novartis Investigative Site	Barranquilla	Atlantico
Colombia	Novartis Investigative Site	Cali	Valle Del Cauca
Colombia	Novartis Investigative Site	Medellin	Antioquia
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Wuerzburg
Greece	Novartis Investigative Site	Athens
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szekesfehervar	Fejer
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Udine	UD
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Kurashiki	Okayama
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Sasebo-city	Nagasaki
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Portugal	Novartis Investigative Site	Almada
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Ponte de Lima
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Cluj Napoca
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Orenburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Tomsk
Sweden	Novartis Investigative Site	Stockholm	SE
Turkey	Novartis Investigative Site	Ankara
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Doncaster
United Kingdom	Novartis Investigative Site	Manchester
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Baton Rouge	Louisiana
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Duluth	Georgia
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Mineola	New York
United States	Novartis Investigative Site	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  Colombia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Portugal,  Romania,  Russian Federation,  Sweden,  Turkey,  United Kingdom, 

Outcome

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