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

Phase 2

Completed

• Conditions: Sjögren Syndrome
• Interventions: Drug: CFZ533; Other: Placebo

• Registration Number: NCT03905525
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

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 Timeline

• Study First Submitted: 2019-03-25
• Study First Submitted QC: 2019-04-04
• Study First Posted: 2019-04-05
• Study Start: 2019-10-01
• Primary Completion: 2022-09-28
• Disposition First Submitted: 2022-10-04
• Disposition First Submitted QC: 2022-10-12
• Disposition First Posted: 2022-10-17
• Study Completion: 2023-06-06
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-13
• Last Update Posted: 2023-09-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 273

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 /Arm A	CFZ533	CFZ533 dose 1
Cohort 1/Arm B	CFZ533	CFZ533 dose 2
Cohort 1/Arm C	CFZ533	CFZ533 dose 3
Cohort 1/Arm D	Placebo	Placebo dose (up to week 24)
Cohort 1/Arm D1	CFZ533	CFZ533 dose 1 (from week 24)
Cohort 2/Arm E	CFZ533	CFZ533 dose 1
Cohort 2/Arm F	Placebo	Placebo dose (up to week 24)
Cohort 2/Arm F1	CFZ533	CFZ533 dose 2 (from week 24)

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Manchester, United Kingdom