Sjögren Syndrome
Conditions
Keywords
Sjögren, fatigue, dryness, anti-CD40, CFZ533, iscalimab, TWINSS, autoimmune
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.
Interventions
DRUGCFZ533
Biological
OTHERPlacebo
liquid placebo for injections
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients, investigator staff, persons performing the assessments, will remain blind to the identity of the treatment within each cohort from the time of randomization until end of the study visit (week 60)
Intervention model description
Patients will be screened and enrolled into one of the 2 study Cohorts: Cohort 1: At baseline subjects will be randomized in ratio 1:1:1:1 into one of three CFZ533 (iscalimab) arms (A, B or C) or to placebo (Arm D). After completion of 24 weeks of treatment (Period 1) placebo patients (Arm D) will be switched to active treatment (Arm D1) for the subsequent 24 weeks (Period 2). Cohort 2: At baseline subjects will be randomized in ratio 1:1 to iscalimab (Arm E) or to placebo (Arm F). After completion of 24 weeks of treatment (Period 1), placebo patients (Arm F) will be switched to iscalimab active treatment (Arm F1) for the subsequent 24 weeks (Period 2). All patients treated with iscalimab (Arms A,B,C,and E) in Period 1 will continue the same study treatment in Period 2.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Change from baseline in ESSPRI at Week 24 | 24 weeks | Cohort 1 - Efficacy (Patient Reported Outcomes) |
| 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) |
| 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. |
| 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 |
| 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) |
Countries
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, United States
Outcome results
None listed