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)
Overview
- Phase
- Phase 2
- Intervention
- CFZ533
- Conditions
- Sjögren Syndrome
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 273
- Locations
- 1
- Primary Endpoint
- Change in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score from baseline at 24 weeks as compared to placebo
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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.
Arms & Interventions
Cohort 1 /Arm A
CFZ533 dose 1
Intervention: CFZ533
Cohort 1/Arm B
CFZ533 dose 2
Intervention: CFZ533
Cohort 1/Arm C
CFZ533 dose 3
Intervention: CFZ533
Cohort 1/Arm D
Placebo dose (up to week 24)
Intervention: Placebo
Cohort 1/Arm D1
CFZ533 dose 1 (from week 24)
Intervention: CFZ533
Cohort 2/Arm E
CFZ533 dose 1
Intervention: CFZ533
Cohort 2/Arm F
Placebo dose (up to week 24)
Intervention: Placebo
Cohort 2/Arm F1
CFZ533 dose 2 (from week 24)
Intervention: CFZ533
Outcomes
Primary Outcomes
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
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
Secondary Outcomes
- Change from baseline in ESSPRI at Week 24(24 weeks)
- Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24(24 weeks)
- Percent change from baseline in plasma CXCL-13 levels at analysis visits up to end of study(60 weeks)
- Change from baseline in Physician Global Assessment (PhGA) at Week 24(24 weeks)
- Change from baseline in ESSDAI at Week 24(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.(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(60 weeks)
- Serum Free Light Chain (FLC) levels at analysis visit up to end of study(60 weeks)
- Immunoglobulin IgG and IgM levels at analysis visits up to end of study(60 weeks)