Safety, Pharmacokinetics and Preliminary Efficacy Study of CFZ533 in Patients With Primary Sjögren's Syndrome

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CFZ533 in Patients With Primary Sjögren's Syndrome

This study did evaluate the safety,tolerability and preliminary therapeutic efficacy of multiple doses of intravenous infusion of CFZ533 monoclonal antibody in patients with primary Sjögren's syndrome(pSS)

Study Overview

• Status: Completed
• Conditions: Primary Sjögren's Syndrome
• Intervention / Treatment: Drug: CFZ533 active - Cohort 2; Drug: CFZ533 placebo - Cohort 2; Drug: CFZ533 active - Cohort 1; Drug: CFZ533 placebo- Cohort 1; Drug: CFZ533 active -Cohort 3; Drug: CFZ533 active - Cohort 3

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Novartis Investigative Site
• Hungary
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, EC14 7BE
    • Novartis Investigative Site
  • Newcastle upon Tyne, United Kingdom, NE2 4HH
    • Novartis Investigative Site
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2WB
      • Novartis Investigative Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Novartis Investigative Site
  • New York
    • Mineola, New York, United States, 11501
      • Novartis Investigative Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of primary Sjögren's syndrome
• ESSDAI score ≥ 6

Exclusion Criteria:

• Secondary Sjögren's syndrome
• Receiving cyclosphosphamide, corticosteroid bolus with dose over 1 mg/kg, rituximab, belimunab, other immunosuppressives.
• At significant risk for thromboembolic event
• Clinically significant systemic infection
• Significant elevated risk for infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CFZ533 active- Cohort 2; multiple doses of CFZ533 intravenous infusion	Drug: CFZ533 active - Cohort 2; multiple doses of CFZ533 intravenous infusion
PLACEBO_COMPARATOR: CFZ533 placebo- Cohort 2; multiple doses of placebo intravenous infusion	Drug: CFZ533 placebo - Cohort 2; multiple doses of placebo intravenous infusion
EXPERIMENTAL: CFZ533 active - Cohort 1; multiple doses of CFZ533 s.c. injection	Drug: CFZ533 active - Cohort 1; multiple doses of CFZ533 s.c. injection
PLACEBO_COMPARATOR: CFZ533 placebo - Cohort 1; multiple doses of placebo s.c. injection	Drug: CFZ533 placebo- Cohort 1; multiple doses of placebo s.c. injection
EXPERIMENTAL: CFZ533 Treatment Arm 1 - Cohort 3; multiple doses of CFZ533 s.c. injection	Drug: CFZ533 active -Cohort 3; multiple doses of CFZ533 s.c. injection
EXPERIMENTAL: CFZ533 Treatment Arm 2 - Cohort 3; Single dose of CFZ533 i.v. infusion and multiple doses of CFZ533 s.c. injection	Drug: CFZ533 active - Cohort 3; Single dose of CFZ533 i.v. infusion and multiple doses of CFZ533 s.c. injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)	The effect of CFZ533 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123). A reduction from baseline indicates improvement in patients.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI)	The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms.	Baseline and Week 12
Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS)	The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).	Baseline and Week 12
Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS)	The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).	Baseline and Week 12
Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score	The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.	Baseline and Week 12
Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score	The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.	Baseline and Week 12
Change From Baseline in Multidimensional Fatigue Inventory (MFI)	The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a possible range from 4-20. The reported total score has a range from 20-100. A reduction from baseline in MFI indicates improvement.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicatrials.com

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 22, 2014
• Primary Completion (ACTUAL): June 29, 2018
• Study Completion (ACTUAL): June 29, 2018

Study Registration Dates

• First Submitted: November 4, 2014
• First Submitted That Met QC Criteria: November 11, 2014
• First Posted (ESTIMATE): November 14, 2014

Study Record Updates

• Last Update Posted (ACTUAL): January 5, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Sjögren's syndrome, CFZ533, ESSDAI
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: CCFZ533X2203