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

• ClinicalTrials.gov Identifier: NCT02291029
• Recruitment Status: Completed
• First Posted: November 14, 2014
• Results First Posted: August 14, 2019
• Last Update Posted: January 5, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Primary Sjögren's Syndrome	Drug: CFZ533 active - Cohort 1; Drug: CFZ533 placebo- Cohort 1; Drug: CFZ533 active - Cohort 2; Drug: CFZ533 placebo - Cohort 2; Drug: CFZ533 active -Cohort 3; Drug: CFZ533 active - Cohort 3	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 22, 2014
• Actual Primary Completion Date: June 29, 2018
• Actual Study Completion Date: June 29, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) [ Time Frame: Baseline and Week 12 ]

   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.

Secondary Outcome Measures :

1. Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) [ Time Frame: Baseline and Week 12 ]
   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.
2. Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) [ Time Frame: Baseline and Week 12 ]
   The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).
3. Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) [ Time Frame: Baseline and Week 12 ]
   The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).
4. Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score [ Time Frame: Baseline and Week 12 ]
   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.
5. Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score [ Time Frame: Baseline and Week 12 ]
   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.
6. Change From Baseline in Multidimensional Fatigue Inventory (MFI) [ Time Frame: Baseline and Week 12 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Novartis Investigative Site

Boston, Massachusetts, United States, 02111

United States, New York

Novartis Investigative Site

Mineola, New York, United States, 11501

United States, Pennsylvania

Novartis Investigative Site

Duncansville, Pennsylvania, United States, 16635

Germany

Novartis Investigative Site

Berlin, Germany, 10117

Hungary

Novartis Investigative Site

Debrecen, Hungary, 4032

Switzerland

Novartis Investigative Site

Basel, Switzerland, 4031

United Kingdom

Novartis Investigative Site

Edgbaston, Birmingham, United Kingdom, B15 2WB

Novartis Investigative Site

London, United Kingdom, EC14 7BE

Novartis Investigative Site

Newcastle upon Tyne, United Kingdom, NE2 4HH

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] May 24, 2017

Statistical Analysis Plan  [PDF] September 5, 2018

More Information

Additional Information:

A Plain Language Trial Summary is available on novartisclinicatrials.com 

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02291029
• Other Study ID Numbers: CCFZ533X2203
• First Posted: November 14, 2014
• Results First Posted: August 14, 2019
• Last Update Posted: January 5, 2021
• Last Verified: July 2019

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Sjögren's syndrome, CFZ533, ESSDAI

Additional relevant MeSH terms:

Sjogren's Syndrome; Syndrome; Dry Eye Syndromes; Disease; Pathologic Processes; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs