Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjögren's Syndrome (TWINSS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03905525
Recruitment Status : Recruiting
First Posted : April 5, 2019
Last Update Posted : August 16, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( 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.

Condition or disease Intervention/treatment Phase
Sjögren Syndrome Drug: CFZ533 Other: Placebo Phase 2

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 screning period, 48 weeks of treatment (divided into treatment periods of 24 weeks each) and 12 weeks follow up. Study treament will be administered as bi-weekly subcutaneous injections.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, 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)
Primary Purpose: Treatment
Official Title: 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 Sjögren's Syndrome (TWINSS)
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : March 16, 2022
Estimated Study Completion Date : February 22, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 1 /Arm A
CFZ533 dose 1
Drug: CFZ533
Biological
Other Name: iscalimab

Experimental: Cohort 1/Arm B
CFZ533 dose 2
Drug: CFZ533
Biological
Other Name: iscalimab

Experimental: Cohort 1/Arm C
CFZ533 dose 3
Drug: CFZ533
Biological
Other Name: iscalimab

Placebo Comparator: Cohort 1/Arm D
Placebo dose (up to week 24)
Other: Placebo
liquid placebo for injections

Experimental: Cohort 1/Arm D1
CFZ533 dose 1 (from week 24)
Drug: CFZ533
Biological
Other Name: iscalimab

Experimental: Cohort 2/Arm E
CFZ533 dose 1
Drug: CFZ533
Biological
Other Name: iscalimab

Placebo Comparator: Cohort 2/Arm F
Placebo dose (up to week 24)
Other: Placebo
liquid placebo for injections

Experimental: Cphort 2/Arm F1
CFZ533 dose 2 (from week 24)
Drug: CFZ533
Biological
Other Name: iscalimab




Primary Outcome Measures :
  1. 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

  2. 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 Outcome Measures :
  1. Change from baseline in ESSPRI at Week 24 [ Time Frame: 24 weeks ]
    Cohort 1 - Efficacy (Patient Reported Outcomes)

  2. Change from baseline in score of Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire at Week 24 [ Time Frame: 24 weeks ]
    Cohort 1&2 - Efficacy (Patient Reported Outcomes)

  3. Change from baseline in Physician Global Assessment (PhGA) at Week 24 [ Time Frame: 24 weeks ]
    Cohort 1&2 - Efficacy (Clinical Outcome Measures)

  4. Change from baseline in ESSDAI at Week 24 [ Time Frame: 24 weeks ]
    Cohort 2 - Efficacy (Clinical Outcome Measures)

  5. 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. [ Time Frame: 24 weeks ]
    Cohort 2 - Efficacy (Patient Reported Outcomes)

  6. Incidence of adverse events (AEs), serious adverse events (SAEs) from baseline to Week 24 and from week 24 to the end of study [ Time Frame: 60 weeks ]
    Cohort 1&2 - Safety

  7. Serum Free Light Chain (FLC) levels at analysis visit up to end of study [ Time Frame: 60 weeks ]
    Cohort 1&2 - Biomarkers (1)

  8. Immunoglobulin IgG and IgM levels at analysis visits up to end of study [ Time Frame: 60 weeks ]
    Cohort 1&2 - Biomarkers (2)

  9. Percent change from baseline in plasma CXCL-13 levels at analysis visits up to end of study [ Time Frame: 60 weeks ]
    Cohort 1&2 - Biomarkers (3)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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 allowe 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905525


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
Show Show 80 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Study Director Novartis Pharmaceuticals Novartis Pharmaceuticals
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03905525    
Other Study ID Numbers: CCFZ533B2201
First Posted: April 5, 2019    Key Record Dates
Last Update Posted: August 16, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Sjögren
fatigue
dryness
anti-CD40
CFZ533
iscalimab
TWINSS
autoimmune
Additional relevant MeSH terms:
Layout table for MeSH terms
Sjogren's Syndrome
Syndrome
Disease
Pathologic Processes
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases