Study of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjögren's Syndrome (TWINSS)
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| ClinicalTrials.gov Identifier: NCT03905525 |
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Recruitment Status :
Active, not recruiting
First Posted : April 5, 2019
Last Update Posted : January 13, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Sjögren Syndrome | Drug: CFZ533 Other: Placebo | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 273 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 |
| Actual Primary Completion Date : | September 28, 2022 |
| Estimated Study Completion Date : | June 5, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort 1 /Arm A
CFZ533 dose 1
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Drug: CFZ533
Biological
Other Name: iscalimab |
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Experimental: Cohort 1/Arm B
CFZ533 dose 2
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Drug: CFZ533
Biological
Other Name: iscalimab |
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Experimental: Cohort 1/Arm C
CFZ533 dose 3
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Drug: CFZ533
Biological
Other Name: iscalimab |
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Placebo Comparator: Cohort 1/Arm D
Placebo dose (up to week 24)
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Other: Placebo
liquid placebo for injections |
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Experimental: Cohort 1/Arm D1
CFZ533 dose 1 (from week 24)
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Drug: CFZ533
Biological
Other Name: iscalimab |
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Experimental: Cohort 2/Arm E
CFZ533 dose 1
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Drug: CFZ533
Biological
Other Name: iscalimab |
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Placebo Comparator: Cohort 2/Arm F
Placebo dose (up to week 24)
|
Other: Placebo
liquid placebo for injections |
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Experimental: Cohort 2/Arm F1
CFZ533 dose 2 (from week 24)
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Drug: CFZ533
Biological
Other Name: iscalimab |
- 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
- Change from baseline in ESSPRI at Week 24 [ Time Frame: 24 weeks ]Cohort 1 - Efficacy (Patient Reported Outcomes)
- 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)
- Change from baseline in Physician Global Assessment (PhGA) at Week 24 [ Time Frame: 24 weeks ]Cohort 1&2 - Efficacy (Clinical Outcome Measures)
- Change from baseline in ESSDAI at Week 24 [ Time Frame: 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. [ Time Frame: 24 weeks ]Cohort 2 - Efficacy (Patient Reported Outcomes)
- 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
- Serum Free Light Chain (FLC) levels at analysis visit up to end of study [ Time Frame: 60 weeks ]Cohort 1&2 - Biomarkers (1)
- Immunoglobulin IgG and IgM levels at analysis visits up to end of study [ Time Frame: 60 weeks ]Cohort 1&2 - Biomarkers (2)
- 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)
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.
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts 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.
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
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| Study Director: | Study Director Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT03905525 |
| Other Study ID Numbers: |
CCFZ533B2201 |
| First Posted: | April 5, 2019 Key Record Dates |
| Last Update Posted: | January 13, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Sjögren fatigue dryness anti-CD40 |
CFZ533 iscalimab TWINSS autoimmune |
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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 |