Study of Safety and Tolerability of CFZ533 in Patients With Sjögren's Syndrome

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of iscalimab at two dose levels in patients with Sjögren's Syndrome, who participated in the TWINSS core study, CCFZ533B2201(NCT03905525). Additionally, this Extension study will further explore the pharmacokinetics (PK) and efficacy of iscalimab at two dose level.

Detailed Description
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This Extension study is a 48-week treatment study, with a safety follow-up period of 12 weeks. This study will evaluate the safety and tolerability of iscalimab at two dose levels in patients with Sjögren's Syndrome, who must have participated in the TWINSS core study, CCFZ533B2201 (NCT03905525) and must have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60. Study treatment will be administered as bi-weekly subcutaneous injections (Q2W s.c.) via prefilled syringes (PFS).

Official Title
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A TWINSS Extension Trial to Evaluate the Safety and Tolerability of CFZ533 (Iscalimab) at Two Dose Levels Administered Subcutaneously in Patients With Sjögren's Syndrome

Conditions
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Sjogren's Syndrome

Intervention / Treatment
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* Drug: CFZ533 (iscalimab)
* Other: CFZ533 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants eligible for inclusion in this study must meet all of the following criteria: Participants must have participated in the TWINSS core study, CCFZ533B2201 (NCT03905525), and must have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60 Signed informed consent must be obtained prior to participation in the Extension study (i.e. before commencement of the Week 60 assessments of the core study) In the judgement of the Investigator, participants must be expected to clinically benefit from continued iscalimab therapy Exclusion Criteria: Participants meeting any of the following criteria are not eligible for inclusion in this study. Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constitutes the principle illness, specifically: Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA positivity and renal involvement, or other organ involvement that impedes on ability to score ESSDAI domains Active rheumatoid arthritis (RA) that impedes on the ability to score the ESSDAI articular domain Systemic sclerosis Any other concurrent connective tissue disease (e.g., lupus nephritis (LN), large vessel vasculitis (LVV), Sharp syndrome (mixed connective tissue disease) that is active and requires immunosuppressive treatment outside the scope of this trial and would impede on Sjögren's Syndrome organ domain assessments Use of other investigational drugs other than iscalimab during the core study Active uncontrolled viral, bacterial or other infections requiring systemic treatment at the time of enrollment, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 14 weeks after stopping of investigational drug. Missing ESSDAI (Cohort 1 and Cohort 2) or ESSPRI (Cohort 2) scores in the core study at Weeks 0 and 4 or Weeks 40 and 48.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Upon completion of the core study (NCT03905525), Investigators will use their clinical judgment including responder definitions to decide if it is beneficial for participants to continue with the Extension study based upon response to therapy at the end of the treatment period of the core study. Participants will be re-assigned to one of the following two treatment arms: Arm 1 - Iscalimab Dose 1 s.c. Q2W Arm 2 - Iscalimab Dose 2 s.c. Q2W and Placebo At Week 60 of the TWINSS core study (NCT03905525), all eligible participants from the core study can opt to be enrolled in the extension study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Arm 1 - Iscalimab Dose 1 | Drug: CFZ533 (iscalimab)<br>* Biological<br>* Other names: iscalimab;|
| Active Comparator: Arm 2<br>Arm 2 - Iscalimab Dose 2 and Placebo | Drug: CFZ533 (iscalimab)<br>* Biological<br>* Other names: iscalimab;Other: CFZ533 Placebo<br>* Matching placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent adverse events (TEAEs) | Number and percentage of participants having any AE | 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Free iscalimab concentration in plasma during the treatment (Ctrough) and follow-up (up to end of study) periods | To assess the pharmacokinetics (PK trough levels) | 60 weeks | 
| Incidence of anti-iscalimab antibodies in plasma at analysis visits up to end of study | To assess immunogenicity of iscalimab | 60 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sjogren's Syndrome, autoimmune, ESSDAI, ESSPRI, anti-CD40, CFZ533, iscalimab, TWINSS Extension