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

Phase 2

Completed

Conditions: Sjogren's Syndrome

Interventions: Drug: Iscalimab
Other: Placebo

Registration Number: NCT04541589

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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: This study was a continuation of the TWINSS core study CCFZ533B2201 (NCT03905525) that offered continuation of treatment for participants who completed the core study and were deemed by the Investigator to clinically benefit from continued iscalimab therapy based upon response to therapy at the end of the treatment period of the core study. The extension study was a 48-week treatment study, with a safety follow-up period of 12 weeks, to provide additional safety and tolerability information for iscalimab.At Week 60 of the TWINSS core study, eligible participants had the option to enroll in the extension study.

Participants were classified as treatment responders or non-responder based on their European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI) and EULAR Sjögren's syndrome patient reported index (ESSPRI) scores from predefined time points in the core study. In the extension study, participants were reassigned to either iscalimab 600 mg or 300 mg subcutaneously via prefilled syringes (PFS) based on their responder status and the iscalimab doses that they received in the core study

All participants enrolled in the extension study received a weekly loading regimen at the start of the treatment period for the initial 3 weeks, followed by a subcutaneous maintenance regimen (600 or 300 mg subcutaneously every 2 weeks). Injections were performed at site or at home by site staff or participant/caregiver.

Study blinding for the extension study was maintained until final database lock of the core study, upon which the participants and Investigators were unblinded, making it an open-label study through Week 120 (end of study visit).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 206

Inclusion Criteria

Participants had to have participated in the TWINSS core study, CCFZ533B2201 (NCT03905525), and had to have completed the entire treatment period up to Week 48 and the follow-up period up to Week 60.
Signed informed consent had to be obtained prior to participation in the Extension study (i.e., before commencement of the Week 60 assessments of the core study).
In the judgment of the Investigator, participants had to be expected to clinically benefit from continued iscalimab therapy.

Exclusion Criteria

Sjögren's Syndrome overlap syndromes where another autoimmune rheumatic disease constituted the principle illness, specifically:
- Moderate-to-severe active systemic lupus erythematosus (SLE) with anti-dsDNA positivity and renal involvement, or other organ involvement that impeded on the ability to score ESSDAI domains
- Active rheumatoid arthritis (RA) that impeded 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 was active and required 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 was 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 were using highly effective methods of contraception during dosing and for 14 weeks after stopping the 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: Iscalimab 600 mg	Iscalimab	Participants received 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously weekly for the initial 3 weeks as loading doses, followed by a bi-weekly maintenance regimen at 600 mg (2 injections of 300 mg/2 mL).
Arm 2 - Iscalimab 300 mg	Iscalimab	Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.
Arm 2 - Iscalimab 300 mg	Placebo	Participants received one dose of 600 mg (2 injections of 300 mg/2 mL) of iscalimab subcutaneously on the first day of the extension study; then 300 mg weekly (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo) for the next 2 weeks as loading doses. This was followed by a bi-weekly maintenance regimen of 300 mg (1 injection of 300 mg/2 mL of iscalimab and 1 injection of 2 mL of placebo). After the final database lock of the core study, participants underwent unblinding, leading to the discontinuation of placebo injections.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From start of extension study up to 14 weeks after last study-drug administration or end of study (whichever occurred earlier), assessed up to approximately 60 weeks	An AE was defined as any untoward medical occurrence (e.g., any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a participant. TEAE included all AEs up to the last dose date plus 14 weeks or the end of the entire study (including the safety follow-up period), whichever occurred earlier. A patient with multiple severity ratings for an AE was only counted under the maximum rating. Additionally, a patient with multiple occurrences of an event was counted only once. The severity of AEs was assessed using the Common Terminology Criteria for Adverse Events, with the following grading system: Mild: usually transient in nature and generally not interfering with normal activities; Moderate: sufficiently discomforting to interfere with normal activities; Severe: prevented normal activities. A serious adverse event (SAE) was defined as any AE that required medical intervention, hospitalization, or results in death, disability, or a birth defect.

Secondary Outcome Measures

Name	Time	Method
Free Iscalimab Concentration in Plasma	Predose at Day 1, 113, 225, 337 and 421	Free iscalimab concentration in plasma during the treatment (Ctrough) and follow-up (up to end of study) periods. Blood sample was collected at the specified timepoints to assess the concentration of free iscalimab. The baseline assessment of this extension study (Day 1) was identical to the last timepoint (FUP3/Week 60) of the core study (CCFZ533B2201).
Incidence of Anti-iscalimab Antibodies in Plasma	60 weeks	Number of participants with anti-iscalimab antibodies (ADA) in plasma at any time during the study. The baseline assessment of this extension study (Day 1) was identical to the last timepoint (FUP3/Week 60) of the core study (CCFZ533B2201).

Trial Locations

Locations (8): North GA Rheumatology Group PC
🇺🇸
Suwanee, Georgia, United States
Ochsner Health System
🇺🇸
Baton Rouge, Louisiana, United States
The John Hopkins Jerome L Greene Sjogren
🇺🇸
Baltimore, Maryland, United States
Tufts School of Dental Medicine
🇺🇸
Boston, Massachusetts, United States
Winthrop University Hospital
🇺🇸
Mineola, New York, United States
Perelman School of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
Uni Wisconsin School Med Pub Health
🇺🇸
Madison, Wisconsin, United States
Novartis Investigative Site
🇬🇧
Manchester, United Kingdom
North GA Rheumatology Group PC
🇺🇸Suwanee, Georgia, United States