Clinical Trial Results:
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
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Summary
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EudraCT number |
2020-001942-20 |
Trial protocol |
HU GR DE PT FR NL IT SE |
Global end of trial date |
19 Aug 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jun 2025
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First version publication date |
28 Jun 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CCFZ533B2201E1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04541589 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
Novartis Campus,, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Aug 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Aug 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study is to evaluate the safety and tolerability of iscalimab at two dose levels (600 mg and 300 mg) in patients with Sjögren’s Syndrome, who participated in the TWINSS core study (CCFZ533B2201)
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Jan 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 5
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Country: Number of subjects enrolled |
Australia: 1
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Country: Number of subjects enrolled |
Austria: 11
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Country: Number of subjects enrolled |
Brazil: 8
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Country: Number of subjects enrolled |
Canada: 5
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Country: Number of subjects enrolled |
Chile: 21
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Country: Number of subjects enrolled |
Colombia: 7
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Germany: 19
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Country: Number of subjects enrolled |
Greece: 2
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Country: Number of subjects enrolled |
Hungary: 12
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Country: Number of subjects enrolled |
Israel: 7
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Japan: 14
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Country: Number of subjects enrolled |
Korea, Republic of: 5
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Country: Number of subjects enrolled |
Netherlands: 8
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Country: Number of subjects enrolled |
Portugal: 9
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Country: Number of subjects enrolled |
Romania: 6
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Country: Number of subjects enrolled |
Russian Federation: 30
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Country: Number of subjects enrolled |
Sweden: 1
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Country: Number of subjects enrolled |
Türkiye: 3
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Country: Number of subjects enrolled |
United Kingdom: 7
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Country: Number of subjects enrolled |
United States: 16
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Worldwide total number of subjects |
206
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EEA total number of subjects |
77
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
171
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From 65 to 84 years |
35
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants who completed the core study (CCFZ533B2201, NCT03905525) 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 were enrolled in this study | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer, Data analyst, Assessor | ||||||||||||||||||||||||
Blinding implementation details |
The study was conducted as a double-blind treatment until the final database lock of the Core study (NCT03905525). During this period, participants, Investigator, site staff, and persons performing the assessments remained blinded to the identity of the treatment until the final database lock of the core study
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Arm 1: Iscalimab 600 mg | ||||||||||||||||||||||||
Arm description |
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 type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Iscalimab
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Investigational medicinal product code |
CFZ533
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Iscalimab 600 mg or 300 mg was administered subcutaneously weekly for the first 3 weeks. Subsequently, iscalimab was administered subcutaneously bi-weekly (every other week or Q2W).
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Arm title
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Arm 2 - Iscalimab 300 mg | ||||||||||||||||||||||||
Arm description |
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 type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo (1 injection of 2 ml) administered to participants in the iscalimab 300 mg arm to mantain blinding until the final database lock of the core study
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Investigational medicinal product name |
Iscalimab
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Investigational medicinal product code |
CFZ533
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Iscalimab 600 mg or 300 mg was administered subcutaneously weekly for the first 3 weeks. Subsequently, iscalimab was administered subcutaneously bi-weekly (every other week or Q2W).
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Baseline characteristics reporting groups
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Reporting group title |
Arm 1: Iscalimab 600 mg
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Reporting group description |
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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm 2 - Iscalimab 300 mg
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm 1: Iscalimab 600 mg
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Reporting group description |
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). | ||
Reporting group title |
Arm 2 - Iscalimab 300 mg
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Reporting group description |
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. | ||
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End point title |
Number of participants with Treatment-emergent adverse events (TEAEs) [1] | ||||||||||||||||||||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
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
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were planned for this primary end point. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Free iscalimab concentration in plasma | |||||||||||||||||||||||||||
End point description |
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).
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End point type |
Secondary
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End point timeframe |
Predose at Day 1, 113, 225, 337 and 421
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End point title |
Incidence of anti-iscalimab antibodies in plasma | |||||||||
End point description |
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).
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End point type |
Secondary
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End point timeframe |
60 weeks
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
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
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Adverse event reporting additional description |
Any sign or symptom that occurred during the conduct of the trial and safety follow-up. The safety analyses were done on the safety population, which included all randomized subjects who received at least one dose of study medication. Patients were analyzed according to the actual treatment received.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Arm 2 - Iscalimab 300 mg
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Arm 1: Iscalimab 600 mg
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Reporting group description |
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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Feb 2021 |
The main purpose of the amendment was to include an
additional assessment time point as part of the IRT algorithm criteria for participant rollover
from the TWINSS core study (CCFZ533B2201) to extension study. ESSDAI and ESSPRI
scores at Week 0 might be used for the IRT algorithm in the absence of a score at Week 4 of
the core study. Specific guidance concerning public health emergency situations as declared by
local or regional authorities (i.e., pandemic, epidemic or natural disaster) was also included. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
