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NCT04541589: TWINSS Extn

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

Completed Phase 2 Results posted Last updated 16 October 2025
What this trial tests

Phase 2 trial testing Iscalimab in Sjogren's Syndrome in 206 participants. Completed in 19 August 2024.

Timeline
5 January 2021
Primary endpoint
19 August 2024
19 August 2024

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment206
Start date5 January 2021
Primary completion19 August 2024
Estimated completion19 August 2024
Sites62 locations across Italy, Colombia, Japan, South Korea, Netherlands, Russia, Sweden, Portugal

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 99, any sex, with Sjogren's Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) Primary · 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

Death
GroupValue95% CI
Arm 1: Iscalimab 600 mg0
Arm 2 - Iscalimab 300 mg0
Adverse event (all severities)
GroupValue95% CI
Arm 1: Iscalimab 600 mg127
Arm 2 - Iscalimab 300 mg43
Adverse Event- Mild
GroupValue95% CI
Arm 1: Iscalimab 600 mg57
Arm 2 - Iscalimab 300 mg24
Adverse Event- Moderate
GroupValue95% CI
Arm 1: Iscalimab 600 mg62
Arm 2 - Iscalimab 300 mg17
Adverse Event- Severe
GroupValue95% CI
Arm 1: Iscalimab 600 mg8
Arm 2 - Iscalimab 300 mg2
Serious Adverse Event
GroupValue95% CI
Arm 1: Iscalimab 600 mg13
Arm 2 - Iscalimab 300 mg2
Adverse Event leading to study medication discontinuation
GroupValue95% CI
Arm 1: Iscalimab 600 mg8
Arm 2 - Iscalimab 300 mg2
Free Iscalimab Concentration in Plasma Secondary · 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).

Day 1
GroupValue95% CI
Arm 1: Iscalimab 600 mg3.56± 372.2
Arm 2 - Iscalimab 300 mg451.8± 0.751
Day 113
GroupValue95% CI
Arm 1: Iscalimab 600 mg125± 62.7
Arm 2 - Iscalimab 300 mg56.9± 54.0
Day 225
GroupValue95% CI
Arm 1: Iscalimab 600 mg126± 104.7
Arm 2 - Iscalimab 300 mg50.3± 57.0
Day 337
GroupValue95% CI
Arm 1: Iscalimab 600 mg138± 69.3
Arm 2 - Iscalimab 300 mg62.6± 63.3
Day 421
GroupValue95% CI
Arm 1: Iscalimab 600 mg4.47± 533.7
Arm 2 - Iscalimab 300 mg350.4± 0.336
Incidence of Anti-iscalimab Antibodies in Plasma Secondary · 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).

GroupValue95% CI
Arm 1: Iscalimab 600 mg1
Arm 2 - Iscalimab 300 mg2

Adverse events — posted to ClinicalTrials.gov

Time frame: 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. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm 1: Iscalimab 600 mg
Serious: 13/152 (9%)
Deaths: 0/152
Arm 2 - Iscalimab 300 mg
Serious: 2/54 (4%)
Deaths: 0/54

Serious adverse events (17 terms)

ReactionSystemArm 1: Iscalimab 600 mgArm 2 - Iscalimab 300 mg
Febrile neutropeniaBlood and lymphatic system disorders
GranulocytopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
GlaucomaEye disorders
Anal prolapseGastrointestinal disorders
CholangitisHepatobiliary disorders
Food allergyImmune system disorders
BartholinitisInfections and infestations
COVID-19Infections and infestations
COVID-19 pneumoniaInfections and infestations
Sjogren's syndromeMusculoskeletal and connective tissue disorders
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Status epilepticusNervous system disorders
Adjustment disorder with depressed moodPsychiatric disorders
DepressionPsychiatric disorders
PleurisyRespiratory, thoracic and mediastinal disorders
Other adverse events (15 terms — click to expand)

ReactionSystemArm 1: Iscalimab 600 mgArm 2 - Iscalimab 300 mg
COVID-19Infections and infestations
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
InfluenzaInfections and infestations
Oral herpesInfections and infestations
SinusitisInfections and infestations
OsteoarthritisMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Febrile neutropenia, Granulocytopenia, Neutropenia, Glaucoma, Anal prolapse, Cholangitis, Food allergy, Bartholinitis.

Data from ClinicalTrials.gov NCT04541589 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. New developments in Sjogren's syndrome.
    Thalayasingam N, Baldwin K, Judd C, Ng WF. · · 2021 · cited 25× · PMID 34951923 · DOI 10.1093/rheumatology/keab466
  2. Disrupting B and T-cell collaboration in autoimmune disease: T-cell engagers versus CAR T-cell therapy?
    Shah K, Leandro M, Cragg M, Kollert F, et al · · 2024 · cited 23× · PMID 38642912 · DOI 10.1093/cei/uxae031
  3. Emerging treatment for Sjögren's disease: a review of recent phase II and III trials.
    Fox RI, Fox CM, McCoy SS. · · 2023 · cited 9× · PMID 37127914 · DOI 10.1080/14728214.2023.2209720
  4. New molecular targets in the treatment of rheumatoid arthritis.
    Wallace BI, Cooney L, Fox DA. · · 2024 · cited 7× · PMID 38165286 · DOI 10.1097/bor.0000000000001000
  5. Sjögren's Syndrome: Epidemiology, Classification Criteria, Molecular Pathogenesis, Diagnosis, and Treatment.
    Hu Y, Wen B, Zhang Y, Wang X, et al · · 2025 · cited 3× · PMID 40656544 · DOI 10.1002/mco2.70297

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04541589.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing