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NCT02291029

Safety, Pharmacokinetics and Preliminary Efficacy Study of CFZ533 in Patients With Primary Sjögren's Syndrome

Completed Phase 2 Results posted Last updated 5 January 2021
What this trial tests

Phase 2 trial testing CFZ533 active - Cohort 1 in Primary Sjögren's Syndrome in 69 participants. Completed in 29 June 2018.

Timeline
22 October 2014
Primary endpoint
29 June 2018
29 June 2018

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment69
Start date22 October 2014
Primary completion29 June 2018
Estimated completion29 June 2018
Sites9 locations across United Kingdom, Germany, Hungary, Switzerland, United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Primary Sjögren'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.

Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Primary · Baseline and Week 12

The effect of CFZ533 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123). A reduction from baseline indicates improvement in patients.

Baseline
GroupValue95% CI
Cohort 1 CFZ53312.0± 3.78
Cohort 1 Placebo11.8± 3.86
Cohort 2 CFZ53310.6± 4.44
Cohort 2 Placebo11.0± 5.16
Cohort 3 CFZ533 Arm 112.7± 6.06
Cohort 3 CFZ533 Arm 210.4± 5.87
Week 12
GroupValue95% CI
Cohort 1 CFZ5339.6± 5.45
Cohort 1 Placebo9.8± 3.30
Cohort 2 CFZ5334.2± 4.25
Cohort 2 Placebo9.7± 9.05
Cohort 3 CFZ533 Arm 17.2± 6.69
Cohort 3 CFZ533 Arm 22.8± 2.48
Change from Baseline to Week 12
GroupValue95% CI
Cohort 1 CFZ533-2.4± 2.77
Cohort 1 Placebo-2.0± 2.45
Cohort 2 CFZ533-6.4± 4.00
Cohort 2 Placebo-1.3± 8.06
Cohort 3 CFZ533 Arm 1-5.5± 5.49
Cohort 3 CFZ533 Arm 2-7.6± 7.14
Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Intensity (ESSPRI) Secondary · Baseline and Week 12

The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms.

Baseline
GroupValue95% CI
Cohort 1 CFZ5336.75± 1.909
Cohort 1 Placebo7.00± 1.826
Cohort 2 CFZ5336.71± 1.678
Cohort 2 Placebo7.18± 1.486
Cohort 3 CFZ533 Arm 17.00± 1.604
Cohort 3 CFZ533 Arm 26.00± 2.344
Week 12
GroupValue95% CI
Cohort 1 CFZ5335.71± 1.240
Cohort 1 Placebo7.08± 2.251
Cohort 2 CFZ5335.03± 2.413
Cohort 2 Placebo6.24± 2.039
Cohort 3 CFZ533 Arm 15.33± 2.269
Cohort 3 CFZ533 Arm 24.83± 2.552
Change from Baseline to Week 12
GroupValue95% CI
Cohort 1 CFZ533-1.04± 1.201
Cohort 1 Placebo0.08± 0.631
Cohort 2 CFZ533-1.68± 1.954
Cohort 2 Placebo-0.94± 1.246
Cohort 3 CFZ533 Arm 1-1.67± 1.841
Cohort 3 CFZ533 Arm 2-1.17± 2.333
Change From Baseline in Physician Global Assessment of the Patient's Overall Disease Activity (VAS) Secondary · Baseline and Week 12

The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

Baseline
GroupValue95% CI
Cohort 1 CFZ53357.9± 15.72
Cohort 1 Placebo57.8± 17.19
Cohort 2 CFZ53351.9± 12.62
Cohort 2 Placebo47.9± 19.18
Cohort 3 CFZ533 Arm 150.4± 12.39
Cohort 3 CFZ533 Arm 247.1± 18.34
Week 12
GroupValue95% CI
Cohort 1 CFZ53340.5± 16.42
Cohort 1 Placebo55.5± 12.01
Cohort 2 CFZ53322.8± 11.78
Cohort 2 Placebo34.2± 13.90
Cohort 3 CFZ533 Arm 125.4± 16.65
Cohort 3 CFZ533 Arm 227.3± 16.74
Change from Baseline to Week 12
GroupValue95% CI
Cohort 1 CFZ533-17.6± 24.60
Cohort 1 Placebo-2.3± 10.90
Cohort 2 CFZ533-28.7± 16.02
Cohort 2 Placebo-13.7± 22.97
Cohort 3 CFZ533 Arm 1-25.0± 15.30
Cohort 3 CFZ533 Arm 2-19.8± 21.96
Change From Baseline in Patient's Global Assessment of Their Disease Activity (VAS) Secondary · Baseline and Week 12

The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

Baseline
GroupValue95% CI
Cohort 1 CFZ53347.13± 32.406
Cohort 1 Placebo73.00± 12.623
Cohort 2 CFZ53358.43± 19.881
Cohort 2 Placebo54.91± 21.002
Cohort 3 CFZ533 Arm 163.69± 25.799
Cohort 3 CFZ533 Arm 252.08± 22.138
Week 12
GroupValue95% CI
Cohort 1 CFZ53349.06± 24.519
Cohort 1 Placebo75.50± 24.393
Cohort 2 CFZ53334.85± 24.564
Cohort 2 Placebo42.27± 24.483
Cohort 3 CFZ533 Arm 138.46± 26.965
Cohort 3 CFZ533 Arm 253.17± 25.305
Change from Baseline to Week 12
GroupValue95% CI
Cohort 1 CFZ5331.94± 26.023
Cohort 1 Placebo2.50± 17.861
Cohort 2 CFZ533-23.05± 26.920
Cohort 2 Placebo-12.64± 26.871
Cohort 3 CFZ533 Arm 1-25.23± 29.833
Cohort 3 CFZ533 Arm 21.08± 23.283
Change From Baseline in Short Form (36) Health Survey (SF-36) Physical Component Score Secondary · Baseline and Week 12

The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.

Baseline
GroupValue95% CI
Cohort 1 CFZ53342.218± 6.9437
Cohort 1 Placebo31.215± 12.5562
Cohort 2 CFZ53338.163± 8.5905
Cohort 2 Placebo38.819± 5.9689
Week 12
GroupValue95% CI
Cohort 1 CFZ53340.374± 9.2230
Cohort 1 Placebo36.123± 13.0002
Cohort 2 CFZ53344.001± 9.3943
Cohort 2 Placebo40.298± 8.9392
Change from Baseline to Week 12
GroupValue95% CI
Cohort 1 CFZ533-1.005± 4.5380
Cohort 1 Placebo4.908± 4.2349
Cohort 2 CFZ5335.546± 7.1760
Cohort 2 Placebo1.479± 8.2497
Change From Baseline in Short Form (36) Health Survey (SF-36) Mental Component Score Secondary · Baseline and Week 12

The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.

Baseline
GroupValue95% CI
Cohort 1 CFZ53346.838± 7.8986
Cohort 1 Placebo43.118± 16.3701
Cohort 2 CFZ53337.071± 12.2914
Cohort 2 Placebo39.512± 15.4212
Week 12
GroupValue95% CI
Cohort 1 CFZ53348.076± 12.5197
Cohort 1 Placebo43.660± 13.9997
Cohort 2 CFZ53344.688± 10.2469
Cohort 2 Placebo43.785± 13.2982
Change from Baseline to Week 12
GroupValue95% CI
Cohort 1 CFZ5330.373± 6.3174
Cohort 1 Placebo0.543± 4.0309
Cohort 2 CFZ5338.212± 11.1378
Cohort 2 Placebo4.273± 10.7671
Change From Baseline in Multidimensional Fatigue Inventory (MFI) Secondary · Baseline and Week 12

The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a possible range from 4-20. The reported total score has a range from 20-100. A reduction from baseline in MFI indicates improvement.

Baseline
GroupValue95% CI
Cohort 1 CFZ53354.1± 16.23
Cohort 1 Placebo78.0± 17.80
Cohort 2 CFZ53370.0± 17.51
Cohort 2 Placebo66.2± 17.59
Week 12
GroupValue95% CI
Cohort 1 CFZ53353.5± 13.96
Cohort 1 Placebo69.8± 17.75
Cohort 2 CFZ53355.2± 16.65
Cohort 2 Placebo63.3± 16.99
Change from Baseline to Week 12
GroupValue95% CI
Cohort 1 CFZ533-0.6± 8.12
Cohort 1 Placebo-8.3± 8.18
Cohort 2 CFZ533-14.5± 18.09
Cohort 2 Placebo-2.9± 12.37

Adverse events — posted to ClinicalTrials.gov

Time frame: Cohort 1 and 2: 255 days (30 days post study completion) Cohort 3: 171 days (30 days post study completion). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 CFZ533
Serious: 1/8 (13%)
Deaths: 0/8
Cohort 1 Placebo
Serious: 0/4 (0%)
Deaths: 0/4
Cohort 2 CFZ533
Serious: 1/21 (5%)
Deaths: 0/21
Cohort 2 Placebo
Serious: 0/11 (0%)
Deaths: 0/11
Cohort 3 CFZ533 Arm 1
Serious: 0/13 (0%)
Deaths: 0/13
Cohort 3 CFZ533 Arm 2
Serious: 1/12 (8%)
Deaths: 0/12

Serious adverse events (5 terms)

ReactionSystemCohort 1 CFZ533Cohort 1 PlaceboCohort 2 CFZ533Cohort 2 PlaceboCohort 3 CFZ533 Arm 1Cohort 3 CFZ533 Arm 2
Atrial fibrillationCardiac disorders
Conjunctivitis bacterialInfections and infestations
Post procedural swellingInjury, poisoning and procedural complications
Procedural painInjury, poisoning and procedural complications
HaemarthrosisMusculoskeletal and connective tissue disorders
Other adverse events (162 terms — click to expand)

ReactionSystemCohort 1 CFZ533Cohort 1 PlaceboCohort 2 CFZ533Cohort 2 PlaceboCohort 3 CFZ533 Arm 1Cohort 3 CFZ533 Arm 2
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
VomitingGastrointestinal disorders
Injection site haematomaGeneral disorders
BronchitisInfections and infestations
Lower respiratory tract infectionInfections and infestations
Oral herpesInfections and infestations
Urinary tract infectionInfections and infestations
ContusionInjury, poisoning and procedural complications
Lipase increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
Increased tendency to bruiseBlood and lymphatic system disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
LymphadenopathyBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
PalpitationsCardiac disorders
Cerumen impactionEar and labyrinth disorders
DeafnessEar and labyrinth disorders
HypoacusisEar and labyrinth disorders
TinnitusEar and labyrinth disorders
BlepharitisEye disorders
CataractEye disorders
DiplopiaEye disorders
Dry eyeEye disorders
Eye painEye disorders
Ocular hyperaemiaEye disorders
Vitreous detachmentEye disorders
Vitreous floatersEye disorders
Abdominal discomfortGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders

Most-reported serious reactions: Atrial fibrillation, Conjunctivitis bacterial, Post procedural swelling, Procedural pain, Haemarthrosis.

Data from ClinicalTrials.gov NCT02291029 adverse events section.

Sponsor's own description

This study did evaluate the safety,tolerability and preliminary therapeutic efficacy of multiple doses of intravenous infusion of CFZ533 monoclonal antibody in patients with primary Sjögren's syndrome(pSS)

Publications & conference data

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

  1. Kinase inhibition in autoimmunity and inflammation.
    Zarrin AA, Bao K, Lupardus P, Vucic D. · · 2021 · cited 302× · PMID 33077936 · DOI 10.1038/s41573-020-0082-8
  2. Current State of Knowledge on Primary Sjögren's Syndrome, an Autoimmune Exocrinopathy.
    Parisis D, Chivasso C, Perret J, Soyfoo MS, et al · · 2020 · cited 114× · PMID 32698400 · DOI 10.3390/jcm9072299
  3. Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren's syndrome: a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study.
    Fisher BA, Szanto A, Ng WF, Bombardieri M, et al · · 2020 · cited 76× · PMID 38263652 · DOI 10.1016/s2665-9913(19)30135-3
  4. Innate Immunity and Biological Therapies for the Treatment of Sjögren's Syndrome.
    Srivastava A, Makarenkova HP. · · 2020 · cited 40× · PMID 33271951 · DOI 10.3390/ijms21239172
  5. Recent advances in kidney transplantation: a viewpoint from the Descartes advisory board.
    Abramowicz D, Oberbauer R, Heemann U, Viklicky O, et al · · 2018 · cited 40× · PMID 29342289 · DOI 10.1093/ndt/gfx365
  6. Autoimmune manifestations in aged mice arise from early-life immune dysregulation.
    Mahmoud TI, Wang J, Karnell JL, Wang Q, et al · · 2016 · cited 38× · PMID 27798262 · DOI 10.1126/scitranslmed.aag0367
  7. New developments in Sjogren's syndrome.
    Thalayasingam N, Baldwin K, Judd C, Ng WF. · · 2021 · cited 25× · PMID 34951923 · DOI 10.1093/rheumatology/keab466
  8. Biological Therapy in Primary Sjögren's Syndrome: Effect on Salivary Gland Function and Inflammation.
    Chowdhury F, Tappuni A, Bombardieri M. · · 2021 · cited 13× · PMID 34336905 · DOI 10.3389/fmed.2021.707104

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