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NCT02565576

Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis

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

Phase 2 trial testing Placebo in Myasthenia Gravis, Generalized in 44 participants. Completed in 19 December 2017.

Timeline
29 September 2015
Primary endpoint
31 July 2017
19 December 2017

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment44
Start date29 September 2015
Primary completion31 July 2017
Estimated completion19 December 2017
Sites15 locations across Denmark, Russia, Taiwan, Germany, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 85, any sex, with Myasthenia Gravis, Generalized. 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.

Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type. Primary · week 25

QMG score is an established validated measure of disease severity used in MG trials (Jaretzki et al 2000). The scoring system is based on quantitative testing of sentinel muscle groups by means of a 4 point scale ranging from 0 (no symptoms) to 3 (severe symptoms). The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and the total score ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits) (Sharshar et al 2000, Bedlack et al 2005).

GroupValue95% CI
CFZ533-4.07-5.67 – -2.47
Placebo-2.93-4.53 – -1.33
Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type. Secondary · From baseline to week 49

The Myasthenia Gravis Composite (MGC) score is another key efficacy outcome measure, ranging from 0 to 50. It is reliable and demonstrates concurrent and longitudinal construct validity in the MG practice care setting (Burns et al 2010). The MGC scale covers 10 important functional domains most frequently involved in patients with MG. The proportion of bulbar and respiratory items reflect the clinical importance of these domains in the disease, and are appropriately weighted. The assessment of each of the 10 test items provides immediate insight into the status of that particular functional d

GroupValue95% CI
CFZ533-8.00-9.83 – -6.16
Placebo-5.62-7.45 – -3.78
Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score Secondary · at week 49

QMG score is an established validated measure of disease severity used in MG trials (Jaretzki et al 2000). The scoring system is based on quantitative testing of sentinel muscle groups by means of a 4 point scale ranging from 0 (no symptoms) to 3 (severe symptoms). The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and the total score ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits) (Sharshar et al 2000, Bedlack et al 2005).

improvement by ≥ 3 points in the QMG score
GroupValue95% CI
CFZ53310
Placebo9
worsening by ≥ 3 points in the QMG score
GroupValue95% CI
CFZ5332
Placebo2
Proportion of Patients Intolerant to Steroid Taper Secondary · week 49
GroupValue95% CI
CFZ533NA
PlaceboNA
Number of Patients Who Discontinued Due to Inefficacy or Worsening Secondary · week 49
GroupValue95% CI
CFZ5330
Placebo0
Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Secondary · week 25

The MG-ADL is an 8-item survey to assess functional performance of daily activities that are sometimes impaired by MG e.g. talking, breathing, swallowing etc. (Muppidi et al 2011). The higher score on MG-ADL scale (0-24 points) indicates worse functional performance of daily activities.

GroupValue95% CI
CFZ533-2.6± 2.97
Placebo-1.1± 3.23
Mean Changes From Baseline in the QMG Score at Week 49 Secondary · week 49

QMG (quantitative myasthenia gravis) score is an established validated measure of disease severity used in MG trials (Jaretzki et al 2000). The scoring system is based on quantitative testing of sentinel muscle groups by means of a 4 point scale ranging from 0 (no symptoms) to 3 (severe symptoms). The scale measures ocular, bulbar, respiratory, and limb function, grading each finding, and the total score ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits) (Sharshar et al 2000, Bedlack et al 2005). A decrease in the QMG score indicated an improvement. Results given as a c

GroupValue95% CI
CFZ533-2.9± 5.16
Placebo-2.6± 4.30
Mean Change From Baseline in the Myasthenia Gravis Quality of Life (MG QOL-15) Secondary · week 25

The MG-QOL15 is a 15-item survey, completed by MG patients and it is designed to assess some aspects of quality of life (QoL) related to MG (Burns et al 2011) e.g. assesment of mood, eating, speaking, driving a car etc.. The higher score on MG-QOL15 scale (0-60 points) indicates worse QoL.

GroupValue95% CI
CFZ533-9.7± 11.0
Placebo-6.7± 10.86
Free CD40 on B Cells Secondary · week 1, week 25

CD40 receptor occupancy by CFZ533 in peripheral blood was assessed by flow cytometry analysis, measuring free or total CD40 receptors on whole blood B cells. Free CD40 on CD19-positive B cells, using PE-conjugated CFZ533 whose binding was prevented by bound, unconjugated CFZ533 (drug bound to CD40 on peripheral blood B cells). The more CD40 was occupied by unlabeled CFZ533, the less binding of labeled CFZ533, manifest as a lower mean fluorescence intensity (MFI) of CD40 on B cells. MFI from free CD40 on B cells was converted into Molecules of Equivalent Soluble Fluorochrome (MESF) using PE-MES

Free CD40 on B cells week 1 predose
GroupValue95% CI
CFZ53334242.9± 18455.80
Placebo31025.9± 16138.97
Free CD40 on B cells week 25
GroupValue95% CI
CFZ5335259.1± 11341.57
Placebo24908.3± 5022.03
Total Soluble CD40 (sCD40) in Plasma Secondary · week1, week 25

PD

week 1
GroupValue95% CI
CFZ5330.1778± 0.13077
Placebo0.1577± 0.17243
week 25
GroupValue95% CI
CFZ533191.1278± 69.67597
Placebo0.1163± 0.18298
Plasma CFZ533 Concentration at Steady State Conditions (Week 17) Secondary · week 17
GroupValue95% CI
CFZ533120± 40.5

Adverse events — posted to ClinicalTrials.gov

Time frame: up to week 49. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CFZ533 10 mg/kg IV Infusion
Serious: 7/22 (32%)
Deaths: 0/22
Placebo IV Infusion
Serious: 4/22 (18%)
Deaths: 2/22

Serious adverse events (13 terms)

ReactionSystemCFZ533 10 mg/kg IV InfusionPlacebo IV Infusion
InfluenzaInfections and infestations
Myasthenia gravisNervous system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Myocardial ischaemiaCardiac disorders
GlaucomaEye disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
PyrexiaGeneral disorders
Hepatitis toxicHepatobiliary disorders
PneumoniaInfections and infestations
Brachial plexopathyNervous system disorders
Myasthenia gravis crisisNervous system disorders
Radial nerve palsyNervous system disorders
Other adverse events (124 terms — click to expand)

ReactionSystemCFZ533 10 mg/kg IV InfusionPlacebo IV Infusion
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
NauseaGastrointestinal disorders
NasopharyngitisInfections and infestations
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
AstheniaGeneral disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
CystitisInfections and infestations
Herpes zosterInfections and infestations
PneumoniaInfections and infestations
Respiratory tract infection viralInfections and infestations
Free haemoglobin presentInvestigations
Muscle spasmsMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Myasthenia gravisNervous system disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders
LymphocytosisBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
NeutrophiliaBlood and lymphatic system disorders
Angina pectorisCardiac disorders
Atrial fibrillationCardiac disorders
PalpitationsCardiac disorders
Von Willebrand's diseaseCongenital, familial and genetic disorders
CataractEye disorders
Vision blurredEye disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Dental cariesGastrointestinal disorders
Food poisoningGastrointestinal disorders
GastroduodenitisGastrointestinal disorders
Gingival bleedingGastrointestinal disorders
Pancreatitis chronicGastrointestinal disorders
ChillsGeneral disorders
DiscomfortGeneral disorders

Most-reported serious reactions: Influenza, Myasthenia gravis, Febrile neutropenia, Myocardial ischaemia, Glaucoma, Abdominal pain upper, Constipation, Pyrexia.

Data from ClinicalTrials.gov NCT02565576 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate safety, tolerability, pharmacokinetics/pharmacodynamics and efficacy of CFZ533 as an add-on therapy to standard of care in patients with moderate to severe myasthenia gravis (MG).

Publications & conference data

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

  1. Outcome Measures in Clinical Trials of Patients With Myasthenia Gravis.
    Thomsen JLS, Andersen H. · · 2020 · cited 47× · PMID 33424747 · DOI 10.3389/fneur.2020.596382
  2. Advances in autoimmune myasthenia gravis management.
    Wang S, Breskovska I, Gandhy S, Punga AR, et al · · 2018 · cited 46× · PMID 29932785 · DOI 10.1080/14737175.2018.1491310
  3. Advances and challenges in the treatment of myasthenia gravis.
    Schneider-Gold C, Gilhus NE. · · 2021 · cited 40× · PMID 34987614 · DOI 10.1177/17562864211065406
  4. 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
  5. New Pathways and Therapeutic Targets in Autoimmune Myasthenia Gravis.
    Behin A, Le Panse R. · · 2018 · cited 39× · PMID 30010142 · DOI 10.3233/jnd-170294
  6. Novel Immunotherapies for Myasthenia Gravis.
    Nair SS, Jacob S. · · 2023 · cited 38× · PMID 37038596 · DOI 10.2147/itt.s377056
  7. Immunotherapies in MuSK-positive Myasthenia Gravis; an IgG4 antibody-mediated disease.
    Vakrakou AG, Karachaliou E, Chroni E, Zouvelou V, et al · · 2023 · cited 33× · PMID 37564637 · DOI 10.3389/fimmu.2023.1212757
  8. From Traditional to Targeted Immunotherapy in Myasthenia Gravis: Prospects for Research.
    Mantegazza R, Antozzi C. · · 2020 · cited 30× · PMID 32982957 · DOI 10.3389/fneur.2020.00981

Verify or expand the search:

Other trials of CFZ533

Trials testing the same drug.

Other recruiting trials for Myasthenia Gravis, Generalized

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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Data sources for this page

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/NCT02565576.

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