Neoplasms

Nervous System Diseases

Immune System Diseases

All Conditions

Musculoskeletal Diseases

Symptoms and General Pathology

Rare Diseases

Myasthenia Gravis

Muscle Weakness

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

Placebo

CFZ533

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).

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

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Preliminarily Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of CFZ533 in Patients With Moderate to Severe Myasthenia Gravis

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).

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 domain. A decrease in this score shows an improvement.

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.

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 change in the score as compared from baseline

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.

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-MESF beads.

Novartis Pharmaceuticals

CFZ533 10 mg/kg IV Infusion

Placebo IV Infusion

Total

Age, Continuous

Sex: Female, Male

caucasian

Asian (Chinese)

other

Race/Ethnicity, Customized

Study Director

Primary analysis was performed on the PD analysis set. Changes from baseline in QMG scores at Week 25 were analyzed using a Bayesian model. The model investigated effects for treatment (CFZ533 or placebo) and baseline QMG score. A difference of 3 points on the mean change in QMG score between CFZ533 and placebo was deemed a clinical meaningful effect.

pharmacodynamic (PD) analysis set, participants with non-detectable AChR or MuSK autoantibodies were excluded from the PD analysis set.

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

Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type.

improvement by ≥ 3 points in the QMG score

worsening by ≥ 3 points in the QMG score

PD analysis set, participants with measure

Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score

this data was not collected. No analysis could be performed for this outcome measure.

Proportion of Patients Intolerant to Steroid Taper

Number of Patients Who Discontinued Due to Inefficacy or Worsening

Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL)

Spots Global Cancer Trial Database for cfz533, myasthenia gravis