Acquired myasthenia gravis (MG) is an autoimmune disease that leads to fluctuating muscle weakness and fatigue. In the most common cases, muscle weakness is caused by circulating antibodies that bind to acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine. MedDRA version: 18.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Code: CFZ533
Pharmaceutical Form: Powder for solution for injection/infusion
Other descriptive name: CFZ533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentr
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of MG class IIa to IVa inclusive (Myasthenia Gravis Foundation of America Clinical Classification). • Quantitative Myasthenia Gravis (QMG) score of 10 or greater. If the QMG score is =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • MGFA grade I, IVb, or V disease. • Documented presence of unresected thymoma. • Patients having undergone thymectomy or thymo thymectomy (resection of thymoma) within 6 months of screening. • Patients having received any of the following treatments prior to randomization: IVIg or plasma exchange within 8 weeks oral or IV cyclosphosphamide treatment within 3 months; IV corticosteroid bolus (dose higher than 1 mg/kg) within 3 months; belimumab within 6 months. For patients who received belimumab earlier, B cell count should be within normal range; rituximab within 12 months. For patients who received rituximab earlier, B cell count should be within normal range; any other biologic or an investigational drug within 1 month or five times the half-life, whichever is longer. • Live vaccines within 4 weeks prior to randomization. • Patients who are at significant risk for TE as judged by the investigator or have any one of the following: - History of either thrombosis or 3 or more spontaneous abortions with or - without the presence of anti-cardiolipin autoantibodies; • Presence of prolonged partial thromboplastin time (PTT).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the safety and tolerability of CFZ533 as an add-on therapy to standard of care in moderate to severe MG patients. • To evaluate the efficacy of IV CFZ533 as an add-on therapy to standard of care in patients with moderate to severe MG after 24 weeks of treatment.;Secondary Objective: • To evaluate the efficacy of CFZ533 throughout the 24 weeks treatment period and the decay in efficacy throughout the 24 weeks follow-up period. • To evaluate changes in patient’s quality of life (QOL) throughout 24 weeks the treatment period. • To evaluate the pharmacokinetics of CFZ533 • To evaluate the pharmacodynamics of CFZ533 • To assess immunogenicity of CFZ533;Primary end point(s): • Mean change from baseline in the QMG Score for Disease Severity after 24 weeks of treatment (primary endpoint). ;Timepoint(s) of evaluation of this end point: After 24 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Mean Change from baseline in QMG Score and MGC Score.. • Proportion of patients with improvement by = 3 points in QMG score. • Proportion of patients with worsening by = 3 points in QMG score. • Proportion of patients intolerant to steroid taper. • Proportion of patients who discontinued due to inefficacy or worsening. • Mean change from baseline in the MG-ADL and MG QOL-15. • Free CFZ533 in plasma • Free CD40 on B cells, total CD40 on B cells and total soluble CD40 in plasma • Quantitative analysis of anti-CFZ533 antibodies in plasma ;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Canada, Denmark, Germany, Russian Federation, Taiwan
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed