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

Novartis Pharmaceuticals1 site in 1 country44 target enrollmentSeptember 29, 2015

ConditionsMyasthenia Gravis, Generalized

InterventionsPlacebo CFZ533

DrugsPlacebo CFZ533

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Myasthenia Gravis, Generalized
Sponsor: Novartis Pharmaceuticals
Enrollment: 44
Locations: 1
Primary Endpoint: Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type.
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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).

Registry

clinicaltrials.gov

Start Date

September 29, 2015

End Date

December 19, 2017

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility 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 \< 15 no more than 4 points may be derived from items 1 or 2 (ocular motility disturbance and ptosis).
•Documented history of acetylcholine receptor (AChR) or Muscle Specific Kinase (MuSK) antibody positive.
•Only one immunosuppressant or immunomodulatory drug at a stable dose is allowed during the study (i) azathioprine and mycophenolate mofetil must be stable for at least 4 months prior to randomization (ii) cyclosporine must be stable for at least 3 months prior to randomization.
•If the patient is on oral corticosteroids, methotrexate or tacrolimus at screening, the dose must be stable for at least 1 month prior to randomization.
•If the patient is on cholinesterase inhibitors at screening, the dose must be stable for at least 2 weeks prior to randomization.
•Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, may be included in the study if they are using highly effective methods of contraception during the study and for 12 weeks after study treatment.

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 thehalf-life, whichever is longer.

Arms & Interventions

CFZ533

Intervention: Placebo

CFZ533

Intervention: CFZ533

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: 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).

Secondary Outcomes

Number of Patients Who Discontinued Due to Inefficacy or Worsening(week 49)
Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type.(From baseline to week 49)
Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score(at week 49)
Proportion of Patients Intolerant to Steroid Taper(week 49)
Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL)(week 25)
Mean Changes From Baseline in the QMG Score at Week 49(week 49)
Mean Change From Baseline in the Myasthenia Gravis Quality of Life (MG QOL-15)(week 25)
Free CD40 on B Cells(week 1, week 25)
Total Soluble CD40 (sCD40) in Plasma(week1, week 25)
Plasma CFZ533 Concentration at Steady State Conditions (Week 17)(week 17)