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

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).

Inclusion Criteria:

1. Diagnosis of MG class IIa to IVa inclusive (Myasthenia Gravis Foundation of America Clinical Classification).
2. 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).
3. Documented history of acetylcholine receptor (AChR) or Muscle Specific Kinase (MuSK) antibody positive.
4. 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.
5. 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.
6. If the patient is on cholinesterase inhibitors at screening, the dose must be stable for at least 2 weeks prior to randomization.
7. 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:

1. MGFA grade I, IVb, or V disease.

2. Documented presence of unresected thymoma.

3. Patients having undergone thymectomy or thymo thymectomy (resection of thymoma) within 6 months of screening.

4. Patients having received any of the following treatments prior to randomization:

   1. IVIg or plasma exchange within 8 weeks;
   2. oral or IV cyclosphosphamide treatment within 3 months;
   3. IV corticosteroid bolus (dose higher than 1 mg/kg) within 3 months;
   4. belimumab within 6 months. For patients who received belimumab earlier, B cell count should be within normal range;
   5. rituximab within 12 months. For patients who received rituximab earlier, B cell count should be within normal range;
   6. any other biologic or an investigational drug within 1 month or five times thehalf-life, whichever is longer.
   7. Live vaccines within 4 weeks of study drug infusion.

5. Patients who are at significant risk for TE as judged by the investigator or have any one of the following:

   1. History of either thrombosis or 3 or more spontaneous abortions with or without the presence of anti-cardiolipin autoantibodies;
   2. Presence of prolonged partial thromboplastin time (PTT).