Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis
Condition: Myasthenia Gravis, Generalized
MeSH terms: Myasthenia Gravis; Muscle Weakness
Intervention: Placebo; CFZ533
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: CFZ533, Myasthenia Gravis

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).
    

Eligibility criteria:

        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).