Clinical trial NCT02565576: Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis, Generalized
Keywords: CFZ533, Myasthenia Gravis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-10-01
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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).

Primary outcomes:
measure: Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type.
timeFrame: week 25
Secondary outcomes:
measure: Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type.
timeFrame: From baseline to week 49
measure: Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score
timeFrame: at week 49
measure: Proportion of Patients Intolerant to Steroid Taper
timeFrame: week 49
measure: Number of Patients Who Discontinued Due to Inefficacy or Worsening
timeFrame: week 49
measure: Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL)
timeFrame: week 25
measure: Mean Changes From Baseline in the QMG Score at Week 49
timeFrame: week 49
measure: Mean Change From Baseline in the Myasthenia Gravis Quality of Life (MG QOL-15)
timeFrame: week 25
measure: Free CD40 on B Cells
timeFrame: week 1, week 25
measure: Total Soluble CD40 (sCD40) in Plasma
timeFrame: week1, week 25
measure: Plasma CFZ533 Concentration at Steady State Conditions (Week 17)
timeFrame: week 17
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Aarhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Halle/S
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Samara
country: Russian Federation
facility: Novartis Investigative Site
state: Samara Region
city: Barnaul
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Novosibirsk
country: Russian Federation
facility: Novartis Investigative Site
city: S-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
References: