Phase 2
N=44
Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis
Myasthenia Gravis, Generalized
Bottom Line
View on ClinicalTrials.gov: NCT02565576 ↗Enrolled (actual)
44
Serious AEs
25.0%
Results posted
Jul 2019
Primary outcome: Primary: Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type. — -4.07; -2.93 score
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); CFZ533 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline in the Quantitative Myastenia Gravis (QMG) Score at Week 25. Posterior Median Was Used as Measure Type. |
-4.07; -2.93 | — |
| SECONDARY Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type. |
-8.00; -5.62 | — |
| SECONDARY Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score |
10; 9; 2; 2 | — |
| SECONDARY Proportion of Patients Intolerant to Steroid Taper |
NA; NA | — |
| SECONDARY Number of Patients Who Discontinued Due to Inefficacy or Worsening |
0; 0 | — |
| SECONDARY Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) |
-2.6; -1.1 | — |
| SECONDARY Mean Changes From Baseline in the QMG Score at Week 49 |
-2.9; -2.6 | — |
| SECONDARY Mean Change From Baseline in the Myasthenia Gravis Quality of Life (MG QOL-15) |
-9.7; -6.7 | — |
| SECONDARY Free CD40 on B Cells |
34242.9; 31025.9; 5259.1; 24908.3 | — |
| SECONDARY Total Soluble CD40 (sCD40) in Plasma |
0.1778; 0.1577; 191.1278; 0.1163 | — |
| SECONDARY Plasma CFZ533 Concentration at Steady State Conditions (Week 17) |
120 | — |
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
- 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.
- Live vaccines within 4 weeks of study drug infusion.
- 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).
Data sourced from ClinicalTrials.gov (NCT02565576). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.