Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02565576
Recruitment Status : Completed
First Posted : October 1, 2015
Results First Posted : July 25, 2019
Last Update Posted : July 25, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 23, 2015
First Posted Date  ICMJE October 1, 2015
Results First Submitted Date  ICMJE December 12, 2018
Results First Posted Date  ICMJE July 25, 2019
Last Update Posted Date July 25, 2019
Actual Study Start Date  ICMJE September 29, 2015
Actual Primary Completion Date July 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 29, 2015)
Mean change from baseline in the Quantitative Myastenia Gravis (QMG) score [ Time Frame: At week 25 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
  • Mean Changes From Baseline in the Myasthenia Gravis Composite (MGC) Score. Posterior Median Was Used as Measure Type. [ Time Frame: From baseline to week 49 ]
    The Myasthenia Gravis Composite (MGC) score is another key efficacy outcome measure, ranging from 0 to 50. It is reliable and demonstrates concurrent and longitudinal construct validity in the MG practice care setting (Burns et al 2010). The MGC scale covers 10 important functional domains most frequently involved in patients with MG. The proportion of bulbar and respiratory items reflect the clinical importance of these domains in the disease, and are appropriately weighted. The assessment of each of the 10 test items provides immediate insight into the status of that particular functional domain. A decrease in this score shows an improvement.
  • Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score [ Time Frame: at week 49 ]
    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).
  • Proportion of Patients Intolerant to Steroid Taper [ Time Frame: week 49 ]
  • Number of Patients Who Discontinued Due to Inefficacy or Worsening [ Time Frame: week 49 ]
  • Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) [ Time Frame: week 25 ]
    The MG-ADL is an 8-item survey to assess functional performance of daily activities that are sometimes impaired by MG e.g. talking, breathing, swallowing etc. (Muppidi et al 2011). The higher score on MG-ADL scale (0-24 points) indicates worse functional performance of daily activities.
  • Mean Changes From Baseline in the QMG Score at Week 49 [ Time Frame: week 49 ]
    QMG (quantitative myasthenia gravis) 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). A decrease in the QMG score indicated an improvement. Results given as a change in the score as compared from baseline
  • Mean Change From Baseline in the Myasthenia Gravis Quality of Life (MG QOL-15) [ Time Frame: week 25 ]
    The MG-QOL15 is a 15-item survey, completed by MG patients and it is designed to assess some aspects of quality of life (QoL) related to MG (Burns et al 2011) e.g. assesment of mood, eating, speaking, driving a car etc.. The higher score on MG-QOL15 scale (0-60 points) indicates worse QoL.
  • Free CD40 on B Cells [ Time Frame: week 1, week 25 ]
    CD40 receptor occupancy by CFZ533 in peripheral blood was assessed by flow cytometry analysis, measuring free or total CD40 receptors on whole blood B cells. Free CD40 on CD19-positive B cells, using PE-conjugated CFZ533 whose binding was prevented by bound, unconjugated CFZ533 (drug bound to CD40 on peripheral blood B cells). The more CD40 was occupied by unlabeled CFZ533, the less binding of labeled CFZ533, manifest as a lower mean fluorescence intensity (MFI) of CD40 on B cells. MFI from free CD40 on B cells was converted into Molecules of Equivalent Soluble Fluorochrome (MESF) using PE-MESF beads.
  • Total Soluble CD40 (sCD40) in Plasma [ Time Frame: week1, week 25 ]
    PD
  • Plasma CFZ533 Concentration at Steady State Conditions (Week 17) [ Time Frame: week 17 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2015)
  • Mean changes from baseline in the MGC score [ Time Frame: From baseline to week 49 ]
  • Proportion of Patients With Improvement or Worsening by ≥ 3 Points in the QMG Score [ Time Frame: From baseline to week 49 ]
  • Proportion of Patients Intolerant to Steroid Taper [ Time Frame: from week 13 to week 49 ]
  • Proportion of patients who discontinued due to inefficacy or worsening [ Time Frame: from baseline to week 49 ]
  • Mean Change From Baseline in the Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) [ Time Frame: From baseline to week 24 ]
  • Mean changes from baseline in the QMG score [ Time Frame: From baseline to week 49 ]
  • Mean change from baseline in the Myasthenia Gravis Quality of Life (MG QOL-15) [ Time Frame: From baseline to week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety,Tolerability,Pharmacokinetics and Efficacy of CFZ533 in Moderate to Severe Myasthenia Gravis
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Myasthenia Gravis, Generalized
Intervention  ICMJE
  • Drug: Placebo
  • Drug: CFZ533
Study Arms  ICMJE
  • Active Comparator: CFZ533
    CFZ533
    Interventions:
    • Drug: Placebo
    • Drug: CFZ533
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 29, 2015)
44
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 19, 2017
Actual Primary Completion Date July 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Denmark,   Germany,   Russian Federation,   Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02565576
Other Study ID Numbers  ICMJE CCFZ533X2204
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP