Myasthenia Gravis MedDRA version: 20.0 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Grifols Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female ages 18 to 85 years 2. Anti-AChR antibody positive 3. Confirmed diagnosis of generalized MG historically meeting the clinical criteria for diagnosis of MG defined by the MGFA classification of Class II, III, IV, or V historically (Appendix 2). 4. At Screening, subjects may have symptoms controlled by CS (for example, only ocular [Class I] symptoms may be evident or there may be no symptoms) or be MGFA Class II-IVa inclusive (Class IVb and Class V excluded). Note: Subjects who only have a history of ocular MG may not enroll. 5. On systemic CS for a minimum period of at least three months and on a stable CS dose of =15 mg/day and =60 mg/day (prednisone equivalent) for the month prior to Screening. Individuals on alternate day CS dosing will be judged to be on a daily dose equivalent to half their alternate day dose (i.e., 40 mg/every other day = 20 mg/day). 6. The investigator feels that tapering the CS dose is currently appropriate (to be commenced as prescribed during this protocol) 7. At least one previous completed attempt to taper CS in order to minimize CS dose 8. Subjects must be willing and able to provide written informed consent 9. Subjects must be willing to comply with all aspects of the clinical trial protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Any dose change in concomitant immunosuppressant therapy, other than CS, in the prior six months 2. Any change in CS dose or acetylcholinesterase inhibitor (e.g., pyridostigmine) dose in the one month prior to Screening 3. A three-point change in QMG score, increased or decreased, between the Screening/Week -3 (Visit 0) and Baseline (Week 0 [Visit 1]) 4. Any episode of MC in the one month prior to Screening or (at any time in the past) MC or hospitalization for MG exacerbation associated with a previous CS taper attempt 5. Evidence of malignancy within the past 5 years (non-melanoma skin cancer, carcinoma in situ of cervix is allowed) or thymoma potentially requiring surgical intervention during the course of the trial (intent to perform thymectomy) 6. Thymectomy within the preceding six months prior to Screening 7. Rituximab, belimumab, eculizumab or any monoclonal antibody used for immunomodulation within the past 12 months prior to Screening 8. History of non-response to IVIg when used in maintenance therapy of the subject’s MG, as judged by the investigator 9. Have received immune globulin treatment given by IV, subcutaneous, or intramuscular route within the last 3 months prior to Screening 10. Received plasma exchange (PLEX) performed within the last 3 months prior to Screening 11. Inadequate venous access 12. History of anaphylactic reactions or severe reactions to any blood-derived product 13. History of intolerance to any component of the IPs 14. Documented diagnosis of thrombotic complications to polyclonal IVIg therapy in the past 15. History of recent (within the last year) myocardial infarction or stroke 16. Uncontrolled congestive heart failure; embolism; or historically documented (within the last year) electrocardiogram (ECG) changes indicative of myocardial ischemia or atrial fibrillation 17. Current known hyperviscosity or hypercoagulable state 18. Currently receiving anti-coagulation therapy (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [e.g., dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and apixaban targeting Factor Xa], parenteral anticoagulants [e.g., fondaparinux]). Note that oral anti-platelet agents are allowed (e.g., aspirin, clopidogrel, ticlodipine) 19. History of chronic alcoholism or illicit drug abuse (addiction) in the 12 months preceding the Screening/Week -3 (Visit 0) 20. Active psychiatric illness that interferes with compliance or communication with health care personnel 21. Females of child-bearing potential who are pregnant, have a positive serum pregnancy test (human chorionic gonadotropin [HCG]-based assay), breastfeeding, or are unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, condom or occlusive cap with spermicidal foam/ gel/film/cream/suppository, male sterilization, or true abstinence*) throughout the study. * True abstinence: When this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception.) 22. Currently receiving, or having received within 1 month prior to the Screening/Week -3 (Visit 0), any investigational medicinal product or device. In the case of an investigational
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objectives of this study are to evaluate the efficacy of IGIV-C as compared to Placebo from baseline through Week 39 in the following: * Percent reduction in daily CS (prednisone or equivalent) dose from Baseline to Week 39 (Visit 14) * Time to first episode of MG worsening, as defined in Section 3.3.3 “Definition and Management of MG Worsening”, from Baseline/Week 0 through Week 39 (Visit 1 through Visit 14);Primary end point(s): The primary efficacy endpoint will be the percent of subjects in each arm achieving a 50% or greater reduction in CS dose (prednisone or equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1). ;Timepoint(s) of evaluation of this end point: at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1). ;Main Objective: The primary objective of this study is to evaluate the efficacy of IV infusions of IGIV-C as compared to Placebo in reducing the maintenance dosage of corticosteroids in corticosteroid (CS)-dependent subjects with MG when given as an initial loading dose (2 g/kg) followed by 12 maintenance doses (1 g/kg) every 3 weeks through Week 36 by assessing the percent of subjects achieving a 50% or greater reduction in CS dose(prednisone or equivalent) at Week 39 (Visit 14) from Baseline/Week 0 (Visit 1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percent reduction in daily CS (prednisone or equivalent) dose from Baseline/Week 0 to Week 39 (Visit 14) 2. Time to first episode of MG worsening, as defined in Section 3.3.3 “Definition and Management of MG Worsening”, from Week 0 through Week 39 (Visit 1 through Visit 14);Timepoint(s) of evaluation of this end point: 1. Throughout the study at each visit until the Week 39 including. 2. Throughout the study at each visit until the Week 39 including. | — |
Countries
Belgium, Canada, Czech Republic, Estonia, France, Germany, Hungary, Lithuania, Poland, United States
Contacts
Public ContactRhonda Griffin-Director,ClinDev
Grifols Therapeutics Inc.
Outcome results
None listed