Generalized AChR-antibody positive Myasthenia Gravis MedDRA version: 21.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: rituximab
Product Code: [rituximab]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rituximab
CAS Number: 174722-31-7
Current Sponsor code: rituximab
Othe
Sponsors
FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects = 18 years old. 2. Written informed consent and European Union Data Privacy Directive obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. 3. Diagnosis of MG defined as: a. Positive serologic test for anti-AChR or anti-MuSK antibody titers as confirmed at screening (one retest allowed), and b. At least one of the following: • History of abnormal neuromuscular transmission test results demonstrated by single-fiber electromyography or repetitive nerve stimulation; or • History of positive anticholinesterase test (eg, edrophonium chloride test); or • Patient demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician; or • Clinical syndrome consistent with a diagnosis of MG, and not otherwise explained by another condition. 4. MGFA Clinical Classification Class II, III, or IV at the time of screening and randomization. 5. MG-ADL score of 5 or greater at screening and at randomization with > 50% of this score attributed to non-ocular items. 6. QMG score of 11 or greater at screening and at randomization. 7. Subjects must be on corticosteroids only, with no dose increase within 4 weeks prior to randomization and at least 20 mg prednisone per day (or equivalent dose on alternate day regimen) 8. Willing and able to comply with the protocol, complete study assessments, and return for follow-up visits. 9. Females of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective contraception method (Table 1) from the time of screening and for 6 months after the final dose of IP. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (defined as 12 months with no menses without an alternative medical cause). 10. Non-sterilized males who are sexually active with a female partner of childbearing potential must use a condom from Day 1 for the duration of the study and for 3 months after the last dose of IP. Because male condom is not a highly effective contraception method, it is strongly recommended that female partners of a male study subject also use a highly effective method of contraception throughout this period (Table 1). 11. Vital signs, electrocardiogram (ECG), and laboratory parameters within the normal ranges at screening, or, if outside normal ranges, deemed not clinically significant by the Investigator. 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Any condition that, in the opinion of the Investigator, would place the patient at unacceptable risk of complications, interfere with evaluation of the IP, or confound the interpretation of patient safety or study results. 2. Lactating or pregnant females, or females who intend to become pregnant anytime from signing the informed consent form (ICF) throughout the RCP plus 6 months following last dose of IP. 3. History of drug or alcohol abuse within 480 mg/day or unstable dose in the 2 weeks prior to Day 1 13. Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 half-lives of the investigational treatment, whichever is longer, prior to Day 1. 14. Receipt of a live attenuated vaccine within 4 weeks prior to randomization. Administration of inactivated (killed) vaccines is acceptable. 15. History of severe allergic or anaphylactic reactions to biologic agents or known allergy to any component of the IP formulation. 16. History of recurrent significant infections (eg, requiring hospitalization or IV antibiotics). 17. Within 2 weeks prior to the screening visit: clinically significant active infection requiring antimicrobial medication but allowing chronic nail infections.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether rituximab can reduce MG-related functional impairment.;Secondary Objective: 1. To evaluate the effect of rituximab on corticosteroid usage. 2. To evaluate the effect of rituximab on MG-related disability. 3. To evaluate whether rituximab can improve MG-related quality of life. 4. To evaluate the safety and tolerability of rituximab in MG. 5. To evaluate if rituximab reduces MG exacerbations;Primary end point(s): Change from baseline in Quantitative Myasthenia Gravis Score (QMG) at week 12 (3 months) of the RCP;Timepoint(s) of evaluation of this end point: 3 MONTHS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in corticosteroid dosage from week 12 to the end of the RCP. 2. Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 12. 3. Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score at the end of RCP. 4. Change from baseline in Quantitative Myasthenia Gravis Score (QMG) score at the end of RCP. 5. Proportion of subjects with both (1) = 3-point improvement in MG-ADL at end of the RCP (2) no use of rescue therapy during RCP. 6. Change from baseline in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score at the week 12 and at the end of the RCP 7. Proportion of patients achieving the status of minimal-manifestation or better at week 12 and the end of the RCP 8. Proportion of patients requiring rescue therapy during the RCP.;Timepoint(s) of evaluation of this end point: 12 MONTHS | — |
Countries
Italy
Contacts
Public ContactDirezione Scientifica
Fondazione Policlinico Universitario A. Gemelli IRCCS
Outcome results
None listed