Myasthenia Gravis (MG) is a chronic neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. The underlying defect is a decrease in the number of available acetylcholine receptors (AChRs) at neuromuscular junctions due to an antibody-mediated autoimmune attack. MedDRA version: 19.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: CV-MG01
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Not applicable
Current Sponsor code: RhCA611-001-CRM197
Other descriptive name: T-peptide-CRM197 conjugate
Conc
Sponsors
CuraVac Europe SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: [1] Male or female Patient, with generalised myasthenia gravis (Grades 2, 3 and 4a) as per myasthenia gravis foundation of America (MGFA) classification system. [2] Quantitative Myasthenia Gravis (QMG) score of 10 or greater at screening and baseline. [3] Age of minimum 18, at the time of the consent form signature. [4] Patient with documented positive antibodies to AChR in one of the available validated laboratory test. [5] Patient may use corticosteroid treatment initiated for at least 3 months before screening, equivalent to a daily dose of 30mg prednisone as maximum, and stable (+/- 5mg change) at least 1 month before the screening and up to the first injection. . [6] Patient may use one or two immunosuppressive drugs (initiated for a least 6 months) with or without concomitant use of corticosteroid, providing that the dosage has been stable/unchanged for 3 months before the screening and up to the first injection.. [7] Venous access sufficient to allow blood sampling as per the protocol. [8] Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. [9] Have given written informed consent approved by the relevant Ethics Committee (EC) governing the site. 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: [10] MG patients of Grade 5 based on myasthenia gravis foundation of America (MGFA) classification. [11] Patients with history or presence of a primary or recurrent malignant disease including the presence or history of a thymoma. [12] Thymectomy planned during Part A of the study period or performed within 1 year prior to the first dose of study. [13] Any confirmed or suspected immunosuppressive or immunodeficient condition not related to the treatment of MG, including human immunodeficiency virus (HIV) infection, or a family history of congenital or hereditary immunodeficiency. [14] History or evidence of administration of immunoglobulins and/or any blood products within 3 months prior to the first dose of study drug, or a planned administration of immunoglobulins during the first 3 months of the study. [15] History or evidence of rituximab treatment within 6 months prior to first dose of study. [16] History or evidence of plasmapheresis within 3 months prior to the first dose of study, or a planned plasmapheresis during the first 3 months of the study. [17] At high risk for aspiration. [18] Pulmonary: forced vital capacity reduced to less than 70% of predicted capacity. [19] History of severe allergic disease or reactions likely to be exacerbated by any component of the vaccine. [20] History or evidence of Lambert-Eaton myasthenic syndrome, drug-induced myasthenia gravis, hereditary forms of myasthenic syndrome. [21] History of relevant chronic degenerative, psychiatric, or neurological disorder other than MG. [22] Severe hepatic, renal or cardiac insufficiency or uncontrolled hypertension [23] Major congenital defects or serious chronic illness other than MG. [24] Positive pregnancy test or desire to become pregnant during the study. [25] Female patients of child-bearing potential that do not use a reliable and highly effective method of contraception (see Section 7.2 Contraception) at least one month before first injection, during the study and until the end of Part A. [26] Any significant out-of-range Clinical Laboratory results considered as clinically significant and that prevent Subject’s participation into the study according to Investigator’s judgment. [27] Previous completion or withdrawal from this study or study CV-0002. [28] Sponsor employees or Investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted. [29] Any medical condition or concomitant medication that, in the opinion of the Investigator, might interfere with the subject’s participation in the study, poses any added risk for the subject, or confounds the assessment of the subjects.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of 3 subcutaneous injections of CV-MG01 compared to placebo, as measured by a decrease from baseline of the QMG total score at 24 weeks after the first injection. (equivalent to 12 weeks after last treatment injection). ;Secondary Objective: •To further assess the safety and tolerability, •To assess the efficacy by comparing the followings after first injection with the placebo group: - Decrease from baseline of QMG, MG-ADL, MGC and MG-QOL 15 total scores assessed after the end of injection and until the end of study part A, at 18, 24, and 30 weeks, - Decrease in Total Prednisone Dose over a period of 30 weeks, - Decrease in the average Pyridostigmine Daily Dose (mg/Day) over a period of 30 weeks, - Proportion of patients with improvement or worsening by = 3 points in the QMG score at 24 weeks, - Proportion of patients with at least a 2-point reduction in MG-ADL total score from baseline to 24 weeks, - Proportion of patients who discontinued due to inefficacy or worsening of symptoms, - Immunogenic response as measured by plasma levels of antibodies against CV-MG01, - Proportion of patients with a decrease from baseline of serum AChR antibodies of more than 30% at 24 and 30 weeks ;Primary end point(s): Efficacy: Change from baseline in Quantitative Myasthenia Gravis (QMG) physician assessment compared to the placebo group. ;Timepoint(s) of evaluation of this end point: 24 weeks after the first injection. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: [1] change from baseline of MG-ADL Patients self-administered questionnaire, MGC and MG-QOL 15: change from baseline of the total scores. [2] Total Prednisone Dose Area Under the Curve (AUC) over a period of 30 weeks after the first injection and the change from baseline of the total prednisone daily dose measured from 24 to 30 weeks. [3] Average Pyridostigmine Daily Dose (mg/Day) over a period of 30 weeks after the first injection and the change from baseline measured from 24 to 30 weeks. Safety: Treatment emergent adverse events (TEAEs) including local injection site reactions (see Section 8.1 Local Tolerance for specific symptoms) and safety monitoring (physical examinations, vital signs (VS), standard laboratory tests). Immunogenicity: RhCA611-001 Ab (Abs against T-peptide), RhCA67-16 Ab (Antibodies against B-peptide) and AChR serum antibodies.;Timepoint(s) of evaluation of this end point: Safety: all visits Efficacy and Immunogenicity: 24 weeks after the first injection. 18 weeks after the first injection. 30 weeks after the first injection. | — |
Countries
Belgium, Netherlands
Contacts
Public ContactScientific Coordinator
CuraVac Europe SA
Outcome results
None listed