E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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E.1.1.1 | Medical condition in easily understood language |
Myasthenia Gravis is an autoimmune chronic neuromuscular disorder characterised by muscle weakness and fatigability that can be extreme. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028417 |
E.1.2 | Term | Myasthenia gravis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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).
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E.2.2 | Secondary objectives of the trial |
•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 MGQOL15 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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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, druginduced 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Change from baseline in Quantitative Myasthenia Gravis (QMG) physician assessment compared to the placebo group.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
24 weeks after the first injection. |
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E.5.2 | 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. |
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E.5.2.1 | 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.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |