E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Myasthenia Gravis |
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E.1.1.1 | Medical condition in easily understood language |
Generalized Myasthenia Gravis |
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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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10071942 |
E.1.2 | Term | Myasthenia gravis and related conditions |
E.1.2 | System Organ Class | 100000004859 |
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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 ravulizumab compared with placebo in the treatment of gMG based on the improvement in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) profile. |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on the improvement in the Quantitative Myasthenia Gravis (QMG) total score. • To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on the improvement in quality of life measures. • To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on other efficacy endpoints. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female patients ≥ 18 years of age • Diagnosed with MG at least 6 months (180 days) prior to the date of the Screening Visit as confirmed by protocol-specific criteria • Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening • MG-ADL profile must be ≥ 6 at screening and randomization (Day 1) • Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug to reduce the risk of meningococcal infection (N meningitidis). • Body weight ≥ 40 kg at the time of screening • Patients of childbearing potential and patients with partners of childbearing potential must follow protocol-specified contraception guidance for avoiding pregnancy while on treatment and for 8 months after last dose of study drug
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E.4 | Principal exclusion criteria |
Medical Conditions: • Any active or untreated thymoma. History of thymic carcinoma or thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before Screening • History of thymectomy, thymomectomy, or any thymic surgery within the 12 months prior to screening • History of N meningitidis infection • Human immunodeficiency virus (HIV) infection • History of hospitalization for ≥ 24 hours, for any reason, within the 4 weeks (28 days) prior to screening • Females who plan to become pregnant during the study, or are currently pregnant or breastfeeding, or who have a positive pregnancy test result at screening or on Day 1 • History of unexplained infections • Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug administration on Day 1 • Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study drug administration on Day 1
Prior/Concomitant Therapy •Use of the following within the time period specified below: - IVIg within the 4 weeks (28 days) prior to randomization (Day 1) - Use of PE within the 4 weeks (28 days) prior to randomization (Day 1) - Use of rituximab within the 6 months (180 days) prior to screening • Patients who have received previous treatment with complement-inhibitors (eg, eculizumab)
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline in MG-ADL total score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At Week 26 of the Randomized-Controlled Period. |
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E.5.2 | Secondary end point(s) |
• Change from Baseline in QMG total score • Change from Baseline in the Revised 15-Component Myasthenia Gravis Quality of Life (MG-QoL15r) score • Change from Baseline in Neuro-QoL Fatigue score • Improvement from Baseline of at least 3 points in the MG-ADL total score • Improvement from Baseline of at least 5 points in the QMG total score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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) | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Israel |
Japan |
Korea, Republic of |
United States |
Austria |
Czechia |
Denmark |
France |
Germany |
Italy |
Portugal |
Netherlands |
Spain |
Switzerland |
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E.8.7 | Trial has a data monitoring committee | No |
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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LVLS in the study or last scheduled procedure shown in the Schedule of Activities for the last patient in the study globally |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |