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 ravulizzumab 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 the quality of life measures.
To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on other efficacy endpoint |
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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 a 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 | 32 |
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 |
Denmark |
France |
Germany |
Italy |
Netherlands |
Spain |
Switzerland |
Czechia |
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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 | 2 |
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 | 2 |
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 |