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 |
Myasthenia gravis is an autoimmune disease that causes weakness in your muscles; it is caused by a communication problem between nerves and muscles.
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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 | 21.1 |
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 |
Evaluate the long-term safety and tolerability of rozanolixizumab in study participants with generalized myasthenia gravis (MG)
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E.2.2 | Secondary objectives of the trial |
Evaluate the long-term efficacy of rozanolixizumab in study participants with generalized myasthenia gravis (MG)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participant must be ≥18 years of age at the time of signing the informed consent - Participant was eligible for MG0003 [NCT03971422] at the time of enrollment into MG0003 and the participant either completed the Observation Period of MG0003 or required rescue therapy during the Observation Period of MG0003 - Body weight >35 kg at Visit 1 - Study participants may be male or female - A male study participant must agree to use contraception - Female study participants of childbearing potential must agree to use a highly effective method of birth control - A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance |
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E.4 | Principal exclusion criteria |
- Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, if applicable, chest X-rays (posterior anterior and lateral), and TB testing by a positive (not indeterminate) QuantiFERON®-TB Gold test - Participant has received a live vaccination within 8 weeks prior to the Baseline visit; or intends to have a live vaccination during the course of the study or within 8 weeks following the final dose of study medication - Study participant has experienced hypersensitivity reaction after exposure to other antineonatal Fc receptor (FcRn) drugs - Study participant with severe (defined as Grade 3 on the myasthenia gravis-activates of daily living (MG-ADL) scale) weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis - Participant has absolute neutrophil count <1500 cells/mm3 - Participant has any laboratory abnormality that, in the opinion of the Investigator, is clinically significant, has not resolved at randomization, and could jeopardize or compromise the study participant’s ability to participate in this study - Participant has 12-lead electrocardiogram (ECG) with findings considered to be clinically significant upon medical review. The clinical significance of the findings needs to be assessed by the Investigator to determine eligibility, and any queries regarding continuation of the study participant must be addressed with the Medical Monitor - Study participant has renal impairment, defined as serum creatinine level of ≥1.4 mg/dL for females and ≥1.5mg/dL for males - Study participant has >2x upper limit of normal (ULN) of any of the following at Visit 1: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). If study participant has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%). For randomized study participants with a baseline result >ULN for ALT, AST, ALP, or total bilirubin but <1.5xULN, a baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic Case Report form (eCRF). Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit (>2xULN) may be repeated once for confirmation - Study participant has positive human immunodeficiency virus antibody test - Study participant met any mandatory withdrawal or mandatory study drug discontinuation criteria MG0003 [NCT03971422] or discontinued study medication in MG0003, with the exception of discontinuation due to a need for rescue treatment - Study participant is not considered capable of adhering to the protocol visit schedule, or medication intake according to the judgment of the Investigator - Study participant has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or had suicidal ideation since the last visit in MG0003 as indicated by a positive response (Yes) to either Question 4 or Question 5 of the ColumbiaSuicide Severity Rating Scale (C-SSRS) at Screening |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Percentage of participants with treatment-emergent adverse events (TEAEs) 2. Percentage of participants with treatment-emergent adverse events (TEAEs) leading to permanent withdrawal of study medication
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.+2.: From Baseline until Final Visit (up to Week 60)
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E.5.2 | Secondary end point(s) |
1. Change from Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at each scheduled assessment during Treatment and Observation Periods 2. Change from Baseline in Myasthenia Gravis (MG)-Composite score at each scheduled assessment during Treatment and Observation Periods 3. Change from Baseline in Quantitative Myasthenia Gravis (QMG) score at each scheduled assessment during Treatment and Observation Periods 4. Percentage of participants using rescue medication (intravenous infusion of immunoglobulin G (IVIg) or plasma exchange (PEX)) during the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.-4.: From Baseline at each scheduled assessment during Treatment and Observation Periods (up to Week 60)
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Immunogenicity
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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) | 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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | Information not present in EudraCT |
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 | 55 |
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 |
Belgium |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Italy |
Poland |
Russian Federation |
Spain |
United Kingdom |
United States |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 14 |
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 | 1 |