E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Immune System Diseases [C20] |
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 |
To assess the efficacy of ALXN2050 compared with placebo in the treatment of generalized MG (gMG) based on improvement in the Myasthenia Gravis Activities of Daily Living (MG ADL) total score |
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E.2.2 | Secondary objectives of the trial |
- To assess the efficacy of ALXN2050 compared with placebo in the treatment of gMG based on improvement in the Quantitative Myasthenia Gravis (QMG) total score - To assess the efficacy of ALXN2050 compared with placebo in the treatment of gMG based on improvement in quality of life measures - To assess the efficacy of ALXN2050 compared with placebo in the treatment of gMG based on additional endpoints involving the MG ADL total score PK/PD -To characterize the PK/PD of ALXN2050 and to establish the PK/PD relationship in participants with gMG Biomarker: -To assess the effect of factor D inhibition on complement biomarkers Safety: -To characterize the overall safety of ALXN2050 compared with placebo in participants with gMG
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: • Diagnosed with MG at least 3 months (90 days) prior to the date of the Screening Visit. • Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at the Screening Visit. • MG-ADL total score must be ≥ 5 (with at least 50% of the score attributed to non-ocular elements) at the Screening Visit and at randomization (Day 1). • Participants receiving treatment with protocol-specified immunosuppressive therapies, corticosteroids, or acetylcholinesterase inhibitors must have been receiving treatment and on a stable dose prior to the date of the Screening Visit, with no changes to the regimen expected during screening, the PEP, and/or the ETP.
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: • Estimated glomerular filtration rate ≤ 30 milliliters/minute/1.73 squared meters during Screening calculated by Chronic Kidney Disease Epidemiology Collaboration. • History of thymectomy, thymomectomy, or any other thymic surgery within 12 months prior to the Screening Visit. • Any untreated thymic malignancy, carcinoma, or thymoma. Participants with a history of treated thymic malignancy or carcinoma are eligible for enrollment if they meet pre-specified conditions outlined in the protocol. • Clinical features consistent with Clinical Deterioration at the time of the Screening Visit or at any time during the Screening Period prior to randomization (Day 1). • Use of the following within the time periods specified below: a. Intravenous immunoglobulin G or subcutaneous immunoglobulin within the 4 weeks (28 days) prior to the Screening Visit. b. Use of tacrolimus or cyclosporine within the 4 weeks (28 days) prior to the Screening Visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Proportion of participants with a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score reduction of ≥ 2 points in any 4 consecutive weeks during the first 8 weeks and who did not receive rescue therapy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
any 4 consecutive weeks during first 8 weeks |
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E.5.2 | Secondary end point(s) |
2. Change from baseline in QMG total score at Week 8 3. Proportion Of Participants Meeting Prespecified Threshold In The QMG Total Score at Week 8 4. Proportion Of Participants Meeting Prespecified Threshold In The QMG Total Score In Any 4 Consecutive Weeks During The First 8 Weeks And Who Did Not Receive Rescue Therapy 5. Change From Baseline In MG-ADL Total Score At Week 8 6. Proportion Of Participants Meeting Prespecified Threshold In The MG-ADL Total Score In Any 4 Consecutive Weeks During The First 8 Weeks And Who Did Not Receive Rescue Therapy 7. Proportion Of Participants Meeting Prespecified Threshold In The MG-ADL Total Score At Week 8 8. Change From Baseline In Quality Of Life In Neurological Disorders Fatigue Questionnaire (Neuro-QoL) Fatigue Score At Week 8 9. Maximum Peak Plasma Concentration (Cmax) Of ALXN2050 Over Time 10. Pre-dose Concentration (Ctrough) Of ALXN2050 Over Time 11. Absolute Values And Change From Baseline In Plasma Concentration Of Bb Fragment Of Complement Factor B At Week 8 12. Absolute Values And Change From Baseline In Serum Alternative Pathway Activity At Week 8 13. Plasma Factor D Concentration Over Time 14. Serum Complement Component 3 Concentration Over Time 15. Serum Classical Pathway Activity Over Time
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- week 8 - baseline through week 8 |
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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 | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Korea, Democratic People's Republic of |
Taiwan |
Canada |
Serbia |
United States |
Germany |
Italy |
Spain |
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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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The date of the last visit of the last randomized participant in the study |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 23 |