Generalized Myasthenia Gravis (gMG), Refractory gMG
Conditions
Keywords
Generalized Myasthenia Gravis (gMG), Refractory gMG, Eculizumab
Brief summary
This is an open-label, single-arm, multi-center study to evaluate the efficacy, safety, PK, PD, and immunogenicity of eculizumab in Chinese participants with refractory gMG. Approximately 15 participants will be enrolled in the study.
Detailed description
This post-approval study is an open-label, single-arm, multi-center study to evaluate the efficacy, safety, PK, PD, and immunogenicity of eculizumab in Chinese participants with refractory gMG. There will be 3 periods in this study: Screening Period (up to 4 weeks), Treatment Period (26 weeks, including an Induction Phase and a Maintenance Phase), and Safety Follow-up Period (8 weeks). The overall study duration for an individual participant is estimated to be up to 38 weeks. Approximately 15 participants will be enrolled in the study.
Interventions
DRUGEculizumab
Participants will receive Eculizumab via intravenous (IV) infusion.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MG must be made by the following tests: 1. Positive serologic test for anti-AChR Abs as confirmed at Screening, and 2. One of the following: 1. Abnormal neuromuscular transmission demonstrated by repetitive nerve stimulation, or 2. History of positive anticholinesterase test, eg, neostigmine test, or 3. Participant has demonstrated improvement in MG signs on oral cholinesterase inhibitors as assessed by the treating physician * MGFA Clinical Classification Class II to IV at Screening * MG-ADL total score must be ≥ 6 at Screening and Day 1 * Participants who have: 1. Failed treatment with 2 or more ISTs over one year (either in combination or as monotherapy), ie, continue to have impairment ADLs (persistent weakness, experience crisis, or unable to tolerate IST) despite ISTs or, 2. Failed at least one IST and require chronic PE or IVIg to control symptoms, ie, participants who require PE or IVIg on a regular basis for the management of muscle weakness at least 2 cycles over last 12 months
Exclusion criteria
* Any untreated thymic malignancy, carcinoma, or thymoma * History of thymectomy or any other thymic surgery within 6 months prior to Screening. Participants with a history of treated thymic malignancy or carcinoma are eligible if they meet all of the following conditions: 1. Treatment completed \> 5 years prior to the Screening Visit 2. No recurrence within the 5 years prior to the Screening Visit 3. No radiological indication of recurrence in a computed tomography (CT) or magnetic resonance imaging (MRI) scan, including administration of intravenous (IV) contrast, performed within 6 months of first dose on Day 1 * Weakness only affecting ocular or peri-ocular muscles (MGFA Class I) * MG crisis at Screening (MGFA Class V). However, such participants may be rescreened with Alexion approval once they are treated and medically stable, in the opinion of the Investigator * History of N meningitidis infection or unresolved meningococcal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the efficacy of eculizumab in the treatment of refractory gMG based on the improvement in the MG-ADL | from baseline at Week 26 | The mean change of Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) total score from baseline at Week 26 along with 2-sided 95% CI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the efficacy of eculizumab in the treatment of refractory gMG by MGC | from baseline at Week 26 | The mean change of myasthenia gravis composite (MGC) total score from baseline at Week 26 along with 2-sided 95% CI |
| To assess the efficacy of eculizumab in the treatment of refractory gMG by MG-QoL 15r | from baseline at Week 26 | The mean change of revised Myasthenia Gravis Quality of Life 15-Item Scale (MG-QoL 15r scale) from baseline at Week 26 along with 2-sided 95% CI |
| To assess the efficacy of eculizumab in the treatment of refractory gMG by MG-ADL responder status | from baseline at Week 26 | The proportion of participants who achieve the Myasthenia Gravis Activities of Daily Living Profile (MG-ADL) response at Week 26, along with the 2-sided 95% CI |
| To assess the efficacy of eculizumab in the treatment of refractory gMG by QMG responder analysis | from baseline at Week 26 | The proportion of participants who achieve the quantitative myasthenia gravis (QMG) response at Week 26, along with the 2-sided 95% CI |
| To assess the efficacy of eculizumab in the treatment of refractory gMG by QMG | from baseline at Week 26 | The mean change of quantitative myasthenia gravis (QMG) total score from baseline at Week 26 along with 2-sided 95% CI |
| To characterize the PK of eculizumab in participants with refractory gMG | from baseline at Week 26 | Mean serum eculizumab concentrations at all scheduled visits |
| To characterize the PD of eculizumab in participants with refractory gMG | from baseline at Week 26 | Mean changes in serum free complement component 5 (C5) concentrations at all scheduled visits |
| To characterize the immunogenicity of eculizumab in participants with refractory gMG | from baseline at Week 26 | Proportion of treatment-emergent anti-drug antibody (ADA) positive participants |
| To assess the safety and tolerability of eculizumab in the treatment of refractory gMG | from baseline at Week 26 | Incidence of AEs, SAEs, and AEs leading to study intervention discontinuation (onset after first infusion) |
Countries
China
Outcome results
None listed