A Phase III, Open-Label, Extension Trial of ECU-MG-301 to Evaluate the Safety and Efficacy of Eculizumab in Subjects with Refractory Generalized Myasthenia Gravis (gMG).
Detailed DescriptionThis is a phase III, open label, extension trial of ECU-MG-301(HS-13-00805) to evaluate the safety and efficacy of Eculizumab in subjects with refractory generalized myasthenia gravis (gMG). Eculizumab is a humanized monoclonal antibody that was derived from the murine anti-human C5 antibody m5G1.1. Myasthenia Gravis is a rare, debilitating, acquired autoimmune disease of the neuromuscular junction (NMJ), clinically characterized by weakness and fatigability of skeletal muscle. Since complement activation plays a pivotal role in the pathophysiology of MG, eculizumab, a terminal complement inhibitor, as such may benefit patients who continue to have generalized weakness and bulbar signs and symptoms despite current standard of care. The primary objective of this trial is to evaluate the long-term safety of eculizumab in subjects with refractory gMG. Subjects who complete the 26-week treatment period (Visit 17) in the ECU-MG-301(HS-13-00805) trial may potentially enter this extension trial. There will be 3 periods in this study, Blind Induction Phase, Open-Label Maintenance Phase and Safety Follow-up Period. To preserve the blinded nature of the ECU-MG-301 trial, all subjects must undergo a blind induction phase and will receive blinded Investigational Product (IP) weekly for four (4) doses. Patients who were randomized to the placebo arm in the ECU-MG-301 trial will receive 4 vials IP (3 vials/900 mg eculizumab plus 1 vial placebo) at Visits 1 to 4. Patients who were randomized to the eculizumab arm in the ECU-MG-301 trial will continue to receive 4 vials IP (1200 mg eculizumab) every two weeks at Visits 1 and 3 and placebo at Visits 2 and 4. All subjects will receive open-label eculizumab (4 vials/1200 mg) every 2 weeks during the open level maintenance phase. On-Trial Rescue Therapy (high dose corticosteroid,plasmapheresis /plasma exchange (PE) or Intravenous Immunoglobulin,) will be allowed if a subject experiences clinical deterioration as defined in this protocol. For a subject who is discontinued from this trial, a follow-up visit for safety evaluation will be required. Primary efficacy endpoint is Safety and tolerability of eculizumab. Secondary Efficacy Endpoints will include the total change of QMG (Quantitative Myasthenia Gravis) score and total change of Myasthenia Gravis Composite (MGC) score. Safety analyses will be performed on the Safety Population and the Extension Safety Population includes all subjects who receive at least 1 dose of IP (eculizumab or Placebo). There is no interim analysis planned for this trial.
PhasePhase 3 - a treatment has shown activity against a particular disease, where it is either added to existing treatment or compared to the standard treatment.
Inclusion and Exclusion Criteria
- Subject has completed the ECU-MG-301 trial.
- Subject has given written informed consent.
- Subject is willing and able to comply with the protocol requirements for the duration of the trial.
- Female subjects of child-bearing potential must have a negative pregnancy test (serum human chorionic gonadotropin [HCG]). All subjects must practice an effective, reliable and medically approved contraceptive regimen during the trial and for up to 5 months following discontinuation of treatment.
- Subjects who withdrew from the ECU-MG-301 trial as a result of an AE related to trial drug.
- Female subjects who are pregnant, breastfeeding or intend to conceive during the course of the trial.
- Any medical condition or circumstances that, in the opinion of the Investigator, might interfere with the subject's participation in the trial, pose any added risk for the subject, or confound the assessment of the subjects.
Please contact Salma Akhter to learn more about where you can participate in this trial. Please use the contact form on the right side.