Descartes-08 CAR-T Cells in Generalized Myasthenia Gravis (MG)

Study Overview
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Brief Summary
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This is a Phase IIb study to evaluate the safety and preliminary efficacy of Descartes-08 CAR T-cells in patients with Generalized Myasthenia Gravis

Official Title
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Autologous T-Cells Expressing A Chimeric Antigen Receptor Directed To B-Cell Maturation Antigen (BCMA) In Patients With Generalized Myasthenia Gravis (MG)

Conditions
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Myasthenia Gravis, Generalized

Intervention / Treatment
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* Drug: Descartes-08


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be at least 18 years of age. Patient must have Generalized Myasthenia Gravis at the time of screening. Concomitant immunosuppressive drugs must be deemed necessary by the investigator. Seronegative Patients are included Exclusion Criteria: Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator may increase the risk to the patient. Patient is pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1b Dose-Escalation<br>Generalized Myasthenia Gravis | Drug: Descartes-08<br>* Autogolous T-cells expressing a chimeric antigen receptor directed to BCMA<br>|
| Experimental: Phase IIa Expansion<br>Generalized Myasthenia Gravis | Drug: Descartes-08<br>* Autogolous T-cells expressing a chimeric antigen receptor directed to BCMA<br>|
| Placebo Comparator: Phase IIb Randomized Control Trial<br>Generalized Myasthenia Gravis | Drug: Descartes-08<br>* Autogolous T-cells expressing a chimeric antigen receptor directed to BCMA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myasthenia Gravis -Activities of Daily Living Score | In Part 3, the primary objective is to compare the effect of Descartes-08 versus placebo, as measured by the change in MG ADL score from baseline to Week 12. In Part 1, up to three ascending doses of Descartes-08 will be administered to each of 3 to 6 patients; the patients will be staggered at least 21 days apart and will complete a safety review between each dose. In Part 2, patients will receive up to 6 doses in three different schedules depending on the arm they were enrolled into and will be monitored for up to 1 year to assess the safety and tolerability of a repeated dosing schedule. | Day 0 to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison on Descartes-08 versus placebo on QMG, MG QoL 15R, MG Composite, MG PIS | Compare the effect of Descartes-08 versus placebo on QMG, MG QoL 15R, MG Composite, and MG PIS (change from baseline to Week 12) for all randomized patients (Part 3 only). | Day 0 to Day 85 | 
| Comparison on Descartes-08 versus placebo on MG assessments in crossover patients | Compare the effect of Descartes-08 versus placebo on MG ADL, QMG, MG QoL 15R, MG Composite, and MG PIS (change from baseline to Week 12) in patients who cross over from placebo to Descartes-08 (Part 3 only). | Day 0 to Day 85 | 
| Change in titer of myasthenia specific autoantibody titers | Determine the change from baseline over a period of 24 weeks in the titer of myasthenia specific autoantibody titers, e.g. nicotinic acetylcholine receptor autoantibody (anti-nAChR) or muscle-specific tyrosine kinase autoantibody (anti- MusK or anti-Low-Density-Lipoprotein-Related-Protein4 (anti-LRP4) or anti-AChR cluster antibody and the 4 Immunoglobulin types (IgG, IgM, IgA, IgE) following single or multiple infusions of Descartes-08 in MG auto-antibody seropositive patients (Parts 1 and 2 only) | Day 0 to Day 168 | 
| Effect of single or multiple infusions of Descartes-08 on patients by standard clinical assessment scales | Quantify the clinical effect of single or multiple infusions of Descartes-08 on patients by standard clinical assessment scales (MG ADL, QMG, MG QoL 15R, MG PIS, MG Composite) over a period of 24 weeks in MG auto-antibody seropositive and seronegative patients together and separately (all parts). | Day 0 to Day 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Descartes-08, CART, CAR-T, Autoimmune, Auto-antibody, Auto antibody, chimeric antigen receptor, T cells, MG, gMG, Myasthenia Gravis, Generalized Myasthenia gravis