Cartesian MG-001

Please refer to section 3 of the study protocol. Penn will only enroll participants into Part 3 of the study.

PRIMARY OBJECTIVES
The primary objective of Part 1 is to assess the safety, tolerability, and manufacturing feasibility of Descartes-08 in patients with GMG. Part 1 of the study follows an intra-patient dose escalation design, where Descartes- 08 will be dose-escalated within each of 3 to 6 patients; the patients will also be staggered at least 21 days apart. In Part 2, patients will receive up to 6 doses of Descartes-08 at a dose established as safe and tolerable in Part 1; each dose will be administered in 3 different schedules in seropositive patients and in a weekly schedule to seronegative patients to assess the safety and tolerability of a multiple (repeated) dosing schedule up to 1 year. In Part 3, the primary objective is to compare the effect of Descartes-08 versus placebo, as measured by the change in MG Activities of Daily Living (MG ADL) score from baseline to Week 12.

SECONDARY OBJECTIVES

1. 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);
2. 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).
3. 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).
4. 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 t o Descartes-08 (Part 3 only).

EXPLORATORY OBJECTIVES

1. Determine the change from baseline in the titer of myasthenia gravis-specific autoantibodies in seropositive patients (Part 3 only).
2. Determine the change in 4 Immunoglobulin types (IgG, IgM, IgA, IgE) and vaccine titers in all patients (Part 3 only);
3. Evaluate the presence, frequency and titer of anti-mouse human antibody (HAMA) following single or multiple infusions of Descartes-08;
4. Assess standard pharmacokinetic parameters of Descartes-08 in blood following single or multiple infusions by a validated qPCR assay to the CAR construct; and
5. Evaluate biomarkers of safety and efficacy (i.e., serum cytokine levels, serum inflammatory markers, plasma BCMA levels, vaccination (within the past 3 years) titers, and IgG subtypes) following single or multiple infusions of Descartes-08.
6. Evaluate the changes in the immunophenotype and immunosuppressive function of the peripheral T-cells in all patients; and
7. Evaluate the changes in the peripheral B-cell and T-cell populations in all patients. Please refer to page 10 of the study protocol. Penn will only enroll participants into Part 3 of the study.

PRIMARY ENDPOINTS
The primary endpoint in Part 1 is the Maximum Tolerated Dose (MTD) defined as the Dose Level at which no more than one patient has shown Dose-Limiting Toxicity (DLT) after Part 1 of the study is completed. Completed means that 3 patients completed the study without a DLT; or 6 patients completed the study with no more than 1 DLT. If the number of cells patients, then the highest achievable (and safe) dose level will be determined as Maximum Feasible Dose (MFD). The primary endpoint in Part 2 is the type and frequency of treatment emergent adverse events. T

You may be eligible for this study if you meet the following criteria:

• Conditions:
  Medical Research
• Age: - 99 Years
• Gender: All