Descartes-08 for Myasthenia Gravis

Recruiting at 20 trial locations

Overseen By Michael Rivner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cartesian Therapeutics

Must be taking: Immunosuppressive drugs

Disqualifiers: Chronic illness, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called Descartes-08 CAR T-cells in patients with Generalized Myasthenia Gravis. The treatment involves modifying the patient's own immune cells to better attack the cells causing their muscle weakness. The goal is to see if this approach is safe and effective.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that immunosuppressive drugs must be deemed necessary by the investigator, which suggests you may continue them if approved by the study team.

What data supports the effectiveness of the treatment Descartes-08 for Myasthenia Gravis?

Research on new treatments for myasthenia gravis (MG) suggests that therapies like chimeric antigen receptor T (CAR-T) cell therapy, which is similar to Descartes-08, may offer faster relief and fewer side effects compared to traditional treatments. These therapies target specific immune processes involved in MG, potentially leading to long-term improvement. ^{1 2 3 4 5}

Is Descartes-08 (Anti-BCMA CAR-T cell therapy) generally safe for humans?

There is a report of a patient developing a movement disorder similar to Parkinson's disease after receiving a BCMA-targeted CAR-T cell therapy, which suggests that this treatment may have neurological side effects. Close monitoring of patients receiving this therapy is recommended due to these potential risks. ^{6 7 8 9 10}

How is the Descartes-08 treatment different from other treatments for myasthenia gravis?

Descartes-08 is a unique treatment for myasthenia gravis because it uses a type of cell therapy called CAR-T cell therapy, which involves modifying a patient's own immune cells to better target and attack specific cells involved in the disease. This approach is different from traditional treatments that often involve medications to suppress the immune system or manage symptoms. ^{3 4 11 12 13}

Eligibility Criteria

This trial is for adults over 18 with Generalized Myasthenia Gravis (MG), a condition causing muscle weakness. Participants must be taking immunosuppressive drugs, as deemed necessary by the study's doctor. It's not for those with major unmanaged chronic illnesses or pregnant/lactating individuals.

Inclusion Criteria

People who test negative for certain antibodies are allowed to participate.

I have been diagnosed with Generalized Myasthenia Gravis.

I have been diagnosed with Generalized Myasthenia Gravis.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation

Up to three ascending doses of Descartes-08 will be administered to each of 3 to 6 patients, staggered at least 21 days apart with a safety review between each dose

9 weeks

Randomized Control Trial

Patients receive up to 6 doses in three different schedules depending on the arm they were enrolled into and will be monitored for safety and tolerability

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• Descartes-08

Trial Overview The trial is testing Descartes-08 CAR-T cells to see if they are safe and can help improve symptoms in patients with MG. This Phase IIb study will give participants this new type of cell therapy that's designed to target and modify their immune system.

Participant Groups

Group I: Phase IIa Expansion Experimental Treatment 1 Intervention

Generalized Myasthenia Gravis

Group II: Phase 1b Dose-Escalation Experimental Treatment 1 Intervention

Generalized Myasthenia Gravis

Group III: Phase IIb Randomized Control Trial Placebo Group 1 Intervention

Generalized Myasthenia Gravis

Descartes-08 is already approved in United States for the following indications:

Approved in United States as Descartes-08 for:

• Generalized Myasthenia Gravis (MG)
• Systemic Lupus Erythematosus (SLE)
• Juvenile Dermatomyositis (JDM)

Who Is Running the Clinical Trial?

Cartesian Therapeutics

Lead Sponsor

Trials

10

Recruited

300+

Findings from Research

Eculizumab (ECU) treatment in patients with acetylcholine receptor autoantibody positive generalized myasthenia gravis (AChR MG) leads to significant changes in adaptive immunity, including reduced activation markers in memory CD4+ T cells and increased regulatory T cell populations, suggesting a modulation of immune response.

The study, involving 3 patients before and after at least 3 months of stable ECU therapy, indicates that ECU not only inhibits the complement system but also affects lymphocyte populations, enhancing our understanding of its mechanism of action in treating MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular changes in eculizumab early responders with generalized myasthenia gravis. Li, Y., Yi, JS., Howard, JF., et al.[2021]

New targeted therapies for myasthenia gravis (MG) show promise in providing faster relief and fewer side effects compared to traditional immunosuppressive treatments, which can take months to work and often have intolerable long-term effects.

These novel agents, including complement C5 inhibitors and B cell depleting therapies, have the potential to achieve sustained remission in MG patients, representing a significant advancement in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Treatments in Myasthenia Gravis. Menon, D., Barnett, C., Bril, V.[2020]

In a study of 17 patients with refractory myasthenia gravis, 65% achieved significant improvement after receiving repeated low-dose rituximab treatment, indicating its efficacy in managing this condition.

The treatment protocol, guided by monitoring CD19+ B-cell levels, suggests that low-dose rituximab could be a cost-effective option for patients, although further research is needed to optimize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis. Choi, K., Hong, YH., Ahn, SH., et al.[2022]

In a study of 32 patients with refractory myasthenia gravis, daily administration of 3 mg tacrolimus for one year significantly improved clinical symptoms, as evidenced by reductions in various clinical scores and a decreased need for prednisone.

Tacrolimus treatment was associated with significant changes in soluble costimulatory molecules and IL-2 levels, suggesting these molecules could serve as potential biomarkers for monitoring the disease and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tacrolimus on soluble costimulatory molecules in patients with refractory myasthenia gravis. Wu, H., Chen, L., Zhou, X., et al.[2023]

In a study of 128 myasthenia gravis patients who underwent thymectomy, 68.8% showed improvement after an average follow-up of about 52 months, indicating that thymectomy can be an effective treatment for many patients.

The presence of thymoma was identified as a significant predictor of a suboptimal clinical outcome post-surgery, suggesting that patients with thymomatous myasthenia gravis may require closer monitoring and additional treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of Suboptimal Outcome Following Thymectomy in Myasthenia Gravis. Shreedhara, AS., Nair, SS., Unnikrishnan, M., et al.[2022]

Checkpoint inhibitors targeting CTLA-4 and PD-1 are standard treatments for metastatic melanoma, but they can lead to serious side effects, including neurological complications like myasthenia gravis.

This report highlights a rare case of myasthenia gravis resulting from the combination of PD-1 and CTLA-4 blockade, which, unlike most cases, had a favorable clinical outcome, suggesting that not all cases of this complication are severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Myasthenia Gravis Following PD-1/CTLA-4 Combination Checkpoint Blockade in a Patient With Metastatic Melanoma. Werner, JM., Schweinsberg, V., Schroeter, M., et al.[2020]

Immune checkpoint inhibitors, like durvalumab, can lead to serious side effects, including exacerbations of myasthenia gravis, as demonstrated in a case study of an 82-year-old woman with non-small cell lung cancer.

The patient experienced severe symptoms such as diplopia, dyspnea, and generalized weakness after treatment, requiring high-dose steroids and plasmapheresis for management, highlighting the need for careful monitoring in patients with pre-existing autoimmune conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Interesting Case Report of Myasthenia Gravis Exacerbation Induced by Durvalumab. Abidoye, O., Kim, N., Fombi, J.[2022]

A patient with multiple myeloma developed a progressive movement disorder resembling parkinsonism after receiving BCMA-targeted CAR-T cell therapy, indicating a potential side effect of this treatment.

The presence of BCMA on neurons and astrocytes in the patient's brain suggests that the therapy may have on-target effects, highlighting the need for careful neurological monitoring in patients undergoing BCMA-targeted T cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Van Oekelen, O., Aleman, A., Upadhyaya, B., et al.[2022]

Nivolumab, a checkpoint inhibitor used for treating squamous cell carcinoma of the bladder, has been associated with the rare immune-related adverse effect of myasthenia gravis (MG), as demonstrated in a new case report.

A review of the literature revealed 10 cases of MG following treatment with PD-1 inhibitors, highlighting the need for clinicians to be aware of this potential side effect, especially since steroid treatment for MG can worsen symptoms in nearly half of the cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myasthenia Gravis After Nivolumab Therapy for Squamous Cell Carcinoma of the Bladder. Chang, E., Sabichi, AL., Sada, YH.[2022]

A patient with severe refractory myasthenia gravis (MG) underwent high-dose chemotherapy and autologous hematopoietic cell transplantation (HDIT/HCT) after failing multiple treatments, and showed significant clinical improvement within days, remaining symptom-free for 1 to 2 years post-treatment.

Despite the persistence of autoantibodies against acetylcholine receptors, the treatment led to a complete response in disease activity, suggesting that cell-mediated mechanisms may play a crucial role in refractory MG cases and warrant further investigation in a phase 2 clinical trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remission of severe myasthenia gravis after autologous stem cell transplantation. Schlatter, MI., Yandamuri, SS., O'Connor, KC., et al.[2023]

Nivolumab can induce myasthenia gravis (MG) in patients, with symptoms typically appearing after the second treatment cycle; common symptoms include ptosis, diplopia, and dyspnea, affecting 71.6% and 44.8% of patients respectively.

Despite the serious nature of nivolumab-induced MG, 68.7% of patients showed recovery or improvement after stopping the drug and receiving immunosuppressive therapy, highlighting the importance of timely diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical characteristics, treatment and outcome of nivolumab-induced myasthenia gravis. Wang, C., Zeng, H., Fang, W., et al.[2023]

In a study of six patients with myasthenia gravis (MG) treated long-term with intravenous immunoglobulin (IVIG), all patients maintained a functional status better than class 2 on the University of Virginia modification of Ossermann's scale over two years, indicating effective management of their condition.

The treatment was well tolerated with no complications reported, suggesting that IVIG can be a safe and convenient long-term therapy for selected MG patients, especially when other medications are reduced or eliminated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis. Wegner, B., Ahmed, I.[2019]

In a study of 990 myasthenia gravis patients, 8.5% were identified as drug-refractory, meaning their condition did not improve with corticosteroids and multiple immunosuppressive agents, highlighting a significant challenge in treatment.

Among drug-refractory patients, only 42.9% achieved remission or minimal symptoms after a mean follow-up of 9.8 years, compared to 79.8% of non-drug-refractory patients, indicating a need for new, more effective treatments for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome. Cortés-Vicente, E., Álvarez-Velasco, R., Pla-Junca, F., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cellular changes in eculizumab early responders with generalized myasthenia gravis. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Treatments in Myasthenia Gravis. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Repeated low-dose rituximab treatment based on the assessment of circulating B cells in patients with refractory myasthenia gravis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of tacrolimus on soluble costimulatory molecules in patients with refractory myasthenia gravis. [2023]

5. India pubmed.ncbi.nlm.nih.gov

Determinants of Suboptimal Outcome Following Thymectomy in Myasthenia Gravis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Myasthenia Gravis Following PD-1/CTLA-4 Combination Checkpoint Blockade in a Patient With Metastatic Melanoma. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

An Interesting Case Report of Myasthenia Gravis Exacerbation Induced by Durvalumab. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Myasthenia Gravis After Nivolumab Therapy for Squamous Cell Carcinoma of the Bladder. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Remission of severe myasthenia gravis after autologous stem cell transplantation. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Clinical characteristics, treatment and outcome of nivolumab-induced myasthenia gravis. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Drug-refractory myasthenia gravis: Clinical characteristics, treatments, and outcome. [2022]