120 Participants Needed

CAR T-Cell Therapy for Multiple Sclerosis

KT
Overseen ByKyverna Therapeutics, Inc.
Age: 18 - 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Kyverna Therapeutics
Must be taking: Anti-CD20 mAb
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects with Refractory Primary and Secondary Progressive Multiple Sclerosis

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

The trial protocol does not specify if you need to stop taking your current medications. However, since it involves CAR T-Cell therapy, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the idea that CAR T-Cell Therapy for Multiple Sclerosis is an effective treatment?

The available research does not provide specific data on CAR T-Cell Therapy for Multiple Sclerosis. Instead, it discusses other treatments like autologous hematopoietic stem cell transplantation (HSCT) and cell-based therapies. These treatments have shown some promise in managing multiple sclerosis by resetting the immune system and potentially offering neuroprotection. However, they also come with safety concerns and unresolved questions. Without specific data on CAR T-Cell Therapy, it's difficult to compare its effectiveness to these other treatments.12345

What safety data exists for CAR T-Cell Therapy in treating Multiple Sclerosis?

CAR T-Cell Therapy, including treatments like KYV-101 and Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, has been associated with several safety concerns. Key adverse events include severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX), as identified in a cross-study safety analysis involving 1,926 subjects from various trials. The use of gammaretrovirus vectors with CD28 sequences was linked to higher rates of sNTX. Management strategies, such as cytokine-directed therapies and corticosteroids, have been associated with reduced sCRS rates. Cardiovascular events, including arrhythmias and heart failure, have also been reported, with a higher mortality rate observed in patients experiencing these events. Overall, while CAR T-Cell Therapy shows promise, it carries significant risks that require careful management.678910

Is CAR T-Cell Therapy generally safe for humans?

CAR T-Cell Therapy has shown potential for severe side effects, including cytokine release syndrome (a severe immune reaction) and neurological toxicities (nerve-related side effects). Cardiovascular events like arrhythmias (irregular heartbeats) and heart failure have also been reported, with a higher risk of these events when other side effects are present.678910

Is the treatment KYV-101 a promising treatment for Multiple Sclerosis?

Yes, KYV-101, a type of CAR T-Cell therapy, shows promise for treating Multiple Sclerosis. This treatment uses specially engineered cells to target and suppress harmful immune responses, potentially reducing the disease's impact.1112131415

How is the treatment KYV-101 different from other treatments for multiple sclerosis?

KYV-101 is a unique treatment for multiple sclerosis because it uses CAR T-cell therapy, which involves engineering the patient's own immune cells to specifically target and suppress harmful immune responses. This approach is different from traditional treatments that generally suppress the immune system without targeting specific cells.1112131415

Research Team

M

MD

Principal Investigator

Kyverna Therapeutics, Inc.

Eligibility Criteria

This trial is for people with a tough form of multiple sclerosis (MS) that hasn't improved after other treatments. Participants must have been diagnosed with primary or secondary progressive MS and shown worsening disability despite previous anti-CD20 mAB therapy.

Inclusion Criteria

I have been diagnosed with progressive MS.
My condition worsened despite anti-CD20 treatment over the last 6 months.
Key

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KYV-101 CAR T cells with lymphodepletion conditioning or anti-CD20 mAb

12 weeks
Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety, efficacy, and pharmacokinetics of KYV-101

Up to 2 years
Regular visits for safety and efficacy assessments

Treatment Details

Interventions

  • KYV-101
Trial OverviewThe study tests a new therapy using modified T-cells, called Anti-CD19 CAR T-cell therapy (KYV-101), to see if it can help manage severe MS. It's given after a standard treatment that reduces the number of immune cells in the body.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: KYV-101 CAR-T cells with lymphodepletion conditioningExperimental Treatment2 Interventions
Dosing with KYV-101 CAR T cells
Group II: Anti- CD20 mAbActive Control1 Intervention
Dosing with anti-CD20 mAb

KYV-101 is already approved in United States for the following indications:

🇺🇸
Approved in United States as KYV-101 for:
  • Refractory Lupus Nephritis
  • Stiff-Person Syndrome
  • Myasthenia Gravis
  • Diffuse Cutaneous Systemic Sclerosis (Scleroderma)
  • Primary and Secondary Progressive Multiple Sclerosis

Find a Clinic Near You

Who Is Running the Clinical Trial?

Kyverna Therapeutics

Lead Sponsor

Trials
11
Recruited
320+

Findings from Research

In a study of 41 patients with refractory multiple sclerosis, the conditioning regimen CY/rabbit ATG showed lower complication rates (40%) compared to BEAM/horse ATG (71.4%), indicating it may be a safer option for patients undergoing autologous hematopoietic stem cell transplantation.
Both regimens had similar event-free survival rates (EFS), with 58.54% overall, suggesting that while CY/rATG is less toxic, further long-term studies are needed to determine if it is equally effective in preventing disease progression.
Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG.Hamerschlak, N., Rodrigues, M., Moraes, DA., et al.[2013]
Autologous stem cell transplantation (ASCT) for progressive multiple sclerosis (MS) leads to significant changes in lymphocyte subsets, with CD4+ T-cells and T-regulatory cells not returning to baseline levels, suggesting a reset of the immune system.
After ASCT, neurological function remained stable for most patients, with a progression-free survival rate of 69% at three years, indicating that ASCT may be an effective treatment option for managing progressive MS.
Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS.Cull, G., Hall, D., Fabis-Pedrini, MJ., et al.[2020]
Current disease-modifying medications for multiple sclerosis are only partially effective and do not promote repair of the central nervous system, highlighting the need for new treatment strategies.
Cell-based therapies, such as stem cell transplantation and pharmacologic manipulation of endogenous stem cells, show promise for immune modulation and neuroprotection, but they also come with safety concerns and require further research to address methodological and ethical issues.
Cell-based therapeutic strategies for multiple sclerosis.Scolding, NJ., Pasquini, M., Reingold, SC., et al.[2023]

References

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG. [2013]
Lymphocyte reconstitution following autologous stem cell transplantation for progressive MS. [2020]
Cell-based therapeutic strategies for multiple sclerosis. [2023]
Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation. [2020]
RETRACTED: Neural Stem Cells Engineered to Express Three Therapeutic Factors Mediate Recovery from Chronic Stage CNS Autoimmunity [2023]
Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. [2022]
Associated Toxicities: Assessment and Management Related to CAR T-Cell Therapy. [2020]
[Management of adverse events of CAR-T therapy]. [2023]
Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. [2021]
Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies. [2023]
Engineered regulatory T cells expressing myelin-specific chimeric antigen receptors suppress EAE progression. [2022]
Large-scale manufacturing and characterization of CMV-CD19CAR T cells. [2022]
13.United Statespubmed.ncbi.nlm.nih.gov
Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes. [2021]
Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells. [2023]
Application of CAR-T cell technology in autoimmune diseases and human immunodeficiency virus infection treatment. [2023]