CAR T-Cell Therapy for Myasthenia Gravis

Recruiting at 13 trial locations

Overseen By Kyverna Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Kyverna Therapeutics

Must be taking: Glucocorticoids, Immunotherapies

Must not be taking: Anti-coagulation agents

Disqualifiers: Cardiac disease, Infections, Dementia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KYV-101, which uses CAR T-cell therapy, to help people with Myasthenia Gravis, a condition that causes muscle weakness. Researchers aim to determine if this treatment can improve symptoms for those who haven't found success with other therapies. Participants may receive the new treatment or continue standard care, with an option to switch later. Ideal candidates for this trial are individuals who have struggled with Myasthenia Gravis, have specific autoantibodies, and have tried multiple treatments without success. As a Phase 2, Phase 3 trial, this study evaluates the treatment's effectiveness in a larger group and represents the final step before FDA approval, offering hope for those seeking new options.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of glucocorticoids and/or other immunotherapies for at least 1 month before screening, and azathioprine for at least 2 months. You also need to maintain your current dose of acetylcholinesterase inhibitors for at least 2 weeks before screening.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that KYV-101, a type of CAR T-cell therapy, is designed to be both potent and well-tolerated by the body. In earlier studies, patients with autoimmune diseases improved after receiving KYV-101, suggesting the treatment is effective and potentially safe.

Reports from these studies indicate that KYV-101 is generally safe, with most patients not experiencing serious side effects. However, as with any treatment, some risks remain. Consulting a healthcare provider is important to understand these risks. Overall, the information to date appears promising for KYV-101's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myasthenia gravis?

Researchers are excited about KYV-101 CAR T-Cell Therapy for myasthenia gravis because it introduces a groundbreaking approach to treatment by harnessing the power of the immune system. Unlike standard treatments such as acetylcholinesterase inhibitors or immunosuppressants, KYV-101 uses engineered T-cells to specifically target and eliminate the problematic cells causing the disease. This targeted action offers the potential for a more precise and effective treatment, with the possibility of longer-lasting results and fewer side effects. By directly modifying the immune cells, this therapy could transform the way myasthenia gravis is managed, providing hope for patients who have not responded well to traditional therapies.

What evidence suggests that KYV-101 might be an effective treatment for Myasthenia Gravis?

Research shows that KYV-101, a therapy using modified immune cells, may help treat autoimmune diseases like myasthenia gravis. In this trial, participants will receive KYV-101 CAR-T cells, with some undergoing lymphodepletion conditioning as part of their treatment. Studies have found significant and lasting improvements in patients with autoimmune conditions after just one dose of KYV-101. This therapy targets and reduces certain immune cells thought to contribute to myasthenia gravis. Early results suggest that KYV-101 can reset the immune system, potentially reducing symptoms. This treatment aims to change how myasthenia gravis is managed, offering new hope for patients. ^{1 2 3 4 5}

Who Is on the Research Team?

MD

Principal Investigator

Kyverna Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for individuals with Myasthenia Gravis, specifically those who have autoantibodies to AChR and MuSK. Participants should be experiencing moderate to severe muscle weakness (MGFA Class IIB-IV).

Inclusion Criteria

My myasthenia gravis is moderate to severe.

I have been diagnosed with MG and have antibodies to AChR and MuSK.

I meet the main requirements to join the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Conditioning

Participants undergo lymphodepletion conditioning prior to receiving KYV-101 CAR-T cells

1-2 weeks

Treatment

Participants receive KYV-101 CAR-T cell therapy

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• KYV-101

Trial Overview The study is testing KYV-101, a type of CAR T-cell therapy designed to target CD19 on immune cells, alongside a standard treatment that reduces the number of immune cells (lymphodepletion regimen).

How Is the Trial Designed?

Group I: KYV-101 Treatment Experimental Treatment 2 Interventions

Phase 3

Group II: KYV-101 CAR-T cells with lymphodepletion conditioning Experimental Treatment 2 Interventions

Phase 2: Dosing with KYV-101 CAR-T cells

Group III: Standard of Care Active Control 3 Interventions

Phase 3 Optional crossover to receive KYV-101 Treatment after 24 weeks

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

Who Is Running the Clinical Trial?

Kyverna Therapeutics

Lead Sponsor

Trials

11

Recruited

320+

Published Research Related to This Trial

The 'Guided Missile' strategy uses genetically engineered dendritic cells to specifically target and eliminate T cells that respond to acetylcholine receptors (AChR) in myasthenia gravis (MG), minimizing damage to the overall immune system.

In both lab and animal studies, this approach significantly reduced AChR antibodies in treated mice, suggesting a promising method for translating this treatment to human patients with MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific immunotherapy of experimental myasthenia gravis in vitro and in vivo: the Guided Missile strategy. Sun, W., Adams, RN., Miagkov, A., et al.[2021]

High-dose cyclophosphamide treatment (50 mg/kg/day for 4 days) has shown marked improvement in three patients with refractory myasthenia gravis (MG), allowing for a significant reduction in their immunosuppressive medications.

The treatment was well-tolerated, led to decreased levels of acetylcholine receptor (AChR) antibodies in two patients, and resulted in no recurrence of symptoms over a follow-up period of up to 3.5 years, suggesting it may be a safe and effective option for selected patients with MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of refractory myasthenia: "rebooting" with high-dose cyclophosphamide. Drachman, DB., Jones, RJ., Brodsky, RA.[2022]

A therapeutic vaccine targeting the cytoplasmic domains of human AChR subunits was found to be safe and effective in preventing and reversing chronic experimental autoimmune myasthenia gravis (EAMG) in rats, indicating its potential for treating myasthenia gravis (MG).

The vaccine not only prevented the onset of EAMG but also led to a long-lasting change in the immune response, shifting from a pathogenic antibody type (IgG2b) to a non-pathogenic type (IgG1), which may contribute to long-term resistance against the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigen-specific immunotherapeutic vaccine for experimental autoimmune myasthenia gravis. Luo, J., Lindstrom, J.[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]

Myasthenia gravis patients with muscle-specific tyrosine kinase (MuSK) antibodies have distinct treatment needs, and while they often respond poorly to acetylcholinesterase inhibitors, corticosteroids like prednisone are recommended as a primary treatment, starting at 1.5-2 mg/kg/day.

Rituximab shows promise for severe cases of MuSK myasthenia gravis, and acute exacerbations can be effectively treated with plasma exchange, which is generally more effective than IVIg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of MuSK-Associated Myasthenia Gravis. El-Salem, K., Yassin, A., Al-Hayk, K., et al.[2022]

Two peptide analogues, 204GLY and 207ALA, were found to inhibit T-cell responses in myasthenia gravis (MG) patients, suggesting they can modulate immune responses effectively.

These analogues not only blocked T-cell activation in vitro but also demonstrated the ability to inhibit immune priming in vivo, indicating their potential as therapeutic agents for MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered peptide ligands of a myasthenogenic epitope as modulators of specific T-cell responses. Kirshner, SL., Zisman, E., Fridkin, M., et al.[2019]

A new chimeric human-mouse model of myasthenia gravis was developed using severe combined immunodeficiency mice, which allows for the study of human immune responses by incorporating human peripheral blood lymphocytes.

This model successfully reproduced key features of human myasthenia gravis, such as the presence of anti-acetylcholine receptor antibodies and changes at the muscle end-plates, providing a valuable tool for researching autoimmune mechanisms and potential treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The human-severe combined immunodeficiency myasthenic mouse model: a new approach for the study of myasthenia gravis. Martino, G., DuPont, BL., Wollmann, RL., et al.[2022]

A 17-year-old boy with severe myasthenia gravis (MG) experienced complete resolution of muscle weakness and no longer required medication 40 months after undergoing matched sibling peripheral blood stem cell transplantation, although some symptoms like ophthalmoplegia persisted.

The case suggests that while anti-acetylcholine receptor antibodies remain elevated post-transplant, they do not necessarily correlate with MG symptoms, indicating that other immune mechanisms may play a role in the disease's pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic cell transplantation for refractory myasthenia gravis. Strober, J., Cowan, MJ., Horn, BN.[2013]

Three patients with severe anti-muscle-specific kinase (MuSK) myasthenia gravis, who were unresponsive to multiple treatments, underwent autologous hematopoietic stem cell transplant (HSCT) and achieved significant improvement, with symptoms nearly eliminated for up to 5.5 years.

The treatment was associated with manageable side effects, and all patients reported a dramatic improvement in their quality of life, suggesting that HSCT could be a viable option for those with refractory MuSK myasthenia gravis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous hematopoietic stem cell transplant for the treatment of refractory myasthenia gravis with anti-muscle specific kinase antibodies. Beland, B., Hahn, C., Jamani, K., et al.[2023]

Engineered T cells expressing a MuSK chimeric autoantibody receptor (MuSK-CAART) effectively targeted and depleted B cells producing harmful anti-MuSK autoantibodies, showing similar efficacy to existing therapies without the need for chronic immunosuppression.

In a mouse model of myasthenia gravis, MuSK-CAART specifically reduced anti-MuSK IgG levels while preserving overall B cell counts, indicating targeted action without significant off-target effects, paving the way for a phase 1 clinical study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Oh, S., Mao, X., Manfredo-Vieira, S., et al.[2023]

Recent advances in understanding the immune mechanisms of myasthenia gravis (MG) have led to the development of targeted immune therapies, which may provide faster and more effective responses compared to traditional immunosuppressive treatments.

While there are promising new therapies in various stages of clinical development, more research is needed to determine the best timing, duration, and long-term safety of these treatments, indicating a shift towards personalized immunotherapy for MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging drugs for the treatment of myasthenia gravis. Menon, D., Urra Pincheira, A., Bril, V.[2022]

Citations

1. ir.kyvernatx.com ir.kyvernatx.com/news-releases/news-release-details/kyverna-therapeutics-announces-positive-interim-phase-2-data

Release Details KYV-101 is a fully human, autologous, CD19 CAR T-cell therapy with CD28 co-stimulation, designed for potency and tolerability, which is under ...

2. fiercebiotech.com fiercebiotech.com/biotech/kyverna-links-car-t-improved-autoimmune-outcomes-small-trial

Kyverna links CAR-T to autoimmune improvements in ... Kyverna saw deep, sustained improvements in autoimmune disease patients who received a single dose of its CAR T-cell therapy KYV-101.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06193889

KYSA-6: A Study of Anti-CD19 Chimeric Antigen Receptor ... KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with myasthenia gravis (MG). Official Title. KYSA-6: A Phase 2/3, ...

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000210631

Design of KYSA-6, a Phase 2, Open-label, Multicenter ... KYV-101 is a novel therapy with the potential to change the treatment paradigm through deep B-cell depletion and immune reset with a single infusion.

5. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(23)00375-7/fulltext

Anti-CD19 CAR T cells for refractory myasthenia gravis Myasthenia gravis: long-term correlation of binding and bungarotoxin blocking antibodies against acetylcholine receptors with changes in disease severity.