CD-19 CAR T for Stiff Person Syndrome

Recruiting at 2 trial locations

Overseen By Kyverna Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kyverna Therapeutics

Disqualifiers: Stroke, Seizure, 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

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Anti-CD19 CAR T-cell therapy, a type of immunotherapy, for individuals with Stiff Person Syndrome, which causes severe muscle stiffness and spasms. The goal is to determine if this therapy can help those who haven't found relief from other treatments. Suitable candidates for this trial have experienced frequent muscle stiffness and spasms triggered by unexpected noises and have not responded well to other treatments. Participants should not have other neurological conditions that could cause similar symptoms. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from a promising new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that KYV-101, a type of CAR T-cell therapy, has a promising safety record from earlier studies. CAR T-cell therapy involves modifying a patient's immune cells to enhance their ability to fight disease. In one study, a 62-year-old woman with a difficult-to-treat condition called stiff person syndrome received this therapy. She experienced improvements in her symptoms and did not encounter any serious side effects.

This treatment is currently in Phase 2 trials, indicating it has already passed initial safety tests in smaller groups. It is now being tested in more people to evaluate its effectiveness and safety. Since it has reached Phase 2, earlier tests likely did not reveal any major safety concerns. Significant safety issues would have prevented the treatment from advancing to this phase. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Stiff Person Syndrome?

Unlike the standard treatments for Stiff Person Syndrome, which often include medications like benzodiazepines and muscle relaxants that mainly manage symptoms, the CD-19 CAR T-cell therapy represents a novel approach to tackling the condition. This therapy involves genetically modifying a patient's own T-cells to target and destroy B-cells that may be contributing to the autoimmune response underlying the syndrome. Researchers are excited about this treatment because it offers a targeted mechanism of action that could potentially address the root cause of the condition rather than just alleviating its symptoms. This innovative approach could lead to longer-lasting relief and improved quality of life for patients.

What evidence suggests that Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy might be an effective treatment for Stiff Person Syndrome?

Research has shown that Anti-CD19 CAR T-Cell therapy might help people with Stiff Person Syndrome (SPS). In one case, a patient with severe SPS experienced reduced leg stiffness and improved walking speed and distance after receiving this therapy. Studies suggest that the therapy targets specific immune cells that may cause SPS symptoms. Some patients have improved even when other treatments failed. Overall, early results are promising for those with SPS that hasn't responded to other treatments. Participants in this trial will receive KYV-101 CAR-T cells with lymphodepletion conditioning as part of the study treatment. ^{2 4 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Kyverna Therapeutics

Are You a Good Fit for This Trial?

This trial is for people with Stiff Person Syndrome who haven't improved after at least one immunomodulatory therapy. They should experience spasms triggered by noise, touch, or stress and have high levels of specific antibodies in their blood or CSF. Participants need to be able to walk and not have any other neurological diseases causing stiffness.

Inclusion Criteria

My muscles are constantly tense without relaxation.

My stiffness index is 2 or higher.

I have stiffness in my limbs and trunk that makes bending hard.

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 week

Treatment

Participants receive KYV-101 CAR T cell therapy

1 day

Follow-up

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

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

Trial Overview The study tests a new treatment using Anti-CD19 Chimeric Antigen Receptor T Cell (CAR T) Therapy following a standard lymphodepletion regimen. It's designed for those whose Stiff Person Syndrome hasn't responded to usual treatments.

How Is the Trial Designed?

Group I: KYV-101 CAR-T cells with lymphodepletion conditioning Experimental Treatment 1 Intervention

Dosing with KYV-101 CAR T cells

Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Axicabtagene ciloleucel (Yescarta) for:

• Relapsed or refractory large B-cell lymphoma
• Relapsed or refractory follicular lymphoma

Approved in United States as Tisagenlecleucel (Kymriah) for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia
• Relapsed or refractory diffuse large B-cell lymphoma

Approved in United States as Lisocabtagene maraleucel (Breyanzi) for:

• Relapsed or refractory large B-cell lymphoma

Approved in European Union as Axicabtagene ciloleucel (Yescarta) for:

• Relapsed or refractory diffuse large B-cell lymphoma
• Relapsed or refractory follicular lymphoma

Approved in European Union as Tisagenlecleucel (Kymriah) for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia
• Relapsed or refractory diffuse large B-cell lymphoma

Approved in European Union as Lisocabtagene maraleucel (Breyanzi) for:

• Relapsed or refractory large B-cell lymphoma

Who Is Running the Clinical Trial?

Kyverna Therapeutics

Lead Sponsor

Trials

11

Recruited

320+

Published Research Related to This Trial

Tocilizumab is the only interleukin inhibitor currently approved for treating cytokine release syndrome (CRS) caused by CAR-T therapy, demonstrating both efficacy and safety in this context.

Other interleukin inhibitors like siltuximab and anakinra may be beneficial when used alongside tocilizumab to further reduce the risk of severe CRS and neurotoxicity, suggesting potential for improved management of CAR-T therapy side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin Inhibitors in Cytokine Release Syndrome and Neurotoxicity Secondary to CAR-T Therapy. Ferreros, P., Trapero, I.[2022]

CART19 therapy, which targets CD19, has shown significant success in treating relapsed/refractory B cell acute lymphoblastic leukemia (ALL) in patients aged 25 and younger, making it a standard treatment for this age group.

For older adults, CART19 therapy is more complex and typically only available through clinical trials, requiring careful evaluation of treatment goals, potential for stem cell transplants, and the specific risks and benefits of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T in adult ALL: When and for whom? Connor, MP., Frey, NV.[2022]

CAR T-cell therapy is an innovative treatment for difficult-to-treat blood cancers, but there is limited research on the rehabilitation needs of patients undergoing this therapy.

Patients receiving CAR T-cell therapy often experience cognitive impairments, muscle weakness, and fatigue, suggesting that tailored rehabilitation programs could improve their quality of life and functional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation Needs for Patients Undergoing CAR T-Cell Therapy. Obaisi, O., Fontillas, RC., Patel, K., et al.[2022]

CAR.λ T cells effectively target and kill Igλ+ lymphoma cells and chronic lymphocytic leukemia (CLL) cells, showing similar antitumor activity to the established CAR.CD19 T cells in both laboratory and animal models.

Importantly, CAR.λ and CAR.κ T cells selectively deplete only the corresponding light chain-expressing normal B cells, preserving the other type, which suggests a safer approach with minimal impact on the immune system's ability to produce antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. Ranganathan, R., Shou, P., Ahn, S., et al.[2022]

CD19-targeted CAR T cell therapy has shown remarkable efficacy, achieving complete remission in 70-90% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL), highlighting its potential as a powerful treatment for B cell malignancies.

The ongoing phase I study using a non-viral gene transfer method (piggyBac-transposon system) for CD19 CAR T cell therapy in pediatric and young adult patients indicates a promising direction for expanding treatment options in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. Nakazawa, Y.[2017]

CD19-directed CAR T-cell therapy has shown promising results in treating relapsed/refractory B-cell non-Hodgkin lymphoma, with 30-40% of patients achieving durable responses in pivotal phase I/II trials, leading to FDA and EMA approvals for specific therapies.

Despite its effectiveness, the therapy is associated with significant toxicities, such as cytokine release syndrome and neurotoxicity, which can limit its use and present challenges in patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-directed CAR T-cell therapy in B-cell NHL. Kersten, MJ., Spanjaart, AM., Thieblemont, C.[2021]

Chimeric antigen receptor-modified T cells targeting CD19 showed significant clinical activity in two children with relapsed acute lymphoblastic leukemia (ALL), leading to complete remission in one patient for 11 months after treatment.

While the treatment was effective, both patients experienced severe adverse events, including cytokine-release syndrome and B-cell aplasia, highlighting the need for careful monitoring and potential additional targeting strategies due to the emergence of CD19-negative tumor cells in one patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. Grupp, SA., Kalos, M., Barrett, D., et al.[2023]

CAR T-cell therapy can lead to significant acute toxicities, particularly cytokine release syndrome (CRS) and neurotoxicity, which can result in serious complications and affect ongoing cancer treatment.

Emergency physicians need to be well-informed about these potential toxicities to provide prompt diagnosis and management, which may include supportive care and medications like tocilizumab or corticosteroids for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Chimeric Antigen Receptor (CAR) T-Cell Toxicities: A Review and Guideline for Emergency Providers. Gupta, R., Roach, C., Hryniewicki, AT., et al.[2021]

Citations

1. neurology.org neurology.org/doi/10.1212/NXI.0000000000200479

Anti-CD19 CAR T-Cell Therapy in Advanced Stiff-Person ... We report a 62-year-old female patient with a 14-year history of treatment-refractory anti–GAD-positive stiff-person syndrome (SPS) and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06588491

KYSA-8: A Study of Anti-CD19 Chimeric Antigen Receptor ... CAR-T therapy such as KYV-101 may be an effective treatment for SPS, by targeting these autoreactive B cells. Using chimeric antigen receptor (CAR) T-cell ...

3. pnas.org pnas.org/doi/10.1073/pnas.2403227121

Successful use of anti-CD19 CAR T cells in severe ... CAR T cell infusion resulted in reduced leg stiffness, drastic improvement in gait, walking speed increase over 100%, and daily walking distance improvement.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41052399

Anti-CD19 CAR T-Cell Therapy in Advanced Stiff-Person ... CAR T-cell therapy was effective at mitigating SPS symptoms, despite the long history and severe refractory disease course in our patient.

5. cell.com cell.com/cell-reports-medicine/pdf/S2666-3791(24)00541-X.pdf

Anti-CD19 CAR-T cells are effective in severe idiopathic ... First reports show beneficial effects of anti-CD19 chimeric antigen receptor (CAR)-T cell therapy in patients with autoantibody-mediated myas-.

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000210669

Design of KYSA-8, A Phase 2, Open-Label, Multicenter ... KYV-101 is a first-in-class, fully human autologous anti-CD19 CAR T-cell therapy with a promising clinical safety profile. KYV-101 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12514794/

Anti-CD19 CAR T-Cell Therapy in Advanced Stiff-Person ... We report a 62-year-old female patient with a 14-year history of treatment-refractory anti–GAD-positive stiff-person syndrome (SPS) and ...

8. kyvernatx.com kyvernatx.com/education-events/publications/

CAR T-Cell Therapy Publications A selection of leading publications and our contributions to advance the learning on CAR T-cell therapies.