CD19 CAR T-Cell Therapy for Scleroderma

Not currently recruiting at 1 trial location

Overseen By Kyverna Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Kyverna Therapeutics

Disqualifiers: HIV, Hepatitis B/C, Neurologic disorders, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

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 aid people with scleroderma, a condition that hardens and tightens the skin and connective tissue. The goal is to determine if this therapy can improve symptoms for those with systemic sclerosis, a severe form of scleroderma. Participants will receive KYV-101 in one of two phases to identify the optimal dose and assess safety. Individuals with scleroderma symptoms for six years or less and active disease may be suitable for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, assisting researchers in understanding its effects on people.

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 KYV-101 CAR T-Cell Therapy is likely to be safe for humans?

A previous study tested KYV-101, a type of treatment called CD19 CAR T-cell therapy, on patients with systemic lupus erythematosus. The results showed it was generally well-tolerated, meaning most people did not experience serious side effects. Another study examined KYV-101 in patients with progressive multiple sclerosis. Although specific details about side effects were not provided, the treatment was considered safe enough to continue testing.

Currently, KYV-101 is in the early stages of trials for other conditions, with researchers carefully checking its safety. Early-phase trials focus on understanding a treatment's safety and potential side effects. For those considering joining a trial, it's helpful to know that this treatment has already passed the initial safety checks. ^{1 2 3 4 5}

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

Most treatments for scleroderma, such as immunosuppressants and anti-fibrotic drugs, aim to manage symptoms and slow progression. But KYV-101 offers a novel approach by employing CD19 CAR T-cell therapy, which reprograms a patient's own immune cells to specifically target and reduce the abnormal immune activity driving the disease. This precision targeting could lead to more effective control of scleroderma with potentially fewer side effects. Researchers are excited about KYV-101 because it represents a significant shift from broad immunosuppression to a more tailored and potentially transformative treatment.

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

Research has shown that KYV-101, a therapy targeting specific immune cells, produces positive results in treating autoimmune diseases. In patients with systemic lupus erythematosus, a similar treatment achieved impressive outcomes. These therapies modify a person's immune cells to attack and destroy the cells causing the disease. In this trial, participants will receive KYV-101, designed to address autoimmune diseases driven by B cells, such as systemic sclerosis. Although specific data on KYV-101 for systemic sclerosis is not yet available, its success in similar conditions is encouraging. ^{2 4 5 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Kyverna Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for people with a condition called systemic sclerosis, specifically the diffuse cutaneous type. They should be within 6 years of their first symptom that's not Raynaud's phenomenon and have active disease. Participants must also be current on vaccinations recommended for those with weakened immune systems.

Inclusion Criteria

Up to date on all recommended vaccinations per CDC or institutional guidelines for immune-compromised individuals

My skin condition was diagnosed as diffuse cutaneous SSc within the last 6 years and is still active.

I have been diagnosed with systemic sclerosis.

Exclusion Criteria

I have a serious lung condition.

I have previously received CAR-T or gene therapy.

Evidence of active hepatitis B or hepatitis C infection

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

52 weeks

Regular visits for monitoring and assessment

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, which is a type of CAR T-cell therapy targeting CD19, an antigen found on certain cells in the body. This therapy will be compared to or combined with standard treatments that reduce the number of lymphocytes (a type of white blood cell).

How Is the Trial Designed?

Group I: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2) Experimental Treatment 2 Interventions

Recommended Phase 2 Dose

Group II: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1) Experimental Treatment 2 Interventions

Dosing with KYV-101 CAR T cells

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 phase I/IIa trial of third-generation CAR T-cell therapy targeting CD19 in 15 patients with B-cell malignancies showed that the treatment was generally safe, with only 4 patients requiring hospitalization due to adverse reactions.

Six out of 15 patients achieved complete responses, indicating promising efficacy, particularly in those with a good immune status prior to treatment, suggesting that immune profiling could help identify potential responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Enblad, G., Karlsson, H., Gammelgård, G., et al.[2019]

In a study of six patients with refractory systemic lupus erythematosus (SLE), anti-CD19 CAR T cell therapy was found to be well tolerated and led to a significant reduction in inflammatory cytokines IL-6 and TNFα three months after treatment.

The therapy also resulted in a marked decrease in SLE-associated antibodies in five out of six patients, suggesting a potential mechanism for its efficacy in managing SLE symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Nunez, D., Patel, D., Volkov, J., et al.[2023]

CD19-targeted CAR Tregs, generated from human peripheral blood mononuclear cells, can be expanded in the lab while retaining their regulatory properties, making them a promising option for therapy in autoimmune diseases.

These CAR Tregs effectively suppress antibody production and B cell differentiation through a TGF-β-dependent mechanism, potentially reducing the risk of graft-versus-host disease compared to conventional CAR T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD. Imura, Y., Ando, M., Kondo, T., et al.[2021]

In a study involving five patients with severe systemic lupus erythematosus (SLE), treatment with CAR T cells targeting CD19 led to complete remission of the disease in all participants after 3 months, demonstrating high efficacy.

The CAR T cell therapy was well tolerated, with only mild side effects, and patients maintained drug-free remission for an average of 8 months, even after B cells reappeared, indicating a durable response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Mackensen, A., Müller, F., Mougiakakos, D., et al.[2023]

A new fusion protein, CD19sIg1-4, was developed to specifically detect anti-CD19 CAR expression in T-cells, showing effective binding in ELISA assays and enabling sensitive flow cytometry analysis.

This reagent can identify CAR-modified T-cells with high specificity and low background, allowing for better monitoring of CAR T-cell therapies targeting B-lineage malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CD19/Fc fusion protein for detection of anti-CD19 chimeric antigen receptors. De Oliveira, SN., Wang, J., Ryan, C., et al.[2021]

Adoptive T-cell therapy using anti-CD19 chimeric antigen receptor (CAR)-expressing T cells showed strong effectiveness in eliminating lymphoma cells in a murine model, with complete eradication of normal B cells lasting for at least 143 days after treatment.

The success of the anti-CD19-CAR-transduced T cells in fighting lymphoma was significantly enhanced by pre-treatment irradiation of the mice, and these CAR T cells outperformed the original anti-CD19 monoclonal antibody in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Kochenderfer, JN., Yu, Z., Frasheri, D., et al.[2023]

Anti-CD19 CAR T cell therapies have shown promise in treating aggressive B-cell lymphomas that are resistant to conventional therapies, achieving durable remissions in 33%-40% of patients with relapsed or refractory disease.

While these therapies can lead to significant side effects like cytokine release syndrome and neurologic toxicities, these are generally manageable and reversible, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapies for Aggressive B-Cell Lymphomas: Current and Future State of the Art. Abramson, JS., Lunning, M., Palomba, ML.[2021]

Anti-CD19 CAR T cell therapy has shown promising results in treating advanced-stage B-cell malignancies, with some patients achieving long-term remissions after treatment, indicating its potential as a new standard therapy.

While the therapy demonstrates strong efficacy by specifically targeting CD19, some patients have experienced acute adverse effects linked to increased inflammatory cytokines, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Kochenderfer, JN., Rosenberg, SA.[2021]

Allogeneic CD19 CAR T cells can effectively target lymphoma without significantly increasing the risk of graft-versus-host disease (GVHD), as shown in mouse models of allo-HSCT and lymphoma.

The study found that enhanced stimulation of alloreactive T cells with CD28-costimulated CD19 CARs leads to their clonal deletion and reduced effector function, which helps prevent GVHD while maintaining anti-lymphoma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. Ghosh, A., Smith, M., James, SE., et al.[2023]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3469.1/529281/A-Study-of-Kyv-101-a-CD19-CAR-T-Cell-Therapy-in

A Study of Kyv-101, a CD19 CAR T Cell Therapy, in ... We hypothesize that KYV-101, a fully human autologous CD19 CAR T-cell, will achieve CNS penetration in patients with progressive forms of MS.

2. thelancet.com thelancet.com/journals/lanrhe/article/PIIS2665-9913(24)00282-0/fulltext

CD19-targeting CAR T-cell therapy in patients with diffuse ... CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus.

3. kyvernatx.com kyvernatx.com/press-releases/fda-clearance-of-ind-for-kyv-101/

Kyverna Therapeutics Announces FDA Clearance of IND ... This is the third IND clearance for KYV-101, a novel, fully human CD19 CAR T-cell therapy designed for use in patients with B cell-driven autoimmune diseases.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06451159

NCT06451159 | A Study of KYV-101, a CD19 CAR T Cell ... The goal of this study is to test a drug called KYV-101 in people who have progressive multiple sclerosis (MS) and who have not responded to standard therapies ...

5. 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 demonstrated ...

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000212317

A Phase 1, Open-label, Single Center Study of KYV-101 ... We are conducting a Phase 1 prospective clinical trial assessing the feasibility and safety of treating subjects with progressive Multiple Sclerosis with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S3050708125000084

CD19-targeting CAR T cell therapy in five patients with ... The analysis of our 5 patients suggests that CD19-targeting CAR T cells are a feasible treatment option that can be used in patients who are ineligible for ...