CAR T-Cell Therapy for Lupus Nephritis

Recruiting at 5 trial locations

Overseen By Kyverna Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Kyverna Therapeutics

Disqualifiers: Hepatitis, HIV, Stroke, Seizure, 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: Up to 52 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment that uses modified immune cells to target and destroy harmful cells in adults with severe kidney inflammation from lupus that doesn't respond to usual treatments.

Will I have to stop taking my current medications?

The trial information does not specify if 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 effectiveness of the treatment KYV-101, Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, for lupus nephritis?

Research shows that anti-CD19 CAR T-cell therapy has been effective in treating systemic lupus erythematosus (SLE), a related condition, by reducing disease activity and achieving remission in patients who did not respond to other treatments. This suggests potential effectiveness for lupus nephritis, which is a kidney-related complication of SLE. ^{1 2 3 4 5}

Is CAR T-Cell Therapy safe for humans?

CAR T-Cell Therapy targeting CD19 has been generally well tolerated in patients with systemic lupus erythematosus (SLE), with only mild side effects like cytokine-release syndrome (a mild immune reaction). Safety data from these studies suggest it is feasible and tolerable in humans. ^{1 2 3 6 7}

How is the treatment KYV-101 for lupus nephritis different from other treatments?

KYV-101, a CAR T-cell therapy, is unique because it uses modified immune cells to target and destroy specific B cells involved in lupus nephritis, potentially leading to long-term remission without ongoing medication. This approach differs from traditional treatments like corticosteroids and immunosuppressive drugs, which broadly suppress the immune system and often have significant side effects. ^{1 2 3 4 7}

Research Team

MD

Principal Investigator

Kyverna Therapeutics

Eligibility Criteria

This trial is for adults over 18 with a clinical diagnosis of Systemic Lupus Erythematosus (SLE) who meet specific criteria, including positive tests for certain autoantibodies and biopsy-proven proliferative lupus nephritis. Participants must be up to date on vaccinations, including COVID-19. Those with severe neurological disorders, active hepatitis B or C, HIV, primary immunodeficiency, significant heart disease or previous malignancies (with some exceptions), or prior cellular/gene therapy are excluded.

Inclusion Criteria

I have been diagnosed with lupus according to the 2019 EULAR/ACR criteria.

My kidney biopsy shows I have a severe type of inflammation.

I am up to date with all recommended vaccinations, including COVID-19.

Exclusion Criteria

You have a weakened immune system from birth.

I have previously received CAR-T or gene therapy.

I have severe kidney inflammation or serious brain-related lupus symptoms.

Timeline

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

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• KYV-101

Trial Overview The study is testing KYV-101 anti-CD19 CAR-T cell therapy in subjects with refractory lupus nephritis that hasn't responded to other treatments. It involves modifying the patient's T-cells to target CD19 protein on B cells implicated in SLE. The treatment follows a standard lymphodepletion regimen which prepares the body for receiving these modified T-cells.

Participant Groups

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+

Findings from Research

In a small study of five treatment-resistant patients with systemic lupus erythematosus (SLE), CD19 CAR T cell therapy led to significant clinical improvements and remission in all participants after 3 months, demonstrating its potential efficacy.

The treatment was well tolerated, with only mild cytokine release syndrome reported, suggesting a favorable safety profile for this innovative therapy in seriously ill SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. Boulougoura, A., Gendelman, H., Surmachevska, N., et al.[2023]

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]

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]

High-dose corticosteroids are the standard initial treatment for severe inflammation in lupus nephritis, but long-term management often requires additional therapies to address underlying immune system issues.

New treatment options for lupus nephritis include novel immunosuppressive agents and combination therapies, which may improve efficacy and reduce toxicity compared to traditional treatments like cyclophosphamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the treatment of proliferative lupus nephritis. Balow, JE., Austin, HA.[2019]

Current treatments for lupus nephritis, like corticosteroids and cyclophosphamide, are effective but come with significant side effects, highlighting the need for safer, targeted therapies.

New therapeutic strategies are being developed to specifically interrupt the disease process, such as blocking co-stimulatory molecules and targeting cytokines, which could lead to more effective and less toxic treatments for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel approaches in the treatment of lupus nephritis. Illei, GG., Czirják, L.[2019]

Complete and sustained depletion of CD19+ B cells using CD19-targeted CAR T cells was shown to be a highly effective therapy in lupus models, significantly reversing disease symptoms and extending lifespan in mouse models of lupus.

This approach demonstrated long-lasting effects, with CAR T cells remaining active for up to one year, suggesting that sustained B cell depletion could be a promising strategy for treating lupus in humans, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Kansal, R., Richardson, N., Neeli, I., et al.[2021]

In a study involving six patients with systemic lupus erythematosus (SLE), researchers successfully produced functional anti-CD19 CAR T cells from their T cells, demonstrating that leukapheresis can yield sufficient T-cell numbers for clinical-scale production despite the challenges posed by autoimmune conditions.

The generated CAR T cells exhibited high expansion rates, viability, and specific cytotoxicity against CD19+ cell lines in vitro, indicating that CAR T-cell therapy can be effectively developed for patients with autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus. Kretschmann, S., Völkl, S., Reimann, H., et al.[2023]

References

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

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. [2023]

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

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. [2023]

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

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Progress in the treatment of proliferative lupus nephritis. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Novel approaches in the treatment of lupus nephritis. [2019]

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

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. [2021]

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

Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus. [2023]