What side effects are associated with this type of intervention?

Common treatments for Lupus Nephritis, such as cyclophosphamide, mycophenolate mofetil, and rituximab, often have side effects including increased risk of infections, gastrointestinal symptoms (nausea, vomiting, diarrhea), bone marrow suppression leading to anemia or leukopenia, and potential liver toxicity. Rituximab, a B cell-depleting agent, can also cause infusion reactions, including fever, chills, and hypotension. Anti-CD19 CAR T cell therapy, which similarly targets B cells, may have side effects like cytokine release syndrome (fever, hypotension, respiratory distress) and neurotoxicity (confusion, seizures). Close monitoring and supportive care are essential to manage these adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Lupus Nephritis, focusing primarily on immunosuppressive therapies. One notable approval is Belimumab (Benlysta), a monoclonal antibody that inhibits B-cell activating factor (BAFF), thereby reducing the activity of B cells, which are implicated in the autoimmune response in lupus. While not directly targeting CD19, Belimumab's mechanism of reducing B cell activity is somewhat related to the approach of Anti-CD19 CAR T-cell therapy. Other treatments include corticosteroids and immunosuppressive drugs like mycophenolate mofetil and cyclophosphamide, which broadly suppress the immune system to control lupus activity.

What other types of research exist?

Promising novel alternatives to Anti-CD19 CAR T Cell Therapy for Lupus Nephritis patients include: 1) Belimumab, a monoclonal antibody that inhibits B-cell activating factor (BAFF), which has shown efficacy in systemic lupus erythematosus (SLE). 2) Rituximab, an anti-CD20 monoclonal antibody, which targets B cells and has been used in various autoimmune conditions. 3) Voclosporin, a calcineurin inhibitor recently approved for lupus nephritis, which helps reduce proteinuria and improve kidney function. 4) Anifrolumab, an anti-interferon receptor monoclonal antibody, which targets the type I interferon pathway implicated in SLE pathogenesis.

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CAR T-cell Therapy

CAR T-Cell Therapy for Lupus Nephritis

Phase 1 & 2

Recruiting

Research Sponsored by Kyverna Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Clinical diagnosis of SLE according to 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria

Biopsy-proven proliferative LN Class III or IV according to 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria

Must not have

Prior treatment with cellular therapy (CAR-T) or gene therapy product directed at any target

Rapidly progressive glomerulonephritis; history of or currently active severe central nervous system (CNS) lupus, including cerebritis, cerebrovascular accident, and seizures

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include immune system reactions like cytokine release syndrome (flu-like symptoms), neurologic toxicities such as confusion or seizures, infusion-related reactions, increased risk of infections due to immune suppression from lymphodepletion and CAR-T therapy itself.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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I have tested positive for specific autoimmune markers.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have previously received CAR-T or gene therapy.

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

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I have heart problems that affect my daily activities.

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I have had my spleen removed.

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I have had a stem cell transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

To Evaluate efficacy (Phase 2)

Secondary study objectives

To assess PRO after infusion of KYV-101 (Phase 1 and Phase 2)

To characterize the pharmacodynamics (PD) (Phase 1 and Phase 2)

To characterize the pharmacokinetics (PK) (Phase 1 and Phase 2)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2)Experimental Treatment2 Interventions

Recommended Phase 2 Dose

Group II: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1)Experimental Treatment2 Interventions

Dosing with KYV-101 CAR T cells

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Lupus Nephritis include immunosuppressive therapies such as corticosteroids, cyclophosphamide, and mycophenolate mofetil, which work by reducing the activity of the immune system to prevent further kidney damage. Novel treatments like Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy specifically target B cells by engineering T cells to recognize and destroy CD19-expressing B cells, which are responsible for producing autoantibodies that attack the kidneys. This targeted approach is significant for Lupus Nephritis patients as it aims to reduce the autoimmune response more precisely, potentially leading to better outcomes with fewer side effects compared to broad immunosuppression.

[Depletion of plasma cells - a novel strategy in the therapy of systemic lupus erythematosus in mice and man].