CAR T-Cell Therapy for Lupus Nephritis

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called KYV-101 for individuals with lupus nephritis, a serious kidney condition linked to lupus. The goal is to assess the effectiveness of CAR T-cell therapy, which uses modified immune cells, in helping those who have not responded to other treatments. Participants must have a confirmed diagnosis of lupus nephritis with kidney involvement. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that KYV-101 is likely to be safe for humans?

Previous studies have shown KYV-101 to be safe. Research indicates that this treatment, a type of CAR T-cell therapy (where a patient's immune cells are modified to target specific cells), is well-tolerated. Reports from patients with lupus nephritis (a kidney condition) demonstrate that it can reduce B cells, which are part of the immune system. This reduction helps reset the immune system and stabilize kidney function.

Data from these studies indicate that patients did not experience major safety issues within 28 days after receiving the treatment. Thus, KYV-101 is considered safe so far. However, ongoing research aims to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for lupus nephritis, which often include immunosuppressive drugs like corticosteroids and cyclophosphamide, KYV-101 uses CAR T-cell therapy. This approach is unique because it involves reprogramming a patient’s own immune cells to specifically target and eliminate the problematic B cells that drive lupus. Researchers are excited about KYV-101 because it offers a targeted mechanism of action, potentially leading to more effective and longer-lasting remission with fewer side effects compared to traditional therapies. This innovative treatment could transform how lupus nephritis is managed by providing a more precise and personalized therapy option.

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

Research shows that KYV-101, a therapy using modified immune cells, may help treat lupus nephritis. Early studies revealed a significant drop in B cells, which can mistakenly attack the body in diseases like lupus. This treatment appears to reset the immune system and maintain kidney function, crucial for those with lupus nephritis. Initial trials found the therapy to be safe and manageable. These findings suggest KYV-101 could be a valuable option for this challenging condition. Participants in this trial will receive KYV-101 CAR-T cells with lymphodepletion conditioning in either Phase 1 or Phase 2 to further evaluate its effectiveness and safety. ^{2 3 4 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Kyverna Therapeutics

Are You a Good Fit for This Trial?

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 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

Up to 52 weeks

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 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.

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

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]

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 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]

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]

Citations

1.

kyvernatx.com

kyvernatx.com/press-releases/kyverna-therapeutics-to-present-new-data-of-kyv-101/

Kyverna Therapeutics to Present New Data of KYV-101 ...

KYV-101 is a novel, fully human CD19 CAR T-cell therapy for use in B cell-driven autoimmune diseases such as lupus nephritis, a serious complication of lupus.

2.

lupus.bmj.com

lupus.bmj.com/content/11/Suppl_1/A109

P95 First two US patients with lupus nephritis (LN) treated ...

KYV-101 is a fully human autologous anti-CD19 CAR T-cell therapy designed and demonstrated to have a favorable safety profile.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05938725?cond=Lupus%20Erythematosus,%20Systemic&term=CAR-T%20Cell%20Therapy&rank=6

NCT05938725 | KYSA-1: A Study of Anti-CD19 Chimeric ...

KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with refractory lupus nephritis. Official Title. KYSA-1: A Phase 1/2 ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10642250/

Journal Club: Anti‐CD19 Chimeric Antigen Receptor T Cell ...

These data suggest that CD19 CAR‐T cell therapy was feasible, tolerable, and effective in this small case series of refractory SLE. Nevertheless ...

5.

ir.kyvernatx.com

ir.kyvernatx.com/news-releases/news-release-details/kyverna-therapeutics-announces-new-patient-data-highlighting

Kyverna Therapeutics Announces New Patient Data ...

The data reinforce that treatment with KYV-101 drives deep B cell depletion in patients with LN, and appears to reset the immune system, stabilize eGFR, ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05938725

KYSA-1: 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 refractory lupus nephritis. Official Title. KYSA-1: A Phase 1/2 ...

7.

kyvernatx.com

kyvernatx.com/press-releases/kyverna-therapeutics-announces-achievement-of-28-day-post-infusion-milestone-for-first-u-s-patient-dosed-in-phase-1-clinical-trial-of-cd19-car-t-cell-therapy-for-lupus-nephritis/

KYV-101 is a novel, fully human CD19 CAR T-cell therapy ...

28-day post-infusion data support KYV-101 safety profile. KYV-101 is a novel, fully human CD19 CAR T-cell therapy designed for use in patients with B cell- ...