KYV-101 for Autoimmune Diseases

(CARTIMMUNE Trial)

Overseen By Emily Marcuson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: David Porter

Must be taking: Immunosuppressive therapies

Must not be taking: CAR T, Gene therapy

Disqualifiers: HIV, Hepatitis B, Stroke, 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: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of KYV-101 (Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy) for individuals with certain autoimmune diseases. The treatment uses a specific type of cell therapy to target the immune system. Participants will receive one dose and be monitored for two years to assess its effects. Individuals with lupus-related kidney issues, certain types of muscle inflammation, systemic sclerosis affecting the skin, or specific forms of vasculitis, who have not responded well to other treatments, may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants must have had an inadequate response or intolerance to certain treatments, suggesting that some medications might need to be adjusted. It's best to discuss your specific situation with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it mentions that participants should have had an inadequate response or intolerance to certain treatments, which might imply some changes to your medication regimen. It's best to discuss your specific situation with the trial coordinators.

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

Research has shown that KYV-101, a therapy using modified immune cells, has been safe in earlier studies. For people with lupus nephritis, the treatment was feasible and did not cause severe side effects, with some patients experiencing improvement. KYV-101 was also considered a potential treatment for systemic sclerosis. In another study on muscle inflammation, the treatment proved safe, improved symptoms, and did not cause serious side effects in the short term.

For ANCA-associated vasculitis, long-term safety data is not yet available, but some side effects, such as an overactive immune response, can occur. However, past studies have managed these effects. Since this trial is in Phase 1, the primary goal is to assess the treatment's safety. Researchers are closely monitoring how participants respond. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about KYV-101 because it offers a fresh approach to treating autoimmune diseases like SLE, DCSS, IIM, and AAV. Unlike standard treatments that focus on managing symptoms, KYV-101 is paired with lymphodepleting chemotherapy—using cyclophosphamide and fludarabine—to potentially reset the immune system. This combination targets the underlying causes by reducing harmful immune cells before introducing KYV-101, which may enhance the body's ability to regulate itself. The innovative mechanism could provide a more effective and long-lasting solution for patients who struggle with current therapies.

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

Research shows that KYV-101, a therapy using specially modified immune cells, holds promise for treating several autoimmune diseases affecting B cells. In this trial, participants with lupus nephritis will receive KYV-101, and small studies have found it both effective and manageable for this condition. For diffuse cutaneous systemic sclerosis, another group in this trial will receive KYV-101, and similar therapies have shown impressive results, suggesting KYV-101 might also be beneficial. Additionally, participants with idiopathic inflammatory myopathy and ANCA-associated vasculitis will receive KYV-101 in separate arms of this trial. Early research in these diseases indicates that KYV-101 may work by reducing harmful B cells. Although complete results are pending, these early findings offer hope that KYV-101 could effectively treat these serious autoimmune conditions. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with autoimmune diseases like inflammatory myopathies, systemic sclerosis, and lupus. Participants must have specific symptoms and test results that show active disease, such as muscle enzyme levels above normal or evidence of active myositis on MRI.

Inclusion Criteria

Your creatine kinase levels are four times higher than the normal upper limit.

I have been diagnosed with a type of inflammatory muscle disease.

I have been diagnosed with a specific type of muscle inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine for 3 days

1 week

Treatment

Participants receive a single dose of KYV-101 CAR T-cell therapy

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• KYV-101

Trial Overview The study tests KYV-101, a new CAR T-cell therapy targeting B cells in autoimmune diseases. It's given once to up to 24 people who are then monitored for two years. The trial also uses Cyclophosphamide and Fludarabine before the main treatment.

How Is the Trial Designed?

Group I: SLE Experimental Treatment 3 Interventions

Participants with SLE-related nephritis will receive will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

Group II: IIM Experimental Treatment 3 Interventions

Participants with idiopathic inflammatory myopathy will receive will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

Group III: DCSS Experimental Treatment 3 Interventions

Participants with diffuse cutaneous systemic sclerosis will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

Group IV: AAV Experimental Treatment 3 Interventions

Participants with ANCA-associated vasculitis will receive will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

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?

David Porter

Lead Sponsor

Trials

1

Recruited

20+

Kyverna Therapeutics

Industry Sponsor

Trials

11

Recruited

320+

Published Research Related to This Trial

Cell-based therapies using genetically engineered T cells, particularly CAR-T and CAAR-T cells, show promise in treating autoimmune diseases by targeting and destroying autoreactive immune cells.

Preclinical studies indicate that these therapies can effectively suppress autoimmune manifestations, but challenges such as identifying target autoantigens and ensuring safety and effectiveness must be addressed before clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Based Therapy as a Potential Approach in Autoimmune Diseases: How Close Are We to the Treatment? Sadeqi Nezhad, M., Seifalian, A., Bagheri, N., et al.[2021]

Autoimmune diseases affect nearly 5% of the global population, and current treatments primarily focus on reducing symptoms rather than curing the disease, highlighting the need for more targeted therapies.

Emerging strategies, such as using nanoparticles to deliver autoantigenic peptides and developing chimeric autoantibody receptor T cells, aim to specifically target autoreactive immune cells and restore self-tolerance, offering a promising direction for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologia Futura: Emerging antigen-specific therapies for autoimmune diseases. Sármay, G.[2021]

Therapies that promote the expansion of regulatory T cells (Tregs), particularly those targeting the GITR protein, could potentially provide a safe and effective curative treatment for autoimmune diseases, which currently lack such options.

Research indicates that GITR is crucial for both thymic and peripheral Treg expansion, and its presence in patients with milder autoimmune conditions suggests a possible therapeutic target for improving disease outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GITR+ regulatory T cells in the treatment of autoimmune diseases. Petrillo, MG., Ronchetti, S., Ricci, E., et al.[2022]

Adoptive transfer of engineered T cells, specifically CAR T cells, shows promise as a potential curative therapy for autoimmune disorders, with early clinical results indicating effectiveness in conditions like systemic lupus erythematosus and myasthenia gravis.

Innovative approaches, such as chimeric autoantibody receptor T cells, are being developed to target specific B cell clones responsible for autoantibody production, while regulatory CAR T cells aim to modulate rather than eliminate autoreactive immune cells, highlighting a nuanced strategy in treating autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells for treating autoimmune diseases. Blache, U., Tretbar, S., Koehl, U., et al.[2023]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

CAR T cell therapy, particularly with the approval of tisagenlecleucel, has shown remarkable efficacy in treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia, with six therapies approved as of April 2023 for B-cell malignancies and multiple myeloma.

However, the therapy is associated with significant adverse events like cytokine release syndrome, which are more severe with higher pretreatment tumor burdens; thus, initiating therapy early or using a debulking strategy may help mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. Mitra, A., Barua, A., Huang, L., et al.[2023]

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

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]

Autoimmune diseases like type 1 diabetes and multiple sclerosis affect about 6% of the population and currently have no cure, with treatments often involving toxic immunosuppressive therapies.

The study proposes a novel gene therapy approach using genetically modified haematopoietic stem cells to induce immune tolerance by expressing specific autoantigens in the thymus, potentially offering a long-term solution to prevent and cure autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy strategies towards immune tolerance to treat the autoimmune diseases. Siatskas, C., Chan, J., Field, J., et al.[2019]

Chimeric antigen receptor (CAR)-based therapies, originally developed for cancer treatment, are showing promise in treating autoimmune diseases by using CAR-T cells to target and deplete harmful immune cells, leading to favorable outcomes.

CAR-T regulatory T cells (Tregs) have potential in restoring immune tolerance in autoimmune diseases, and advancements in gene editing and synthetic biology are enhancing the effectiveness and safety of these CAR-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs: a new approach for the treatment of autoimmune diseases. Sun, Y., Yuan, Y., Zhang, B., et al.[2023]

In a review of 996 adverse events related to CAR T cell therapy from 2017 to 2019, 19.7% were cardiovascular events (CVEs), with arrhythmias being the most common, indicating a significant risk associated with this treatment.

Patients experiencing CVEs had a higher mortality rate of 30.1%, highlighting the need for careful monitoring for cardiovascular issues, especially in those also presenting with neurotoxicity or cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. Guha, A., Addison, D., Jain, P., et al.[2021]

A systematic analysis of CAR T-cell therapy adverse events revealed 5,112 reports of hematotoxicity, highlighting significant under-reporting of severe conditions like hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC), which have high mortality rates of 69.9% and 59.6%, respectively.

The study identified 23 hematologic adverse events that were significantly over-reported compared to the general database, emphasizing the need for increased awareness and monitoring of these rare but potentially fatal toxicities in CAR T therapy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. Song, Z., Tu, D., Tang, G., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06590545

Study Details | NCT06590545 | Anti-CD 19 CAR-T Cell ... This study aims to investigate the use of KYV101 (a fully human anti-CD19 CAR T cell therapy) in ANCA-IgG-positive AAV patients who are refractory to previous ...

2. renalandurologynews.com renalandurologynews.com/news/vasculitis-aav-safe-efficacy-anti-cd19-bcma-cart-therapy/

New Study Will Assess Safety, Efficacy of Anti-CD19/BCMA ... A new study will evaluate the safety and efficacy of universal allogeneic anti-CD19/BCMA CAR T-cells in relapsed or refractory autoimmune diseases.

3. ard.bmj.com ard.bmj.com/content/83/4/499

CD19-targeting CAR T cells protect from ANCA-induced acute ... We tested the hypothesis that CAR T cells targeting CD19 deplete B cells, including MPO-ANCA-producing B cells, thereby protecting from ANCA-induced NCGN.

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/536955

Anti-CD 19 CAR-T Cell Therapy in Patients with ANCA ... Participants will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR-T cell immunotherapy. Follow-up time is 52 weeks with regular ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07161193

NCT07161193 | Anti-CD19 Chimeric Antigen Receptor T ... The primary objective is to evaluate the safety and efficacy of CD19 CAR T cell therapy in subjects with Refractory Autoimmune Diseases and to ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06702

Autologous Fully-Human Anti-CD19 Chimeric Antigen ... This phase I trial studies the safety and side effects of autologous fully-human anti-CD19 chimeric antigen receptor T-cell (KYV-101) and to see how well it ...