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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety, tolerability, and clinical activity of KYV 101 (a fully-human anti-CD19 CAR T-cell therapy) in adult subjects with B cell-driven autoimmune diseases. The trial anticipates enrolling participants to reach a maximum of 24 participants who will receive 1 dose of KYV-101 and will be followed for 2 years.

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.

What data supports the idea that KYV-101 for Autoimmune Diseases (also known as: KYV-101, KYV-101, Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy) is an effective treatment?

The available research shows that KYV-101, a type of CAR T-cell therapy, is promising for treating autoimmune diseases. It has been effective in targeting and reducing harmful immune cells, like B cells, which are involved in these diseases. Studies have shown that this treatment can lead to positive outcomes in conditions like systemic lupus erythematosus and myasthenia gravis. Compared to traditional treatments that only manage symptoms, KYV-101 has the potential to be more effective by directly targeting the cells causing the disease. Additionally, it has shown success in preclinical models, suggesting it could be a more lasting solution than current therapies. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment KYV-101 for autoimmune diseases?

Research shows that similar treatments using CAR T cells, like KYV-101, have been successful in targeting and reducing harmful immune cells in autoimmune diseases. These treatments have shown promise in conditions like systemic lupus erythematosus and myasthenia gravis by eliminating problematic B cells and reducing autoantibody levels. ^{1 2 3 4 5}

What safety data is available for KYV-101 (Anti-CD19 CAR T-Cell Therapy)?

Safety data for KYV-101, also known as Anti-CD19 CAR T-Cell Therapy, includes reports of cardiovascular events such as arrhythmias, heart failure, and myocardial infarction, with a high mortality rate associated with these events. Other common adverse events include cytokine release syndrome, neurotoxicity, hematotoxicity, and complications like hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation. These adverse events are significant and can be fatal, highlighting the need for careful monitoring and management during treatment. ^{6 7 8 9 10}

What safety data exists for KYV-101 (Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy) in humans?

CAR T-cell therapy, including treatments like KYV-101, has been associated with several safety concerns. Common side effects include cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), which can be serious. Other potential risks include heart problems, blood disorders, and complications affecting various organs. ^{6 7 8 9 10}

Is KYV-101 a promising treatment for autoimmune diseases?

Yes, KYV-101, which is a type of CAR T-cell therapy, shows promise as a treatment for autoimmune diseases. It works by targeting and eliminating harmful immune cells that attack the body's own tissues. This approach has been successful in cancer treatment and is now being explored for autoimmune diseases, offering hope for more effective and potentially curative options. ^{1 3 4 11 12}

How is the treatment KYV-101 different from other treatments for autoimmune diseases?

KYV-101 is a unique treatment because it uses genetically engineered T cells, known as CAR-T cells, to specifically target and eliminate the immune cells that mistakenly attack the body's own tissues. Unlike traditional treatments that broadly suppress the immune system, this approach aims to be more precise and potentially curative by directly addressing the underlying cause of autoimmune diseases. ^{1 3 4 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

CAR T cells for treating autoimmune diseases. [2023]

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

CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD. [2021]

3. China pubmed.ncbi.nlm.nih.gov

CARs: a new approach for the treatment of autoimmune diseases. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Based Therapy as a Potential Approach in Autoimmune Diseases: How Close Are We to the Treatment? [2021]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Gene therapy strategies towards immune tolerance to treat the autoimmune diseases. [2019]

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

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. [2021]

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

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

12. Netherlands pubmed.ncbi.nlm.nih.gov

GITR+ regulatory T cells in the treatment of autoimmune diseases. [2022]