YTB323 for Lupus

Recruiting in Palo Alto (17 mi)

+14 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Infections, Uncontrolled diabetes, Malignancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The study is intended to assess safety, efficacy and cellular kinetics of YTB323 treatment in participants with severe refractory systemic lupus erythematosus.

Do I need to stop my current medications for the YTB323 trial?

The trial protocol does not specify if you need to stop your current medications, but it mentions an 'immunosuppressive washout' period, which suggests you might need to stop certain medications. It's best to discuss this with the trial team.

What data supports the effectiveness of the treatment YTB323 for Lupus?

Research shows that a similar treatment, anti-CD19 CAR T cell therapy, was highly effective in patients with lupus, leading to remission and improvement in symptoms. This therapy works by targeting and depleting B cells, which are involved in the disease process. ^{1 2 3 4 5}

What safety data exists for YTB323 (Rapcabtagene autoleucel) in humans?

The safety of CAR T-cell therapies, like YTB323, often involves risks such as cytokine release syndrome (a severe immune reaction), neurological side effects, infections, fever, diarrhea, nausea, low blood pressure, and fatigue. These side effects have been observed in similar therapies, such as Yescarta and Kymriah, which are also anti-CD19 CAR T-cell treatments. ^{6 7 8 9 10}

How is the YTB323 treatment different from other lupus treatments?

YTB323 is a unique treatment for lupus because it uses CAR T-cell therapy, which involves modifying a patient's own immune cells to target and destroy specific B cells that contribute to the disease. This approach is different from traditional lupus treatments, which often involve general immunosuppressive drugs, as it offers a more targeted and potentially long-lasting effect. ^{2 5 11 12 13}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceutical

Eligibility Criteria

This trial is for adults aged 18-65 with severe, treatment-resistant systemic lupus erythematosus (SLE). Participants must meet specific SLE criteria and have certain autoantibodies. They should have tried at least two immunosuppressive therapies without success and may also have kidney, heart, lung or blood vessel involvement. Major organ functions need to be adequate.

Inclusion Criteria

Signed informed consent

My kidney, liver, heart, blood, and lung functions are all within normal ranges.

I am between 18 and 65 years old and have been diagnosed with SLE according to the 2019 EULAR/ACR criteria.

Exclusion Criteria

Any psychiatric condition or disability making compliance with treatment or informed consent impossible

My condition is B cell aplasia.

I do not have any serious or recurring infections.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of YTB323

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Regular visits (in-person and virtual) for monitoring

Long-term safety follow-up

Long term safety follow-up to monitor adverse events and efficacy

Up to 2 years

Treatment Details

Interventions

• YTB323 (Other)

Trial Overview The study tests YTB323's safety, effectiveness, and how it affects immune cells in patients with severe refractory SLE. It aims to see if this new treatment can help where others failed.

Participant Groups

Group I: YTB323 Experimental Treatment 1 Intervention

Single infusion of YTB323

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

WA Uni School Of Med WUSCM Saint Louis, MO

Division of Rheumatology Immunology Birmingham, AL

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2963

Patients Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T therapy extends its reach to autoimmune diseases. Baker, DJ., June, CH.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slamming the brakes on lupus with CAR T cells. Clark, RA.[2019]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. Shah, BD., Ghobadi, A., Oluwole, OO., et al.[2023]

Yescarta (axicabtagene ciloleucel) is an engineered T-cell therapy that showed a 66% overall response rate and a 47% complete response rate in treating relapsed or refractory diffuse large B-cell lymphoma, based on a phase II study with a median follow-up of 15.1 months.

The therapy was associated with manageable adverse events, including cytokine release syndrome and neurological issues, making it a promising option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. Papadouli, I., Mueller-Berghaus, J., Beuneu, C., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise of CAR T-cell therapy in aggressive B-cell lymphoma. Nair, R., Neelapu, SS.[2021]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Jin, X., Xu, Q., Pu, C., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The variation of T-cell clonal repertoire in patients with systemic lupus erythematosus (SLE) following autologous peripheral blood hematopoietic stem cell transplantation]. Fu, YW., Zhu, P., Zhao, XW., et al.[2006]

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

CAR T therapy extends its reach to autoimmune diseases. [2023]

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

Slamming the brakes on lupus with CAR T cells. [2019]

4. 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]

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

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

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

CAR T Cell Toxicity: Current Management and Future Directions. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The promise of CAR T-cell therapy in aggressive B-cell lymphoma. [2021]

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

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

12. China pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. [2022]

13. China pubmed.ncbi.nlm.nih.gov

[The variation of T-cell clonal repertoire in patients with systemic lupus erythematosus (SLE) following autologous peripheral blood hematopoietic stem cell transplantation]. [2006]