Status:

NOT_YET_RECRUITING

Anti-CD 19 CAR-T Cell Therapy in Patients with ANCA Vasculitis

Lead Sponsor:

David Simon

Collaborating Sponsors:

Kyverna Therapeutics

Conditions:

ANCA-IgG-positive ANCA Associated Vasculitis

Eligibility:

All Genders

18-75 years

Phase:

PHASE1

PHASE2

Brief Summary

The goal of this phase I/II clinical trial is to investigate anti-CD 19 chimeric antigen receptor T cell (CAR-T cell) therapy in patients with antineutrophil cytoplasmic antibodies (ANCA) immunoglobul...

Detailed Description

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 treatments. This study is designed to det...

Eligibility Criteria

Inclusion

  • Understand and voluntarily sign an informed consent form
  • Male or female, age ≥ 18 and ≤ 75 years at ti me of consent
  • Able to adhere to the study visits and protocol
  • Fulfilment of
  • EITHER both of the following
  • 2022 ACR-EULAR classification criteria for granulomatosis with polyangiitis (GPA)
  • detectable anti-PR3 antibodies (≥ 20 AU/ml in CLIA) at screening
  • OR both of the following
  • 2022 ACR/EULAR classification criteria for microscopic polyangiitis (MPA)
  • detectable anti-MPO antibodies (≥ 10 AU/ml in CLIA) at screening
  • Active disease, defined as Clinical activity (BVAS ≥ 3) at screening
  • Insufficient response or intolerance/contraindication to glucocorticoids and to at least one of the following treatments: rituximab, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, avacopan. Insufficient response is defined as having disease activity based on the definition explained in the previous bullet point
  • Male subjects unless surgically sterile, must agree to use two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child starting from the time of signing the Informed Consent Form (ICF) until 12 months after dosing of the IMP
  • Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening and must agree to use a highly effective contraceptive method (Pearl index less than 1) starting from the time of signing the ICF and for 12 months after dosing of the IMP
  • Updated vaccination record according to the STIKO recommendations for immuno-compromised patients

Exclusion

  • ANC less than 500/µl, ALC less than 100/µl or hemoglobin less than 8g/dl, absolute CD3+T cell count less than 100/µl at screening
  • Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh C), or heart or pulmonary (NYHA IV, blood oxygenation less than 92%) function
  • Clinically relevant rapidly progressive glomerulonephritis or pulmonary alveolar hemorrhage
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Prior treatment with anti-CD19 antibody therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR T cell therapy)
  • History of bone marrow/ hematopoietic stem cell or solid organ transplantation
  • Any concomitant severe active infection, e.g. HIV, hepatitis B or C, SARS-CoV-2 (COVID-19), or active tuberculosis as defined by a positive Quantiferon TB-test. If presence of latent tuberculosis is established then treatment according to local guide-lines must have been initiated prior to enrollment
  • Pregnant or lactating females
  • Females who are intending to conceive during the study
  • Known hypersensitivity to any drug components
  • Malignancy in the last 5 years before screening (except adequately treated basal or squamous cell skin cancer)
  • Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis,
  • Subjects who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (accord-ing to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG),
  • Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may increase the risks associated with study participa-tion or study agent administration, or may interfere with interpretation of results,
  • Subjects who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g. family members).
  • Subjects who are institutionalized by order of court or public authority,
  • Subjects participating in another clinical trial with an investigational medicinal product or medical device (3 months before this trial).

Key Trial Info

Start Date :

January 1 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

July 1 2027

Estimated Enrollment :

8 Patients enrolled

Trial Details

Trial ID

NCT06590545

Start Date

January 1 2025

End Date

July 1 2027

Last Update

September 19 2024

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