Tests a CAR-T cell treatment in adults with ANCA-positive vasculitis

Trial details

Who runs it

David Simon

Trial code

NCT06590545EU 2024-517303-36-00

Record updated

19 September 2024

Original description

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) immunoglobulin (IgG) positive ANCA associated vasculitis (AAV).Read full original descriptionShow less

Anti-CD 19 CAR-T Cell Therapy in Patients With ANCA Vasculitis: a Two-stage Interventional, Prospective, Open-label, Phase I/II Trial in Patients With Active, Treatment Refractory, ANCA-IgG-positive Vasculitis

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) immunoglobulin (IgG) positive ANCA associated vasculitis (AAV).

The main questions it aims to answer are:

* To assess the safety of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory, ANCA-IgG-positive AAV * To assess the clinical efficacy of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory ANCA-IgG-positive AAV * To assess the ANCA seroconversion rate in subjects with active, treatment refractory ANCA-IgG-positive AAV

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 visits at the site.

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: Prior treatment with anti-CD19 antibody therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR T cell therapy); 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; Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis,; Subjects participating in another clinical trial with an investigational medicinal product or medical device (3 months before this trial); Clinically relevant rapidly progressive glomerulonephritis or pulmonary alveolar hemorrhage; History of bone marrow/ hematopoietic stem cell or solid organ transplantation; Known hypersensitivity to any drug components; Malignancy in the last 5 years before screening (except adequately treated basal or squamous cell skin cancer); 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,; 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; 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; 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),; Pregnant or lactating females; Females who are intending to conceive during the study; 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,.

ClinicalTrials.gov NCT06590545 · EU CTIS 2024-517303-36-00