An Open-label Phase I/II Safety and Feasibility Basket Study of UKT-CART19.1

An open-label phase I/II, single-center, interventional single-arm basket trial of UKT-CART19.1 in patients with relapsed/refractory autoimmune diseases

Inclusion Criteria: 1. Patients at least 18 years of age, and ≤ 80 years old at the time of signing the informed consent 2. Signed and dated informed consent by participants before conduct of any trial-specific procedure 3. One of the following diseases according to the EULAR/ACR criteria (see appendices) for IIM/AAV/RA/SSc; McDonald criteria Wingerchuk et al., 2015; KKNMS; Sechi et al., 2022 for MS or clinical standards for PV and ITP plus disease active according to the specific disease as follows: * Idiopathic inflammatory myositis (IIM): Disease activity defined by CK \> 3x ULN and clinical symptoms and / or disease activity documented by MRI * ANCA associated vasculitis (AAV): Disease activity defined as BVAS-3 new/worse \> 6, i.e. ongoing or new organ damage (lung, kidney or CNS) * Rheumatoid Arthritis (RA): Disease activity defined DAS28 \> 4 * Pemphigus vulgaris (PV): Disease activity defined by PDAI \>15 points * Multiple sclerosis (MS): clinical activity previous 24 months: greater than or equal to 1 relapse with or without increase of EDSS, clinical progression previous 24 months: increase of EDSS 1 or increase in other MS-related measures (such as 25FWT, 9HPT, SDMT), MRI activity previous 24 months: greater than or equal to 1 Gd+ lesion or new or new enlarging T2-hyperintense lesion greater than or equal to 3 mm, failure of greater than or equal to 2 high efficacy therapy (not included in AHCST criteria) * Immune thrombocytopenic purpura (ITP): Disease activity defined as thrombocytes \10% and/or decline of DLCO \>15% (of predicted values) and/or new organ involvement (heart, kidney) AND refractory to at least (but not limited) to 2 immunosuppressive disease-specific standard treatment: * IIM: greater than or equal to 2 standard treatments in accordance with the current AWMF S2k Guideline (S2kLeitlinie Myositissyndrome. Version: 6.0 Stand: 28.04.2022 Gültig bis: 27.04.2027) * AAV: greater than or equal to 2 standard treatments in accordance with EULAR recommendations (Hellmich B et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764. PMID: 36927642. * RA: greater than or equal to 4 standard treatments in accordance with the current EULAR Recommendations for the Management of RA (Smolen J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update Annals of the Rheumatic Diseases, 2026; 85, 991-1009) * PV: greater than or equal to 2 standard treatments in accordance with the current S2k Guideline (S2k-Leitlinie Diagnostik und Therapie des Pemphigus vulgaris / foliaceus und des bullösen Pemphigoids. Version: 3.0 Stand: 01.04.2026 Gültig bis: 31.03.2031). * MS: greater than or equal to 2 high efficacy therapy ("Wirksamkeitskategorie 3") in accordance with the current S2k Guideline (Hemmer B. et al., Diagnose und Therapie der Multiplen Sklerose, Neuromyelitis-optica-Spektrum-Erkrankung (NMOSD) und MOG-IgG-assoziierten Erkrankung (MOGAD), S2k-Leitlinie, 2026, in: Deutsche Gesellschaft für Neurologie (Hrsg.), Leitlinien für Diagnostik und Therapie in der Neurologie. Online: www.dgn.org/leitlinien (abgerufen am 15.06.2026) * ITP: failure of at least Glucocorticoids, Thrombopoetin receptor agonists (TPO-RA) and Fostamatinib in accordance with the current Onkopedia Guideline (DGHO Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e. V. (Hrsg.): Immunthrombozytopenie (ITP). Onkopedia Leitlinie. Stand: August 2024. https://www.onkopedia.com/de/onkopedia/guidelines/immunthrombozytopenie-itp (Abgerufen am: 15.06.2026)) * SSc: greater than or equal to 2 standard of care systemic treatment in accordance with the current EULAR Recommendations ( Del Galdo F et alEULAR recommendations for the treatment of systemic sclerosis: 2023 update Annals of the Rheumatic Diseases Published Online First: 11 October 2024. doi: 10.1136/ard-2024-226430) 4. Male participants able to father children and female participants of childbearing potential must practice true abstinence or agree to use 2 highly effective methods (i.e. those that result in a low failure rate (i.e., \< 1% per year) of contraception throughout the duration of the study. Male fertile subjects must also not donate sperm during the study and for at least 12 months following the UKT-CART19.1 infusion 5. Female Subject of childbearing potential and male subjects with female partner of childbearing potential is willing to use highly effective contraceptive methods during treatment until 12 months after IMP exposure. For the purpose of this document, a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm apostmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. For the purpose of this document, a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Highly effective methods are defined as those that result in a low failure rate (ie, less than 1% per year) when used consistently and correctly. The following are highly effective methods of contraception: * combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1: - oral - intravaginal - transdermal * progestogen-only hormonal contraception associated with inhibition of ovulation1: * oral * injectable * implantable2 * intrauterine device (IUD) 2 * intrauterine hormone-releasing system (IUS)2 * bilateral tubal occlusion2 * vasectomised partner2,3 * sexual abstinence4 1. Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the contraception method. 2. Contraception methods that in the context of this guidance are considered to have low user dependency. 3. Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success. 4. In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Woman of childbearing potential (WOCBP) must also: - Have a negative pregnancy test as verified by the Investigator, one negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test result at screening, prior to LD. This applies even if the subject practices true abstinence from heterosexual contact. - Perform pregnancy testing every month for 6 months after IMP administration. A home test is sufficient. * Agree to abstain from breastfeeding during study participation and for at least 12 months after IMP administration. 6. All subjects must agree to refrain from donating blood while on study drug and for 1 year after discontinuation from this study treatment. 7. Absolute CD3+ T cell count ≥100/μl at time of leukapheresis 8. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 9. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 neuropathy 10. Subject must have adequate vascular access for leukapheresis 11. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted 12. Subject is willing and able to adhere to the study visit schedule and other protocol requirements as well as agrees to continued follow up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials Exclusion Criteria: 1. Subject used any investigational agents within 15 days of leukapheresis 2. Contraindications to the IMP and its components, including but not limited to hypersensitivity to the CAR-T cell product, excipients, lymphodepleting agents and/or tocilizumab. 3. Subject received any of the following within the last 7 days of leukapheresis: Major surgery (as defined by the investigator) Radiation therapy Use of any systemic anti-neoplastic drug therapy 4. Patients who have previously received gene therapy 5. History or presence of clinically relevant CNS pathology other than the underlying diseases in this protocol, such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. 6. Subject has any of the following laboratory abnormalities: Absolute lymphocyte count \ 3 × upper limit of normal (ULN), non-Myositis related Serum total bilirubin \> 3.0 mg/dL for subjects with documented Gilbert's syndrome 7. Echocardiography (ECHO) or MRI with left ventricular ejection fraction \< 40% 8. Subject with a history of Class III or IV congestive heart failure (CHF) 9. Subject with a history of myocardial infarction within the last 12 months 10. Patients unable to stop immunosuppressive treatment prior to leukapheresis (AZA, TAC, MMF, CYC, mitoxantrone, JAK inhibitors, or GC at prednisolone equivalent dose \>10mg/day). Intermittent topical, inhaled or intranasal corticosteroids are allowed 11. Subject is positive for human immunodeficiency virus (HIV-1), uncontrolled hepatitis B or C 12. Subject with FVC \