Phase 1 Study of HBI0101 CAR-T in Refractory B-Cell Autoimmune Diseases

Treatment tested

• HBI0101 CART

Other measures (10)

Inclusion Criteria: 1. Age: 18\~80 years old; for patients aged ≥ 75 years, geriatric assessment and endorsement are required; 2. Diagnosis of B-cell mediated ARDs listed below: SLE patients: individuals diagnosed with SLE according to American College of Rheumatology (ACR) and/or Systemic lupus international collaborating clinics (SLICC) classification criteria, who have severe and progressive disease course reflected by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score of 8 or more. Eligible patients must have failed to at least one of the conventional DMARDs (azathioprine, methotrexate, mycophenolate mofetil or cyclophosphamide), one of the calcineurin inhibitors (tacrolimus or cyclosporin) and one of the biologic agents (belimumab, rituximab or aniflorumab), each administered for a minimum of 3 months, or have a contraindication to, or have experienced toxicity from, any therapy within these categories. The failure is defined as: * lack of response per SLEDAI-2k (\<4 points reduction from baseline) or no improvement in BILAG domains, or * disease flare per SLEDAI-2k (≥4 points increase from baseline) or new BILAG A or ≥2 new BILAG B organ scores, or intolerance or discontinuation due to adverse effects. SSc patients: Patients who were diagnosed with diffuse or limited cutaneous SSc according to the College of Rheumatology/European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria, with severe or rapidly progressive disease Eligible patients must meet any of the following criteria: * Progression of skin thickening ≥ 12 over the past 6 months or Modified Rodnan skin score (mRSS) ≥15 * Any Medsger Disease Severity Score grade 3-4 in one major organ or grade ≥2 in two organs * Progressive interstitial lung disease evidenced by HRCT or FVC \<80% or DLCO \<80%, or evidence of pulmonary function decline, defined as an absolute FVC decline of ≥ 10% , or FVC decline of 5% -9% combined with DLCO 15%. * Other internal organ involvement. Eligible patients must have failed to at least two state-of-the-art immunosuppressive therapies including MTX, MMF, cyclophosphamide, azathioprine, nintedanib, tocilizumab or rituximab; each therapy must have been administered for a minimum of 3 months, unless discontinued due to a contraindication or toxicity. The failure is defined as: * lack of response in skin per mRSS (≤20% relative and ≤5 point absolute reduction from baseline) or no clinically meaningful improvement in FVC, DLCO, or other organ involved assessed by Medsger DSS, or * disease flare in skin per mRSS (increase in mRSS ≥20% and ≥5 points from baseline) or decline in FVC ≥10% predicted or in DLCO ≥15% predicted from baseline, other major SSc complication, or * intolerance or discontinuation due to adverse effects IIM, including dermatomyositis, anti-synthetase syndrome, immune mediated necrotizing myopathy, and polymyositis: patients must be diagnosed with IIM according to the 2017 ACR/EULAR Classification Criteria for idiopathic inflammatory myopathies. Eligible patients must have active disease, defined by at least one of the following: * CPK ≥4xULN * Loss of muscle strength in the weakest muscle group for less than 80% per MMT8 * Evidence on MRI of active myositis within last 6 months * Evidence on EMG of active myositis within last 6 months * Muscle biopsy evidence of active myositis within last 6 months Only patients with refractory disease will be recruited, defined as previous failure to (1) at least two of five non-glucocorticoids immunosuppressive therapies and (2) either rituximab or IVIG, each administered for a minimum of 3 months, or have a contraindication to, or have experienced toxicity from, any therapy within these categories. The five non-glucocorticoids therapies considered are azathioprine, MTX, MMF, IVIG, and rituximab The failure is defined as: * lack of response in muscle strength per MMT-8 or CPK (\<20% relative improvement) or per MRI or * disease flare in muscle strength per MMT-8 (≥30% decline) or CPK (≥30% rise) or objective worsening of other organ involvement per Myositis Disease Activity Assessment Tool or * intolerance or discontinuation due to adverse effects RA patients: Seropositive RA patients (positive for anti-cyclic citrullinated peptide and rheumatoid factor), diagnosed according to the 2010 ACR/EULAR classification criteria. Eligible patients must exhibit high disease activity (DAS28CRP ≥5.1), and be resistant to at least four conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARD) groups. Each patient must have previously received at least one medication from each of the mentioned groups, including * JAK-STAT inhibitors * Anti-TNF agents * Anti-IL6 drugs * Anti-CTLA4-Ig treatments, each administered for a minimum of 3 months, or have a contraindication to, or have experienced toxicity from, any therapy within these categories Drug resistance is defined as: * Inadequate clinical response measured by composite score DAS28CRP (> 3.6) or failure to reach ACR20 or * Disease progression measured by DAS28CRP (≥20% increase) or radiographic progression or * Intolerance or discontinuation due to adverse effects NMOSD: Patients must be diagnosis of AQP4-IgG-positive NMOSD based on the 2015 International Panel for NMOSD Diagnosis (IPND) criteria (Wingerchuk et al., 2015). Eligible patients must have experienced at least two relapses in the past 24 months, with at least one occurring in the preceding 12 months before screening Each patients must have previously received with inadequate disease control (one or more clinical attacks, with new MRI activity, despite adequate treatment dosing) at least one immunosuppressant for at least 6 months (azathioprine or mycophenolate mofetil) and/or Rituximab for at least 3 months and/or a targeted therapy (eculizumab, inebilizumab, or satralizumab) or must have a contraindication to such treatment. MS patients: must have confirmed history of diagnosis of primary progressive or secondary progressive MS . Eligible patients must have: Expanded Disability Status Scale (EDSS) score between 3.0 and 8.5 and evidence of disease activity, defined by either clinical progression and/or radiological finding on MRI, such as new, enhancing or enlarging lesions in the last 12 months. Eligible patient must have previously received at least one high efficacy drug and have been offered standard treatments and have experienced disease progression or lack of efficacy despite at least six months of treatment. These will include clinical activity (new relapse[s]), radiological activity (new or enlarging T2 lesions and/or gadolinium-enhancing lesions on MRI), or confirmed disability progression (an increase in least 1 point on the EDSS sustained for ≥6 months). Eligible patient must have history of treatment with anti-CD20 mAb with continuing evidence of worsening physical disability over a period of ≥6 months, with documented clinical disability progression within the year prior to inclusion, irrespective to concurrent MRI activity. MG patients must meet all the following criteria: - Confirmed diagnosis of generalized MG, supported by positive autoantibodies (anti-AChR, anti-MuSK). Disease Severity: * Myasthenia Gravis Activities of Daily Living (MG-ADL) score of ≥6, with ocular symptoms constituting less than 50% of the total score. * Myasthenia Gravis Foundation of America (MGFA) clinical classification of II to IV. Eligible patients must have Refractory Status and meet at least one of the following criteria: * No improvement or worsening myasthenic symptoms, with failure to achieve minimal manifestation status or meaningful improvement in MGFA class or MG-ADL score, or recurrent myasthenic exacerbations despite adequate immunosuppressive or immunomodulatory therapy

A Phase 1 study of HBI0101 BCMA-CART in B-Cell Mediated Autoimmune Rheumatic Diseases. The goal of the study is evaluation of safety and identification of the maximum HBI0101 CART dose that may be administered safely to patients with B-cell mediated autoimmune disease.