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

Recruiting now · Phase 1

Conditions studied: Systemic Sclerosis (SSc), Idiopathic Inflammatory Myopathy (IIM), Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS) Primary Progressive, Multiple Sclerosis (MS) Secondary Progressive, Neuromyelitis Optica Spectrum Disorder (NMOSD), Myasthenia Gravis (MG), Antiphospholipid Antibody Syndrome

In brief

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.

Key facts

Study ID

NCT07085676

Run by

Polina Stepensky

People needed

120

Starts

2024-09-01

Expected to finish

2030-11-01

Last updated by the study team

2026-05-06

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age: 18\~80 years old; for patients aged ≥ 75 years, geriatric assessment and endorsement are required;
• 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

You may not qualify if…

• CNS disease- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-autoimmune progressive neurologic condition or PML
• Abnormal liver function: aspartate transaminase (AST) or alanine transaminase (ALT) or glutamyl transpeptidase (GGT) or alkaline phosphatase (ALP) detection value is greater than 5 times the upper limit of normal (ULN); or total bilirubin test value greater than 3 times the upper limit of normal (ULN); Exceptional: liver function disturbance due to myositis.
• Cardiovascular disease: Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to leukapheresis/ moderate- severe pulmonary hypertension/ severe arrhythmia (ventricular tachycardia, ventricular fibrillation, high grade ventricular block) in the past 6 months; New York heart function class (NYHA) class III- Level IV or LVEF<45%.
• Lung disease: patients with chronic lung disease with any of the following: * Oxygen saturation (SpO2) < 90% on room air * FVC≤45% of predicted or DLCO≤40% of predicted at screening. * Evidence of pulmonary hypertension as defined as estimated RVSP> 50 mmHg.
• Muscle disease: evidence of any of the following: * Severe proximal muscle atrophy of upper or lower extremity on MRI or clinical examination. *Finding of muscular inflammation or myopathy other than the indication, such as inclusion body myositis (IBM), or cancer-associated myositis (myositis diagnosed within 2 years of cancer).
• Other uncontrolled diseases: acute diseases (such as acute pneumonia or other infection, pulmonary embolism, diabetic ketoacidosis, acute pancreatitis, etc.) that are clinically unstable or have not been effectively controlled and are not related to indicated autoimmune diseases which in the judgment of the investigator may confound study results or place subjects at undue risk.
• Biologics therapy: Received rituximab within 4 months of expected CAR T treatment: No plasma exchange or immunoglobulin treatment within 4 weeks prior to screening. MS patients: No high dose corticosteroid treatment in the 30 days prior to enrollment; see also section 9.1 for the list of restrictions.
• Participated in any clinical study within 3 months prior to enrollment, or participate in other clinical investigations during the study period.
• Previous or concurrent malignancy with the following exceptions: Adequately treated basal cell or squamous cell carcinoma, in situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening. A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening.
• Transplantation: History of vital organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/or bone marrow transplantation.
• Disease-specific criteria: MS/NMO patients: No disease relapse in the 30 days prior to enrollment
• Known HIV positive status.
• Active hepatitis B or C infection.
• Active CMV infection
• Pregnant or lactating women.
• Inability to understand or follow the research protocol subject requirements.
• Have any other clinically significant disease history or current disease that, in the judgment of the research physician, may pose a risk to the safety of the subjects, or interfere with the completion of the research procedure and the evaluation of safety and efficacy

Where it is running

• Hadassah MO — Jerusalem, Israel (enrolling)

Full record on ClinicalTrials.gov

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