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

NCT07085676 | Recruiting Phase 1 DMC

• 1 other identifier: HBI0101 ARD 001
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Sclerosis (SSc); Rheumatoid Arthritis (RA); Idiopathic Inflammatory Myopathy (IIM); 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

Keywords

B-cell mediated autoimmune rheumatic diseases; Systemic Lupus Erythematosus (SLE); Systemic sclerosis (SSC); Idiopathic inflammatory myopathy (IIM); Rheumatoid arthritis (RA); B-cell maturation antigen (BCMA); Autologous CAR-T; Multiple sclerosis (MS) Primary and Secondary progressive; Neuromyelitis Optica Spectrum Disorder (NMOSD); Myasthenia Gravis (MG); refractory antiphospholipid antibody syndrome

Outcome Measures

Primary Outcomes (2)

• Part A: Establishment of the initial safety profile of HBI0101 CAR T

  Incidence of adverse events (AEs) and abnormal laboratory test results used to determine the dose-limiting toxicities (DLTs).

  21 days after infusion

• Part B: Confirmation of safety with selected dose

  Incidence, severity and type of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) related to HBI0101 CART at the dose selected in Part A

  4 years after infusion

Secondary Outcomes (29)

• Overall survival

  3 months for up to 24 months, every 6 months for up to 48 months

• Four-year relapse/progression free survival: All Cohorts

  4 years following infusion

• Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort

  4 years following infusion

• Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort

  4 years following infusion

• Disease-specific response/progression endpoints: Systemic Lupus Erythematosus (SLE) cohort

  4 years following infusion

Study Arms (1)

BCMA CART

EXPERIMENTAL

Each subject subjects will receive a single dose of 450 x 10\^6 or 800 x 10\^6 BCMA CART cells

Biological: HBI0101 CART

Interventions

HBI0101 CART BIOLOGICAL

HBI0101 CART is defined as autologous T cells transduced ex-vivo with anti-BCMA CAR retroviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA. The HBI0101 CART may be provided fresh or cryopreserved.

BCMA CART

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.
• 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.

Sponsors & Collaborators

• Polina Stepensky: lead

Study Sites (1)

Hadassah MO

Jerusalem, 9574869, Israel

RECRUITING

Related Publications (2)

• Kfir-Erenfeld S, Asherie N, Grisariu S, Avni B, Zimran E, Assayag M, Sharon TD, Pick M, Lebel E, Shaulov A, Cohen YC, Avivi I, Cohen CJ, Stepensky P, Gatt ME. Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis. Clin Cancer Res. 2022 Dec 1;28(23):5156-5166. doi: 10.1158/1078-0432.CCR-22-0637.

  PMID: 36107221 BACKGROUND

• Asherie N, Kfir-Erenfeld S, Avni B, Assayag M, Dubnikov T, Zalcman N, Lebel E, Zimran E, Shaulov A, Pick M, Cohen Y, Avivi I, Cohen C, Gatt ME, Grisariu S, Stepensky P. Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Haematologica. 2023 Jul 1;108(7):1827-1839. doi: 10.3324/haematol.2022.281628.

  PMID: 36200421 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Myositis; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Multiple Sclerosis, Chronic Progressive; Neuromyelitis Optica; Myasthenia Gravis; Antiphospholipid Syndrome; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Neurodegenerative Diseases; Neuromuscular Junction Diseases

Central Study Contacts

Polina Stepensky, MD

CONTACT

972-2-6778353; Fainak@hadassah.org.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Polina Stepensky, Director Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Organization

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: July 25, 2025
• Study Start: September 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

IL (1)