Condition médicale (spécialité visée)
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Rhumatologie / Musculosquelettique / Inflammation
Rhumatologie
Profil des participants
Limites d'âge
Sexe(s) des participants
TOUS
Aptitude des participants
Majeurs aptes
Critères de sélection
Critères d'inclusion
Critères d'inclusion pour tous les sujets (Néphrite lupique ou SLE)
* Diagnostic de SLE selon les critères de classification 2019 de la Ligue Européenne contre le Rhumatisme/College Américain de Rhumatologie (EULAR/ACR)
* Les sujets doivent avoir eu une réponse inadéquate avec au moins deux lignes précédentes de traitement standard de soins (SoC).
Critères d'inclusion pour LN:
* Sujets adultes atteints de néphrite lupique de classe III ou IV (avec ou sans la présence de la classe V)
* Preuve de maladie active sur la biopsie rénale.
* Tous les sujets doivent recevoir un traitement antihypertenseur et antiprotéinurique adéquat concomitant avec le blocage du système rénine-angiotensine
Critères d'inclusion pour SLE:
* Indice d'activité de la maladie lupique systémique totale (SLEDAI-2K score) ≥ 8, et SLEDAI-2K clinique ≥ 4.
* Score d'activité du groupe d'évaluation du lupus des îles britanniques 2004 (BILAG-2004) de A dans ≥ 1 organe, ou un score d'activité BILAG-2004 de B dans ≥ 2 organes.
* Les sujets ont échoué à au moins deux thérapies conventionnelles
Critères d'exclusion:
* Antécédents connus de malignité passée ou actuelle
* Preuve clinique de maladies aiguës ou chroniques instables ou non contrôlées significatives non dues à la SLE
* Sujets avec des infections virales actives connues
* Lupus du SNC actif sévère
Inclusion Criteria for all subjects (Lupus Nephritis or SLE)
* Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria
* Subjects must have had an inadequate response with at least two prior lines of standard of care (SoC) treatment.
Inclusion Criteria for LN:
* Adult subjects with lupus nephritis Class III or IV (with or without the presence of Class V)
* Evidence of active disease on renal biopsy.
* All subjects are required to receive adequate concomitant antihypertensive and antiproteinuric therapy with blockade of the renin-angiotensin system
Inclusion Criteria for SLE:
* Total systemic lupus erythematosus disease activity index (SLEDAI-2K score) ≥ 8, and clinical SLEDAI-2K ≥ 4.
* British Isles Lupus Assessment Group 2004 (BILAG-2004) activity score of A in ≥ 1 organ, or a BILAG-2004 activity score of B in ≥ 2 organs.
* Subjects have failed at least two conventional therapies
Exclusion Criteria:
* Known past or current malignancy
* Clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE
* Subjects with known active viral infections
* Severe active CNS Lupus
Critères d'exclusion
1. Have severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 1.
2. Subjects who have received induction therapy with cyclophosphamide (CYC) within 3 months prior to Day 1.
3. Known hypersensitivity or contraindication to any drug products or any component of the drug products they plan to receive (e.g., CYC, fludarabine, rituximab, obinutuzumab, corticosteroids).
4. Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies or DMSO.
5. Received treatment with any B-cell targeted therapy within 4 months of the start of the planned lymphodepletion regimen (e.g., rituximab or obinutuzumab, other anti-CD20, anti-CD19 or anti- CD22 targeted agents)
6. Prior treatment with any autologous or allogeneic cell therapy approach using genetically modified immune cells (e.g., T, NK, macrophages or gamma-delta T cells modified with chimeric antigen receptors (CAR)).
7. Received any of the following within 6 months of the start of the planned lymphodepletion regimen:
• Immunoglobulin replacement therapies (IV or SC)
• Plasmapheresis.
8. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant, or are due to receive such transplantation.
9. Subjects who have been on dialysis within ≤1 year of Day 1
10. Known past or current malignancy except for:
• Cervical carcinoma of stage 1B or less
• Noninvasive basal cell or squamous cell skin carcinoma
• Noninvasive, superficial bladder cancer
• Prostate cancer with a current prostate specific antigen (PSA) level < 0.1 ng/m
• Any curable cancer with a complete response duration of > 2 years
i. with the exception of subjects with a history of B-cell malignancies (e.g., NHL, CLL/SLL, LPL/WM and Multiple Myeloma).
11. Known clinically significant cardiac disease, including:
• Onset of unstable angina pectoris within 6 months of signing the informed consent form
• Acute myocardial infarction within 6 months of signing the informed consent form
• Congestive heart failure (grade III or IV as classified by the New York Heart Association)
• Pericarditis present during screening or at baseline
• Heart rate-corrected QT interval (QTcF) prolongation > 470 msec at screening, unless secondary to stable conduction disorders (e.g., left bundle-branch block)
12. Unresolved toxicities from prior therapy, defined as having not resolved to Grade ≤ 1, or to the levels dictated in the eligibility criteria.
13. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE (e.g., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy, or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.
14. Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
15. Have any signs or symptoms of illness/infection or have received any vaccinations (live or inactivated) within 6 weeks of Day 1.
16. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or
dependence within ≤1 year prior to Day 1.
17. Human immunodeficiency virus (HIV) infection, based on laboratory testing performed during the screening period
18. Active hepatitis C virus (HCV) infection, based on laboratory testing performed during screening period. Subjects with a history of hepatitis B virus (HBV) infection are considered eligible only if their viral load is below the institutional limit of quantification (LOQ) and the subject is on stable viral suppressive therapy. HCV infected subjects are considered eligible if they have completed curative antiviral treatment and their HCV RNA viral load is below the institutional LOQ
19. Live vaccine administration planned or required during the treatment period of the trial.
20. Currently pregnant or lactating (breast feeding must not be started within 6 months of the last dose of AB-101).
21. Any other considerations that might interfere with the assessment of safety or efficacy, or that the investigator deems inappropriate for inclusion.
22. Any medical, psychological, familial, or sociological conditions that, in the opinion of the Investigator or Sponsor’s Medical Monitor, would impair the ability of the subject to receive study treatment or comply with study requirements, including understanding and granting informed consent.
23. Severe disease progression or health deterioration within 2 weeks of Day 1 that, in the opinion of the Investigator, could impair the ability of the subject to receive study treatment or comply with study requirements.
24. Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, voclosporin, etc., or chronic administration of >10 mg/day of prednisone) within 14 days of the start of the planned lymphodepletion regimen (exceptions to this exclusion criterion are topical and inhaled corticosteroids in standard doses, and physiologic steroid replacement for subjects with adrenal insufficiency). Prospective subjects being maintained on higher doses of corticosteroids may be enrolled if they can be tapered to <10 mg/day of prednisone (or equivalent) by 14 days before the start of the lymphodepletion regimen.
25. Known past or current clinically significant lung disease, including:
• Any pulmonary manifestations of SLE (i.e., pleurisy, pleural effusion, pulmonary hemorrhage/vasculitis, interstitial lung disease, and shrinking lung syndrome)
• History of, or current, chronic pulmonary disease (e.g., COPD, asthma, etc.) not meeting DLCO and FEV1 eligibility criteria
• Current use of tobacco products
26. Current or a medical history of hypogammaglobulinemia.