CHT105 for the Treatment of Refractory Lupus Nephritis

Official title

A Clinical Study to Evaluate the Safety and Efficacy of CHT105, an Allogeneic CAR-T Cell Injection Targeting CD19 and CD70, in Patients With Refractory Lupus Nephritis

Overview

Systemic lupus erythematosus (SLE) is the most common systemic autoimmune disease in China. The kidneys are the organ most frequently affected in SLE and a major cause of mortality among SLE patients. Currently, cell-based therapy has emerged as an innovative treatment approach for SLE. CHT105 injection is an allogeneic chimeric antigen receptor T (CAR-T) cell product derived from healthy donors' T cells, which are transduced with a lentiviral vector encoding an anti-CD19/CD70 CAR. This engineered T-cell product effectively recognizes and eliminates immune cells expressing CD19 and/or CD70 antigens-including autoreactive T and B cells-and holds promise as a novel therapeutic option for patients with refractory lupus nephritis (LN). This study is a clinical trial evaluating the safety and preliminary efficacy of CHT105 injection-a CD19/CD70-targeting allogeneic CAR-T cell product-in adult patients with relapsed or refractory LN. Eligible participants will first undergo lymphodepleting preconditioning. Following confirmation of eligibility per standard infusion criteria, participants will receive a single intravenous infusion of CHT105 on Day 0 (D0). After CHT105 infusion, participants will undergo a 52-week short-term follow-up and up to a 15-year long-term follow-up.

Interventions

• Biological anti-CD19/70 CAR T cells (CHT105)
  All subjects will receive fludarabine/cyclophosphamide lymphodepletion followed by CHT105 infusion.

Primary outcome measures

• Safety of CHT105 Injection in Subjects with Refractory Lupus Nephritis [Time frame: From enrollment to the end of treatment at 52 weeks]

Secondary outcome measures (6)

• Complete Renal Response (CRR) [Time frame: at Week 24 after CHT105 infusion.]
• Partial Renal Response (PRR) [Time frame: At at Week 24 after CHT105 infusion.]
• Primary Efficacy Renal Response (PERR) [Time frame: At at Week 24 after CHT105 infusion.]
• Overall Renal Response (ORR) [Time frame: At at Week 24 after CHT105 infusion.]
• CRR, PRR, or PERR, and overall response rate [Time frame: At each follow-up visit between the first dose and Week 52.]
• the Systemic Lupus Erythematosus Responder Index-4 (SRI-4) criteria [Time frame: At each follow-up visit between the first dose and Week 52.]

Eligibility criteria

Inclusion criteria

• Age 18-65 years (inclusive), regardless of sex;
• Meets at least four of the 11 SLE classification criteria recommended by the American College of Rheumatology (ACR) in 1997; or fulfills the 2019 European League Against Rheumatism (EULAR)/ACR classification criteria for SLE;
• Diagnosed with active, biopsy-confirmed lupus nephritis (LN) class III or IV, with or without concurrent class V, according to the 2018 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification; renal biopsy must have been performed within one year prior to screening or during the screening period;
• Urine protein-to-creatinine ratio (UPCR) ≥ 1.0 g/g, or 24-hour urine protein ≥ 1.0 g, with or without active urinary sediment featuring red blood cell casts;
• Moderate-to-severe disease activity, as indicated by a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥ 6;
• At least one British Isles Lupus Assessment Group (BILAG-2004) A-grade (severe) organ domain score, or two B-grade (moderate) organ domain scores, or a combination thereof;
• Positive expression of CD19 and CD70 on peripheral blood B cells, as confirmed by flow cytometry;
• Refractory disease is defined as either failure to respond after ≥6 months of conventional therapy or recurrence of disease activity following prior remission. Conventional therapy includes glucocorticoids ± antimalarials, combined or sequentially administered with one or more of the following immunosuppressants: azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, leflunomide, thalidomide, tripterygium wilfordii, tacrolimus, cyclosporine A, sirolimus, voclosporin, JAK inhibitors (including those targeting JAK1/2/3 and TYK2), and biologics such as, but not limited to, anti-CD20 monoclonal antibodies, belimumab, and telitacicept;
• Female participants of childbearing potential and male participants whose partners are of childbearing potential must use medically approved contraceptive methods or abstain from sexual intercourse throughout the study treatment period and for at least six months thereafter; female participants of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) test within seven days prior to enrollment and must not be breastfeeding;
• Voluntarily participates in this clinical study, provides written informed consent, demonstrates good adherence, and agrees to comply with follow-up requirements.

Exclusion criteria

• Individuals with a history of severe drug allergy or allergic constitution;
• Presence of, or suspicion of, uncontrolled fungal, bacterial, viral, or other infections requiring hospitalization or intravenous therapy within one month prior to baseline;
• Any of the following cardiovascular or cerebrovascular events within six months prior to screening: unstable angina requiring hospitalization, myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention (diagnostic coronary angiography is permitted), moderate-to-severe congestive heart failure (NYHA Class III or IV), atrial or ventricular arrhythmias requiring hospitalization (e.g., atrial fibrillation, ventricular tachycardia), implantation of a pacemaker or defibrillator, cerebrovascular accident (e.g., stroke), or planned coronary artery bypass surgery or vascular reconstruction during the trial;
• Participants with congenital immunoglobulin deficiency;
• History of malignancy within the past five years (except for basal cell carcinoma, localized cutaneous squamous cell carcinoma, cervical carcinoma in situ, or thyroid carcinoma, all of which must have been definitively cured for at least one year);
• Participants with end-stage renal failure;
• Active tuberculosis risk at screening, regardless of whether adequate treatment has been completed-including signs or symptoms of active tuberculosis as judged by the investigator at screening (e.g., fever, cough, night sweats, weight loss); or evidence of active pulmonary tuberculosis on chest imaging (e.g., chest X-ray or chest CT scan) performed at screening or at any time within six months prior to screening;
• Participants who are positive for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb), with peripheral blood HBV DNA levels exceeding the upper limit of quantification; participants who are positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; participants who are positive for human immunodeficiency virus (HIV) antibody; or participants with a positive syphilis test;
• At screening, organ function must meet the following criteria:

a) Bone marrow function: i. Absolute neutrophil count < 0.8 × 10⁹/L (within two weeks prior to assessment, without administration of colony-stimulating factors, except in cases attributable to SLE); ii. Hemoglobin < 60 g/L (except in cases attributable to SLE); b) Hepatic function: ALT > 3 × ULN; AST > 3 × ULN; total bilirubin (TBIL) > 1.5 × ULN; c) Renal function: creatinine clearance (CrCl) < 30 mL/min (calculated using the Cockcroft-Gault formula, except in cases attributable to SLE); d) Coagulation function: international normalized ratio (INR) > 1.5 × ULN or prothrombin time (PT) > 1.5 × ULN;

• Presence of psychiatric disorders or severe cognitive impairment (excluding neuropsychiatric SLE);
• Participation in another clinical trial within one month prior to enrollment;
• Pregnant women or women planning pregnancy;
• Participants deemed ineligible for this study by the investigator for any other reason.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School — Nanjing

Identifiers

NCT: NCT07517536 · CHT105AIIT-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗