A Phase I, open-label study of CTD402, a universal CD7-targeting CAR T-cell therapy, in patients with relapsed/refractory severe aplastic anemia Free

Severe Aplastic Anemia (SAA) is a bone marrow failure disorder mediated by abnormally activated T-lymphocytes that lead to hematopoietic stem cell destruction. The standard of care for patients ineligible for or without a matched sibling donor for hematopoietic stem cell transplantation (HSCT) is immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), cyclosporine (CsA), and a TPO-receptor agonist (TPO-RA). However, a substantial number of patients are refractory to or relapse after initial IST, leaving them with limited therapeutic options and a poor prognosis.

CD7 is a transmembrane glycoprotein highly expressed on T-cells and NK cells, which are central to the pathophysiology of SAA. CTD402 is a novel, allogeneic (“universal”) chimeric antigen receptor (CAR) T-cell therapy targeting CD7. Derived from healthy donors, CTD402, is a CD7 targeted “off-the-shelf” universal CAR-T product with T cell receptor and human leukocyte antigen class II knockout, and improved resistance to host immune rejection achieved by arming the cells with proprietary ANSWER^TM inhibitory ligands. Preclinical studies demonstrated potent in vitro cytotoxicity and in vivo anti-tumor activity. Furthermore, this universal CD7 CAR T platform has shown effective T-lymphocyte depletion in patients with hematological malignancies. This study aims to translate this mechanism to SAA, where targeted T-cell depletion may eliminate pathogenic immune cells and allow for the restoration of normal hematopoiesis. ClinicalTrials.gov registration: NCT06622694.Study Design and Methods This is a phase I, single-arm, open-label, “3+3” dose-escalation and dose-expansion study conducted at a single center in China. The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of RD13-02 in patients with relapsed/refractory SAA. Approximately 15 patients will be enrolled

The study will enroll adults aged 18 to 75 years with a confirmed diagnosis of SAA who are refractory to or have relapsed at least 6 months after a standard course of IST containing ATG/ALG and a TPO-RA. Key exclusion criteria include pancytopenia from other causes (e.g., hypoplastic MDS), prior allogeneic HSCT or CAR T-cell therapy, significant cardiovascular, hepatic or renal dysfunction, and active, uncontrolled infections.

Eligible patients will receive a standard lymphodepletion (sLD) regimen of fludarabine (25 mg/m²/day) and cyclophosphamide (500 mg/m²/day) for 3 days. This is followed by a single intravenous infusion of CTD402 cells. The dose-escalation phase will evaluate three dose levels (DL): DL1: 0.3×10⁸ CAR+ T cells；DL2: 0.5×10⁸ CAR+ T cells；DL3: 0.7×10⁸ CAR+ T cells.

The primary endpoint is to assess the safety and tolerability of RD13-02 and determine the maximum tolerated dose (MTD). Safety will be evaluated by the incidence of dose-limiting toxicities (DLTs), serious adverse events (SAEs), and other treatment-emergent adverse events (TEAEs). Key secondary endpoints include the overall hematologic response rate (ORR) at 3 and 6 months, duration of response, and the PK profile of RD13-02. Exploratory endpoints include the analysis of biomarkers related to immune reconstitution and disease activity.

The study is currently recruiting patients.