Study of SG301 for Renal AMR After Transplantation

This study is a prospective, single arm, open label Phase II clinical trial enrolling patients with antibody mediated rejection (AMR) after renal transplantation. It aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SG301 injection in this patient population, and to obtain preliminary efficacy signals through renal biopsy at Week 25 (assessed per Banff 2022 criteria) and changes in donor specific antibody (DSA) levels, among other measures.

Inclusion criteria

• Voluntarily sign the written informed consent form;
• Age ≥18 and ≤75 years;
• Expected survival ≥3 months;
• ≥180 days after renal transplantation, with stable graft function (from living or deceased donor);
• Biopsy-confirmed active or chronic active AMR (with or without peritubular capillary C4d deposition), per Banff 2022 classification;
• DSA: within 6 months prior to first dose, donor specific antibodies (DSA) specific to HLA class I and/or II antigens (pre existing and/or de novo) confirmed by local laboratory and meeting the local laboratory's positive definition;
• Estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m² at screening (CKD EPI formula);
• Recovery from adverse events due to prior treatment to ≤ Grade 1 (CTCAE v6.0), except for toxicities such as alopecia that are judged by the investigator to have no safety risk and not to violate other inclusion/exclusion criteria;
• Female participants of childbearing potential or male participants whose partners are of childbearing potential must remain abstinent or use reliable contraceptive measures during the study treatment period and for at least 6 months after the last dose of SG301. Male participants must refrain from sperm donation during the study and for at least 6 months after the last dose.

Exclusion criteria

• Concomitant T cell-mediated rejection (TCMR);
• New-onset or recurrent severe thrombotic microangiopathy; polyomavirus nephropathy; new-onset or recurrent glomerulonephritis;
• Prior treatment with other anti-CD38 monoclonal antibodies;
• Use of other monoclonal/polyclonal antibody immunosuppressive agents within 3 months prior to the first dose of study drug;
• Latent or active tuberculosis, or active viral (HBV, HCV, HIV, CMV), bacterial, or fungal infection requiring systemic therapy, or other active infections requiring systemic treatment;
• Active malignancy that makes the patient unsuitable for immunosuppressive therapy;
• Presence of serious medical or psychiatric illness that may interfere with the smooth conduct of the study;
• Prior multi-organ transplantation (including en bloc or dual kidney transplantation);
• Acute, rapid decline in renal function such that, in the investigator's judgement, the participant is likely to require renal replacement therapy within the subsequent 30 days;
• Receipt of any of the following treatments for AMR or TCMR within 3 months prior to the first dose of study drug (with the exception of glucocorticoids):

• Intravenous or subcutaneous immunoglobulin (IVIg/SCIg), plasma exchange, or immunoadsorption (antibody-depleting therapies);
• Complement system inhibitors (e.g., eculizumab);
• Proteasome inhibitors (e.g., bortezomib);
• Tocilizumab;
• Other investigational drugs within 3 months or 5 half-lives (whichever is longer) prior to start of study treatment;
• Female participants who are pregnant or breastfeeding;
• Other conditions that, in the investigator's judgement, would make the participant unsuitable for participation in the study.