A Phase IIa Study in Primary IgA Nephropathy Patients

A Multicenter, Single-arm, Open-label Study to Evaluate the Safety and Efficacy of XH-S003 in Patients With Primary IgA Nephropathy

This is a phase IIa, multicenter, single-arm, open-label study to evaluate the safety and efficacy of XH-S003 in patients with primary IgA nephropathy

Inclusion Criteria:

• Subjects must meet the following inclusion criteria:

  ● Male and female patients aged ≥18 years with a renal biopsy-confirmed diagnosis of primary IgA nephropathy:

  1. For patients with eGFR (CKD-EPI) ≥ 45 mL/min/1.73m2 at screening, a renal pathology biopsy within 10 years confirmed primary IgA nephropathy;

  2. For screening, eGFR (CKD-EPI) ≥30 and <45 mL/min/1.73m2 patients, within 2 years, diagnosed with primary IgA nephropathy through renal pathology biopsy;

  3. Renal pathology biopsy shows tubulointerstitial fibrosis < 50%;

  4. Renal pathology biopsy shows crescent formation in < 50% of glomeruli;

  5. If previous renal pathology biopsy results are unavailable, a biopsy needs to be performed during the screening period;

     • During screening and after completion of import eGFR (CKD-EPI) ≥ 30 mL/min/1.73 m2;
     • During screening and after completion of import, UPCR ≥ 0.75 g/g;
     • Before the first administration of medication, vaccination against Neisseria meningitidis and Streptococcus pneumoniae is required. If the patient has not been vaccinated before, or requires a booster, the vaccine should be administered at least 2 weeks prior to the first administration of medication. If the first administration of medication must begin earlier than 2 weeks after vaccination, prophylactic antibiotic therapy should be used until at least 2 weeks after vaccination;
     • Before the first administration, patients must have been on a stable treatment with the maximum tolerated dose of ACEi/ARB and SGLT2i for at least 90 days, and this treatment should remain unchanged during the study period. Additionally, if the patient is using diuretics or other antihypertensive treatments, the medication dosage should also be stable for at least 90 days before the first administration and remain unchanged during the study period;
     • After thoroughly understanding the nature, significance, potential benefits, possible inconveniences, and potential risks of the trial, and voluntarily participating in this clinical trial, the participant is able to communicate well with the researchers, comply with the requirements of the entire study, and has signed a written informed consent form.
     • Subjects of childbearing potential commit to having no plans for procreation, sperm or egg donation from screening to 1 month after the last dose (for females) or 3 months (for males), and voluntarily agree to use effective physical contraception methods (including their partners).

     Exclusion Criteria:

• Exclusion criteria include any of the following:

  • Secondary IgAN or those in whom secondary factors cannot be ruled out by investigator assessment;
  • Rapidly progressive IgA nephropathy (such as a decrease in eGFR (CKD-EPI) by ≥50% within 3 months, or less than 50% but with a risk of rapid decline in kidney function as assessed by the investigator);
  • Patients assessed by researchers to have other possible systemic diseases causing proteinuria (such as diabetic nephropathy, autoimmune diseases, antineutrophil cytoplasmic antibody-associated vasculitis, etc.); or those with severe urinary tract obstruction or dysuria; or other chronic kidney diseases (with or without kidney failure);
  • Known or suspected coalescence of immune deficiency diseases, hereditary complement deficiency as assessed by the researcher;
  • Any organ transplant recipient (excluding corneal transplant);
  • According to the investigator's assessment, blood pressure was inadequately controlled at screening (sitting blood pressure systolic >150 mmHg or blood pressure diastolic >90 mmHg);
  • Used immunosuppressants or other immunomodulatory drugs within 90 days prior to the first administration, or still within 5 half-lives of the drug, whichever is longer, specifically including but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, Mycophenolate Mofetil, Ciclosporin, tacrolimus, sirolimus, everolimus, systemic corticosteroids, etc.
  • Patients who have been treated with Endothelin receptor antagonists within the first 90 days before initial medication;
  • Individuals who have taken any decocted herbal products or used Jinshuibao, Bailing capsules, Huangkui capsules, Chinese patent medicines with immunosuppressive action (such as Tripterygium wilfordii preparations, Sinomenium acutum preparations, etc.), or other herbal products/Chinese patent medicines assessed by the researcher to have an impact on the trial assessment within 90 days prior to the first medication;
  • Patients who have previously or are currently receiving oral budesonide sustained-release tablets (Nefecon®, Nifukang®) for the treatment of IgAN;
  • During screening, individuals who are currently using hydroxychloroquine but have unstable treatment (except those who have been on stable treatment for at least 3 months prior to the first administration and can maintain this treatment unchanged throughout the study) or those planning to start using hydroxychloroquine during the study;
  • Patients with coalescence of systemic major diseases, including but not limited to: advanced stage heart disorder (such as NYHA Class IV), severe lung disease (such as severe pulmonary arterial hypertension (WHO Class IV), active hepatitis, or other systemic major diseases deemed unsuitable for participation in this study by the investigator;
  • During screening, individuals with significantly abnormal liver function: any parameter of ALT, AST, GGT, or alkaline phosphatase > 3 times the upper limit of normal (ULN); serum bilirubin total > 2 times ULN;14. Screening for human immunodeficiency virus (HIV) infection (HIV antibody positive), active syphilis infection, hepatitis B virus infection (hepatitis B surface antigen positive), active hepatitis C virus infection;
  • Active or latent tuberculosis during screening;
  • Individuals with a history of malignant neoplasm within the 5 years prior to screening (excluding carcinoma in situ and thyroid cancer that have been assessed by the researcher as having been radically resected);
  • History of Neisseria meningitidis infection;
  • Chronic active or recurrent infections within 1 year prior to screening, deemed unsuitable for participation in this study by the investigator, such as liver abscess, pyelonephritis, etc.;
  • Individuals with active systemic bacterial, viral (including COVID-19), or fungal infections requiring intravenous antibiotic treatment within 2 weeks prior to the first medication; those with an axillary body temperature >38°C within 7 days prior to the first medication;
  • Severe trauma or major surgery history within 3 months prior to screening, or plans to undergo major surgery during the trial;
  • History of blood donation or severe blood loss (blood volume ≥400mL) within 3 months prior to screening, or having received a transfusion within 3 months prior to screening;
  • Suspected or confirmed allergy to similar components of the investigational drug product or any components within the investigational drug product;
  • Pregnant or lactating women, or those with a positive pregnancy test;
  • History of drug abuse or substance use.
  • History of alcoholism within the 6 months prior to screening (average weekly consumption of ≥14 units of alcohol: 1 unit = 285 mL of beer; or 25 mL of spirits; or 125 mL of wine);
  • Participated in other clinical investigational drug trials (or still within 5 half-lives of the drug, whichever is longer) or medical device clinical trials within 30 days prior to screening, or plans to participate in other clinical trials during the study period, or if the investigator's assessment indicates the presence of residual effects;
  • Subjects assessed by the researcher to have diseases or medical conditions that affect drug absorption, distribution, metabolism, and excretion or may reduce compliance, such as a history of severe intestinal diseases, major gastrointestinal surgery, or the presence of dysphagia;
  • Researchers believe that any condition that may prevent subjects from completing this study or pose significant risks to the subjects, or patients deemed unsuitable to participate in this study by the researchers