A Study of SGB-9768 in Patients with Complement-mediated Kidney Diseases

Official title

A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of SGB-9768 in Patients with Primary IgA Nephropathy, C3 Glomerulopathy, and Immune Complex-mediated Membranoproliferative Glomerulonephritis.

Overview

This study looks at how well and safely SGB-9768 works for patients with certain kidney diseases: primary IgA nephropathy, C3 glomerulopathy, and immune complex-related membranoproliferative glomerulonephritis. It's a phase 2 trial done at several locations where both patients and doctors know what treatment is being given.

Detailed description

This is a phase 2, multicenter, open-label study to evaluate of the efficacy and safety of SGB-9768 in patients with primary IgA nephropathy, C3 glomerulopathy, and immune complex-mediated membranoproliferative glomerulonephritis. The primary objective is to evaluate efficacy of SGB-9768 in reducing urine protein excretion and maintain kidney function in these patients. Secondly, safety, pharmacokinetics and pharmacodynamics will be charaterized.

Interventions

• Drug SGB-9768
  SGB-9768 for subcutaneous (SC) injection

Primary outcome measures

• change from baseline in urine protein-creatinine ratio (UPCR) [Time frame: 24 weeks]

Secondary outcome measures (10)

• change from baseline in UACR and 24h-urine protein [Time frame: 24 weeks]
• change from baseline in estimated glomerular filtration rate (eGFR) [Time frame: 36 weeks]
• Number of Participants with Adverse Events (AEs) and/or Serious Adverse Events (SAEs) [Time frame: from erollment through week 36]
• Pharmacokinetics-Cmax [Time frame: 24 hours]
• Pharmacokinetics-Tmax [Time frame: 24 hours]
• Pharmacokinetics-AUClast [Time frame: 24 hours]
• Pharmacokinetics-t1/2 [Time frame: 24 hours]
• Pharmacodynamics-C3 [Time frame: baseline through week 36]
• Pharmacodynamics-complement classical pathway activity by Wieslab® CP [Time frame: baseline through week 36]
• Pharmacodynamics-complement alternative pathway activity by Wieslab® AP [Time frame: baseline through week 36]

Eligibility criteria

Inclusion criteria

• Aged ≥18 years
• Weight ≥40 kg, with a body mass index (BMI) between 15 and 35 kg/m²
• Biopsy-confirmed diagnosis of primary IgA nephropathy, C3 glomerulopathy or IC-MPGN, accompanied by C3 deposition in the glomeruli.
• Urine protein-to-creatinine ratio (UPCR) ≥0.75 g/g
• Estimated glomerular filtration rate (eGFR) (calculated using the CKD-EPI formula) must be ≥30 mL/min/1.73 m².
• Must be on a stable maximum tolerated doses of ACE inhibitors (ACEI) or angiotensin receptor blockers (ARB) for at least 12 weeks
• Participants of childbearing potential must use highly effective contraception during the study and for at least 12 weeks following the end of the study or last dose of study drug

Exclusion criteria

• Kidney biopsy indicates more than 50% tubular atrophy or interstitial fibrosis.
• Kidney biopsy shows more than 50% formation of glomerular crescents, or clinical signs suggestive of rapidly progressive glomerulonephritis.
• IgA nephropathy, C3 glomerulopathy, or IC-MPGN secondary to other diseases
• Presence of other systemic diseases or kidney diseases that may cause proteinuria
• Received immunosuppressants or other immunomodulators within 90 days prior to the first administration of the investigational drug
• Received B-cell targeted biologics or other biologics within 180 days prior to the first administration of the investigational drug
• Used SGLT2 inhibitors or endothelin receptor antagonists, unless have been stably used for 12 weeks or more
• Significant comorbidities
• History of any malignant tumors of any organ system within the past 5 years
• History of severe trauma or major surgery within 12 weeks prior to screening, or plans to undergo surgery during the study.
• History of immunodeficiency diseases, congenital asplenia or splenectomy.
• History of recurrent invasive infections, active systemic bacterial, viral, or fungal infections
• Positive test results for HBV, HCV, HIV
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 2.5 times the upper limit of normal (ULN)

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

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 11 centers

• Peking University First Hospital — Beijing
• Peking University People's Hospital — Beijing
• The Third Xiangya Hospital of Central South University — Changsha
• Sichuan Provincial People's Hospital — Chengdu
• Guizhou Provincial People's Hospital — Guiyang
• The affiliated hospital of Guizhou medical university — Guiyang
• The first affiliated hospital, Zhejiang university school of medicine — Hangzhou
• Huashan hospital — Shanghai
• … and 3 more centers

Identifiers

NCT: NCT06786338 · SGB-9768-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗