Complement C5 mAb in the Treatment of Anti-GBM Disease

A Single Center, Open-label, Single Arm Phase II Trial of the Efficacy and Safety of Complement C5 Monoclonal Antibody in the Treatment of Anti-glomerular Basement Membrane Disease

Anti-GBM disease is the most severe form of glomerulonephritis. Despite of the standard treatment including plasmapheresis and immunosuppressant, 70% of the patients still go into end-stage kidney disease. Complement has been shown to participate in the pathogenesis of anti-GBM disease. This study aims to the investigate the therapeutic effects and safety of C5 monoclonal antibody in the treatment of anti-GBM disease.

Study Overview

• Status: Completed
• Conditions: Autoimmune Diseases
• Intervention / Treatment: Drug: Eculizumab

Detailed Description

Anti-glomerular basement membrane (anti-GBM) disease is the most severe form of autoimmune glomerulonephritis, characterized by the production of autoantibodies targeting the components of basement membrane within the kidney and/or the lung.Patients with anti-GBM disease typically present rapidly progressive glomerulonephritis, and often accompanied by lung hemorrhage. The hallmark of the disease is the linear deposition of IgG along the GBM on kidney biopsy. Complement activation is a pivotal step for kidney injuries during the development of human anti-GBM disease. Our previous study showed that the The levels of plasma SC5b-9 and urinary C5a were positively correlated with the serum creatinine at presentation and the percentage of crescents in glomeruli. Eculizumab is a recombinant humanized monoclonal antibody that specifically binds to a C5 terminal complement and inhibits the cleavage of C5 to C5a and C5b through complement activation. There are a few case reports showing therapeutic effects in anti-GBM disease. This trial will aim to evaluate the efficacy and safety of Eculizumab plus standard treatment in anti-GBM disease.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100038
    • Peking University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Positive circulating anti-GBM antibody, with proteinuria or hematuria or any clinical signs of kidney injuries.
2. And or kidney biopsy showed typical IgG linear deposition along the GBM
3. At least 18 years old

Exclusion Criteria

1. Allergic to eculizumab, mouse protein or the investigational drug and any of its excipients;
2. Uncontrolled meningococcal infection,or those who have not received meningitis prophylactic antibiotic treatment or meningitis vaccination;
3. Diagnosis of anti-GBM disease for more than 12 weeks before signing the informed consent form;
4. Pregnant or lactating
5. Received investigational drug within 30 days or 4 half-lives (whichever is longer) prior to screening;
6. Other serious poorly controlled comorbid diseases that affect the compliance of the trial protocol or the interpretation of results within 3 months prior to screening, including cardiovascular and cerebrovascular diseases, lung disease, etc.;
7. Presence of any medical history or disease that, in the opinion of the investigator, may expose the patient's participation in the study to an unacceptable risk;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eculizumab; C5 monoclonal treatment plus standard treatment	Drug: Eculizumab; eculizumab 900mg iv. per week for 4 weeks, then 1200mg every two weeks for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
kidney prognosis	ESKD (dialysis dependent) or kidney translation	6 months after the first infusion of eculizumab

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in glomerular filtration rate (eGFR);	Change in level of estimated Glomerular Filtration Rate (eGFR) as measured by laboratory testing, reported in mL/min/1.73m².	from baseline to study completion, an average of 1 year
Changes in serum creatinine	Change in concentration of serum creatinine as measured by laboratory testing, reported in µmol/L	from baseline to study completion, an average of 1 year
Changes in blood urine nitrogen (BUN)	Change in concentration of Blood Urea Nitrogen (BUN) as measured by laboratory testing, reported in mmol/L	from baseline to study completion, an average of 1 year
side effects of eculizumab	The number of participants experiencing any adverse events determined by the investigator to be related to eculizumab treatment.	at 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
kidney function recovery	Kidney recovery was defined as independence from kidney replacement therapy (KRT, such as dialysis) lasting at least 12 weeks during follow-up	6 months after the first eculizumab infusion

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Zhao Cui, PKUFH

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): November 3, 2025
• Study Completion (Actual): November 3, 2025

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: complement C5; complement inhibition; crescentic glomerulonephritis; anti-GBM disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Glomerulonephritis; Nephritis; Autoimmune Diseases; Anti-Glomerular Basement Membrane Disease; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; eculizumab
• Other Study ID Numbers: C5mAb in anti-GBM disease

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No