Clinical trial NCT06513338: Complement C5 mAb in the Treatment of Anti-GBM Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autoimmune Diseases
Keywords: complement C5
anti0-GBM disease
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2024-07-22
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria

1. positive circulating anti-GBM antibody, with proteinuria or hematuria or any clinical signs of kidney injuries.
2. biopsy-proven anti-GBM disease with or without positive circulating anti-GBM antibodies 3.16\~65 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. ANCA-positive;
5. pregnant or lactating
6. Received investigational drug within 30 days or 4 half-lives (whichever is longer) prior to screening;
7. 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.;
8. 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;

Primary outcomes:
measure: kidney prognosis
timeFrame: 12 months after the last infusion of eculizumab
Secondary outcomes:
measure: side effects of eculizumab
timeFrame: 12 months after the last infusion of eculizumab
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
Study officials:
affiliation: PKUFH
name: Zhao Cui
role: PRINCIPAL_INVESTIGATOR
References: