Clinical trial NCT06607016: A Clinical Trial With KJ103 in Anti-GBM Disease
Official title: An Open-Label, Single-Arm Phase II Clinical Trial to Evaluate the Initial Efficacy, Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of KJ103 for the Treatment of Patients With Anti-Glomerular Basement Membrane Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Anti-Glomerular Basement Membrane Disease
Lead sponsor: Shanghai Bao Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-09-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An open-label, single-arm Phase II study to evaluate the preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenicity of KJ103 in patients with anti-GBM disease.

Detailed description: Anti-glomerular basement membrane (GBM) disease is a severe, rare autoimmune disorder with an internationally reported incidence of 0.5-1/1 million. It is defined as a vasculitis in which anti-GBM antibodies affect glomerular capillaries, pulmonary capillaries or both. Pulmonary involvement leads to pulmonary haemorrhage and renal involvement can lead to glomerulonephritis with necrosis and crescents.

Anti-GBM disease is a severe autoimmune disorder characterised by rapidly progressive glomerulonephritis and positive anti-GBM antibodies. Antibodies can be found in the circulation and deposited in the lungs and kidneys, mediating renal injury through complement activation and recruitment of inflammatory cells. If left untreated, the vast majority of patients will progress to end-stage renal disease (ESRD) or die from pulmonary haemorrhage. Early detection and measures to reduce anti-GBM antibody levels have the potential to alter prognosis and protect renal function. Unfortunately, many patients with anti-GBM disease are diagnosed late and renal function is not restored even with an aggressive treatment regimen of plasma exchange (PE) combined with immunosuppression. Current KDIGO (Kidney Disease Improving Global Prognosis Organisation) guidelines state that the clinical treatment of anti-GBM disease is a combination of glucocorticoids, cyclophosphamide and PE. Despite treatment, patients continue to produce anti-GBM antibodies in their bodies. Rebound anti-GBM antibodies are usually indicative of adverse renal outcomes and PE must be initiated to remove the rebound antibodies.PE is an effective means of removing circulating anti-GBM antibodies, but only removes about 1/3 of the percentage per treatment, so multiple treatments are required to achieve complete removal.

This is a single-arm Phase II study designed to evaluate the preliminary efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenicity of KJ103 in patients with anti-GBM disease. The trial is expected to enrol 9 to 12 subjects who will receive KJ103 treatment.

Eligibility criteria: Inclusion criteria:

1. Patients aged ≥18 years, both sexes.
2. Diagnosed with anti-GBM disease. Positive anti-GBM antibodies at screening, with or without ANCA antibody positivity.
3. With or without symptoms of haematuria and proteinuria.
4. Patients of childbearing potential who do not plan to have children during the study and for 6 months after the end of the study, or who are using effective contraception during sexual intercourse.

Exclusion criteria:

1. Anuria for more than 24 hours prior to the first dose.
2. Diagnosis of anti-GBM disease more than 14 days prior to first dose.
3. Moderate to severe pulmonary haemorrhage requiring mechanical ventilation during the screening period, including those occurring within two weeks prior to signing the informed consent form.
4. Severe renal disease not caused by anti-GBM disease, such as lupus nephritis, which, in the opinion of the investigator, makes them unsuitable for participation in this study.
5. Pregnant or breastfeeding at the time of screening.
6. Have a serious underlying medical condition other than anti-GBM disease, such as infection, autoimmune disease, respiratory disease, cardiovascular disease, central nervous system disease, etc., that the investigator deems unsuitable for participation in this trial.

Primary outcomes:
measure: Renal function
timeFrame: day 90, day 180
Secondary outcomes:
measure: Adverse events
timeFrame: day 180
measure: Proportion and number of subjects requiring PE
timeFrame: day 180
measure: Anti-GBM antibodies
timeFrame: day 180
measure: Immunogenicity
timeFrame: day 180
measure: eGFR and change from baseline.
timeFrame: Day28, Day60, Day90, Day120, Day150, Day180
measure: Pharmacokinetics of KJ103 (Cmax)
timeFrame: day 7
measure: Pharmacokinetics of KJ103 (AUC)
timeFrame: day 7
measure: Pharmacokinetics of KJ103 (t1/2)
timeFrame: day 7
measure: Pharmacokinetics of KJ103 (CL)
timeFrame: day 7
measure: Pharmacokinetics of KJ103 (Vz)
timeFrame: day 7
measure: Pharmacodynamic profile (Serum IgG levels)
timeFrame: day 180
measure: Pharmacodynamics-Anti neutrophil cytoplasmic antibodies (ANCA)
timeFrame: day 180
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
References: