A Clinical Trial With KJ103 in Anti-GBM Disease

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Anti-Glomerular Basement Membrane Disease
• Intervention / Treatment: Drug: Glucocorticoids; Drug: KJ103 for Injection; Drug: Cyclophosphamide; Procedure: Plasma exchange (PE)

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking University First Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Experimental Group; KJ103 +SOC(SoC consists of a standardized combination of PE, Cyclophosphamide, and glucocorticoids)

Drug: Glucocorticoids; Glucocorticoids inhibit the inflammation process.; Drug: KJ103 for Injection; Subjects will administered KJ103 intravenously on D1 and adjunctively on D8; Drug: Cyclophosphamide; Hence treatment prevents formation of new anti-GBM antibodies.; Procedure: Plasma exchange (PE); PLEX removes the patient's pathogenic anti-GBM antibodies, by replacement of deficient plasma with a replacement fluid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal function	Proportion of subjects with renal function after KJ103 administration.	day 90, day 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Assessing the incidence and severity of adverse events (AEs) and serious adverse events (SAEs) via the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	day 180
Proportion and number of subjects requiring PE	Proportion and number of subjects requiring PE after KJ103 administration.	day 180
Anti-GBM antibodies	Number of days positive for anti-GBM antibodies after KJ103 administration.	day 180
Immunogenicity	Immunogenicity of KJ103 (Anti-KJ103 antibody) in patients with anti-GBM disease.	day 180
eGFR and change from baseline.	Estimated glomerular filtration rate (eGFR). Glomerular filtration rate is an estimate of the amount of ultrafiltrate produced by each side of the kidney per unit of time and is an indicator of kidney function.	Day28, Day60, Day90, Day120, Day150, Day180
Pharmacokinetics of KJ103 (Cmax)	Maximum observed serum concentration of KJ103 following dosing (Cmax)	day 7
Pharmacokinetics of KJ103 (AUC)	Area under the serum concentration versustime curve (AUC)	day 7
Pharmacokinetics of KJ103 (t1/2)	Half-life of KJ103	day 7
Pharmacokinetics of KJ103 (CL)	Clearance(CL) is a measure of the ability of the body to clear KJ103	day 7
Pharmacokinetics of KJ103 (Vz)	Vz = Volume of distribution during the elimination phase	day 7
Pharmacodynamic profile (Serum IgG levels)	Serum IgG levels after KJ103 dosing	day 180
Pharmacodynamics-Anti neutrophil cytoplasmic antibodies (ANCA)	Serum Anti neutrophil cytoplasmic antibodies (ANCA) levels after KJ103 dosing	day 180

Collaborators and Investigators

• Sponsor: Shanghai Bao Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: September 17, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Glomerulonephritis; Nephritis; Anti-Glomerular Basement Membrane Disease; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Glucocorticoids
• Other Study ID Numbers: SHBJ-KJ103-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No