Safety and Efficacy of BION-1301 in Adults with IgA Nephropathy

JRCT ID: jRCT2061240045

Registered date:06/08/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: IgA Nephropathy
• Date of first enrollment: 18/07/2024
• Target sample size: 23
• Countries of recruitment: US,Japan,South Korea,Japan,Malaysia,Japan,Canada,Japan,Australia,Japan,Mexico,Japan,India,Japan,Brazil,Japan,UK,Japan,Spain,Japan,Argentina,Japan,Greece,Japan,France,Japan,Italy,Japan,Germany,Japan,Belgium,Japan,Czech Republic,Japan,Israel,Japan,Turkey,Japan,Croatia,Japan,Taiwan,Japan,China,Japan
• Study type: Interventional
• Intervention(s): Subjects will be randomized 1:1 to receive BION-1301 600 mg Q2W or a matched placebo for 104 weeks.

Outcome(s)

• Primary Outcome: Change in proteinuria (urine protein:creatinine ratio [UPCR]) based on 24-hour urine collection from Baseline to Week 40
• Secondary Outcome: Change from Baseline to Week 104 in eGFR using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI 2021) creatinine equation.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Male and female subjects aged >= 18 years at the time of signing the informed consent form (ICF) prior to initiation of any study specific activities/procedures.
2. Biopsy-proven IgAN diagnosed within the past 10 years prior to Screening, that, in the opinion of the Investigator, is not due to secondary causes. A pseudonymized copy of the report must be available for review by the Sponsor or designee prior to randomization. If biopsy report within 10 years is not available, re-biopsy may be permitted upon discussion with the Medical Monitor.
3. eGFR >= 30 mL/min/1.73m2 at Screening based on the 2021 CKD-EPI equation.
4. Total urine protein >= 1.0 g/day and UPCR >= 0.7 g/g (700 mg/g), as measured from an adequate 24-hour urine collection at Screening by a central laboratory.
5. Stable on a maximally tolerated dose of ACEi/ARB for at least 12 weeks prior to Screening unless intolerant to ACEi/ARB. May also be on a stable and well tolerated dose of SGLT2i and/or ERAs/MRAs for at least 12 weeks prior to Screening for the treatment of IgAN. Subjects are expected to stay on the ACEi/ARB, SGLT2i, and/or the ERAs/MRAs for the duration of the study.
6. Body mass index (BMI) between 18 and 40 kg/m2.
7. Screening weight of 45 to 150 kg.
8. Men and women of childbearing potential (WOCBP; per Clinical Trials Facilitation and Coordination Group [CTFG] 2020) must agree to follow protocol-specified contraception guidance from Screening through approximately 5 half-lives (24 weeks) after the final dose of study drug. Use of hormonal contraceptive agents must have been initiated > 1 month prior to first dose of study drug.
9. Provide written informed consent and be willing to comply with study visits and procedures.

Exclude criteria

1. Secondary forms of IgAN as determined by the Investigator, in the setting of systemic disorders, infections, autoimmune disorders or neoplasias.
2. Diagnosis of IgA Vasculitis.
3. Current or history of nephrotic syndrome.
4. Average blood pressure > 150/90 mm Hg (systolic/diastolic) from 3 readings obtained at the initial Screening visit. If blood pressure is too high, the 3 readings may be repeated once within the Screening period if clinically appropriate as per the Investigator.
5. Clinical suspicion of IgAN with rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines.
6. Chronic Kidney Disease, either clinically suspected or based on biopsy, resulting from any condition or another glomerulopathy/podocytopathy other than IgAN.
7. History of Type 1 Diabetes.
8. Subjects with Type 2 diabetes are excluded if any of the following are present:
- Screening HbA1c (glycated hemoglobin) of > 8%.
- Evidence of diabetic changes on kidney biopsy, performed for any reason.
- History of diabetic microvascular disease (retinopathy, neuropathy, nephropathy) and/or macrovascular disease (atherosclerotic heart disease, peripheral vascular disease, cerebrovascular disease).
- Unstable anti-diabetic regimen.
9. Prior exposure to any antibody directed against APRIL.
10. History of a previous severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis, including a history of allergy or hypersensitivity to any component of BION-1301, or history of severe hypersensitivity reaction to any monoclonal antibody.
11. Received an investigational new drug within 28 days or 5 half-lives, whichever is longer, prior to Screening.
12. Received systemic corticosteroid therapy including budesonide (Tarpeyo/Kinpeygo) for > 14 days within 12 weeks prior to Screening.
13. Use of systemic immunosuppressant medications.
14. Any confirmed or suspected immunosuppressive or immune-deficient state, including but not limited to common variable immunodeficiency (CVID), HIV infection or asplenia, history of bone marrow or organ transplantation with exception of corneal transplants.
15. Current severe infection requiring antimicrobials or history of recurrent, severe, infections as determined by the Investigator.
16. Positive serology test for hepatitis A virus IgM antibodies (anti-HAV IgM), hepatitis B surface antigen (HBsAg), detectable hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) antibodies (subjects who completed treatment and are persistently antibody be allowed), or antibodies to HIV-1 and/or HIV-2 at Screening.
17. Received a live vaccination within 12 weeks prior to Screening or plan to have a live vaccination within 6 months after the last dose of study drug.
18. History of malignancy unless cancer free for at least 5 years or non-melanoma skin cancer that was completely resected. A subject with curatively treated cervical carcinoma in situ is eligible for the study. Subjects with low-risk prostate cancer (i.e., Gleason score < 7 and prostate specific antigen < 10 ng/mL) are allowed.
19. Pregnancy or breastfeeding or intent to become pregnant or to donate sperm during the study period and until 24 weeks after last dose.
20. History or evidence of any other clinically significant disorder, condition, disease, or laboratory finding that, in the Investigator's assessment, would place the subject at unacceptable risk, limit compliance with study requirements, or confound interpretation of study results.
21. IgG levels < 6 g/L at Screening.
22. Participation in another interventional trial with an investigational agent/device is prohibited during the course of this study.

Related Information

• Primary Sponsor: Kawasaki Taichi
• Secondary ID(s): NCT05852938