A Study of BION-1301 in Adults With IgA Nephropathy

IgA Nephropathy Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Placebo-controlled Study of BION-1301 in Adults With IgA Nephropathy (The BEYOND Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05852938
• Other study ID #: CHK02-02
• Status: Recruiting
• Phase: Phase 3
• Start date: July 27, 2023
• Est. completion date: May 8, 2028

Study information

• Verified date: May 2024
• Source: Chinook Therapeutics, Inc.
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

Approximately 272 patients with eGFR ≥ 30 mL/min/1.73m^2 and with biopsy-proven IgAN will be randomized to receive 600 mg Q2W BION-1301 or a matched placebo for 104 weeks. An additional exploratory cohort, not included in the primary analysis, will be comprised of approximately 20 subjects (10 subjects per arm) with biopsy-confirmed IgAN and eGFR of ≥ 20 to < 30 mL/min/1.73 m^2. The exploratory cohort will be randomized using the same schema as the primary cohort.

The primary objective of the study is to evaluate the effect of BION-1301 versus placebo on proteinuria in adults with IgA nephropathy.

Subjects will have assessments of safety and efficacy for 2.5 years (up to 134 weeks). To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 292
• Est. completion date: May 8, 2028
• Est. primary completion date: January 19, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• 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.

• eGFR = 30 mL/min/1.73m^2 at Screening based on the 2021 CKD-EPI equation.

• 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.

• 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.

• Body mass index (BMI) between 18 and 40 kg/m^2.

• Screening weight of 45 to 150 kg.

• 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.

• Provide written informed consent and be willing to comply with study visits and procedures.

Exclusion Criteria:

• Secondary forms of IgAN as determined by the Investigator, in the setting of systemic disorders, infections, autoimmune disorders or neoplasias.

• Diagnosis of IgA Vasculitis.

• Current or history of nephrotic syndrome.

• 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.

• Clinical suspicion of IgAN with rapidly progressive glomerulonephritis (RPGN) based on KDIGO guidelines

• Chronic Kidney Disease, either clinically suspected or based on biopsy, resulting from any condition or another glomerulopathy/podocytopathy other than IgAN.

• History of Type 1 Diabetes.

• 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:

• Prior exposure to any antibody directed against APRIL.

• 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.

• Received an investigational new drug within 28 days or 5 half-lives, whichever is longer, prior to Screening.

• Received systemic corticosteroid therapy including budesonide (Tarpeyo/Kinpeygo) for > 14 days within 12 weeks prior to Screening.

• Use of systemic immunosuppressant medications.

• 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.

• Current severe infection requiring antimicrobials or history of recurrent, severe, infections as determined by the Investigator.

• 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.

• 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.

• 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.

• Pregnancy or breastfeeding or intent to become pregnant or to donate sperm during the study period and until 24 weeks after last dose.

• 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.

• IgG levels < 6 g/L at Screening.

• Participation in another interventional trial with an investigational agent/device is prohibited during the course of this study.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Immunoglobulin A Nephropathy
• Kidney Diseases

Intervention

Drug:
• BION-1301
BION-1301 Pre-Filled Syringe (PFS) 600mg subcutaneous administration every 2 weeks for 104 weeks.
• Placebo
Placebo - PFS subcutaneous administration every 2 weeks for 104 weeks.

Locations

Country	Name	City	State
Argentina	Hospital Británico de Buenos Aires	Barracas	Ciudad Autónoma De BuenosAires
Argentina	Centro Médico Dra. Laura Maffei- Investigación Clinica Aplicada	Ciudad Autónoma de Buenos Aires
Argentina	Instituto Médico de la Fundación Estudios Clínicos	Rosario	Santa Fe
Argentina	Clínica de Nefrología Urología Y Enfermedades Cardiovasculares	Santa Fe
Australia	Box Hill Hospital-5 Arnold St	Box Hill	Victoria
Australia	Cairns Hospital	Cairns North	Queensland
Australia	Renal Research	Gosford	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Nepean Hospital	Penrith	New South Wales
Australia	Sunshine Hospital - Australia	St Albans	Victoria
Canada	Regional Kidney Wellness Centre	Brampton	Ontario
Canada	Stephen S. Chow Medicine Professional Corporation	East York	Ontario
Canada	London Health Sciences Centre	London	Ontario
Korea, Republic of	Seoul National University Hospital	Jongno-gu	Seoul Teugbyeolsi
United States	University of Colorado Hospital	Aurora	Colorado
United States	Northeast Clinical Research Center, LLC	Bethlehem	Pennsylvania
United States	Capital District Renal Physicians	Clifton Park	New York
United States	Columbia Nephrology Associates , P.A. - Columbia	Columbia	South Carolina
United States	Dallas Renal Group - 1411 N Beckley Ave	Dallas	Texas
United States	Dallas Renal Group - Waxachie - 2460 N. I-35	Dallas	Texas
United States	Denver Nephrology Research Division	Denver	Colorado
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	Nephrology Associates of Northern Virginia-8501 Arlington Blvd	Fairfax	Virginia
United States	Nephrology Associates PC - Flushing	Flushing	New York
United States	Nephrology Associates of Northern Illinois and Indiana - 7836 W Jefferson Blvd	Fort Wayne	Indiana
United States	Kidney Disease Medical Group Inc-1500 S Central Ave	Glendale	California
United States	Nephrology Associales of Northern Illinois and Indiana	Hinsdale	Illinois
United States	University of Texas MD Anderson Cancer Center-1155 Pressler	Houston	Texas
United States	IMD Clinical Trials	Huntington Park	California
United States	Nephrology Consultants, LLC	Huntsville	Alabama
United States	University Of Iowa Hospitals And Clinics	Iowa City	Iowa
United States	Knoxville Kidney Center, PLLC - Frenova F1	Knoxville	Tennessee
United States	East Texas Nephrology Associates	Lufkin	Texas
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Vida Medical Centers - Pembroke Pines	Pembroke Pines	Florida
United States	Valiance Clinical Research	S. Gate	California

Sponsors (1)

Lead Sponsor	Collaborator
Chinook Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in proteinuria	The change in urine protein: creatinine ratio (UPCR) from baseline to Week 40.	40 weeks or approximately 9 months
Secondary	Change in eGFR	The change in eGFR from baseline to Week 104.	104 weeks or approximately 2 years