A Study of BION-1301 in Adults With IgA Nephropathy

• ClinicalTrials.gov Identifier: NCT05852938
• Recruitment Status: Recruiting
• First Posted: May 10, 2023
• Last Update Posted: April 19, 2024
• Sponsor: Chinook Therapeutics, Inc.
• Information provided by (Responsible Party): Chinook Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 2, 2023
• First Posted Date: May 10, 2023
• Last Update Posted Date: April 19, 2024
• Actual Study Start Date: July 27, 2023
• Estimated Primary Completion Date: January 19, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2023)

Change in proteinuria [ Time Frame: 40 weeks or approximately 9 months ]

The change in urine protein: creatinine ratio (UPCR) from baseline to Week 40.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 2, 2023)

Change in eGFR [ Time Frame: 104 weeks or approximately 2 years ]

The change in eGFR from baseline to Week 104.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of BION-1301 in Adults With IgA Nephropathy
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study of BION-1301 in Adults With IgA Nephropathy (The BEYOND Study)
• Brief Summary: Safety and Efficacy of BION-1301 in Adults with IgA Nephropathy

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Double-blind

Primary Purpose: Treatment

Condition

• IgA Nephropathy
• Immunoglobulin A Nephropathy

Intervention

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

Study Arms

• Experimental: BION-1301
  600mg subcutaneous administration every 2 weeks for 104 weeks
  Intervention: Drug: BION-1301
• Placebo Comparator: Placebo
  subcutaneous administration every 2 weeks for 104 weeks
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 12, 2023): 292
• Original Estimated Enrollment (submitted: May 2, 2023): 272
• Estimated Study Completion Date: May 8, 2028
• Estimated Primary Completion Date: January 19, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chinook Therapeutics, Inc.; (206) 485 - 7051; clinicaltrials@chinooktx.com

• Listed Location Countries: Argentina, Australia, Canada, Korea, Republic of, United States

Administrative Information

• NCT Number: NCT05852938
• Other Study ID Numbers: CHK02-02
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Chinook Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Chinook Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Chinook Therapeutics, Inc.
• Verification Date: April 2024