Safety and Tolerability of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy (IgAN)

A Phase 1/2, Multicenter Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy

Multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BION-1301 in healthy volunteers and adults with IgA Nephropathy (IgAN).

Study Overview

• Status: Completed
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: BION-1301 Single Dose; Drug: BION-1301 Single Dose; Drug: Placebo Single Dose; Drug: BION-1301 Multiple Doses; Drug: Placebo Multiple Doses

Detailed Description

This is a Phase 1/2 study of BION-1301, a first-in-class humanized IgG4 anti-a proliferation-inducing ligand (APRIL) monoclonal antibody.

The study was conducted in four parts. Part 1: double-blind, randomized, placebo-controlled, single ascending dose (SAD) in healthy volunteers (HVs). Part 2: double-blind, randomized, placebo-controlled multiple ascending dose (MAD) in HVs. Part 3: Open-label, multiple dose (MD) in participants with IgAN. Part 4: Retreatment period

The study planned to enroll up to 40 participants with IgAN.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Korea
  • Chungcheongnam-do
    • Cheonan, Chungcheongnam-do, South Korea, 31151
      • Soon Chun Hyang University Hospital Cheonan
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, South Korea, 14068
      • Hallym University Sacred Heart Hospital
    • Goyang-si, Gyeonggi-do, South Korea, 10444
      • National Health Insurance Service Ilsan Hospital
    • Guri-si, Gyeonggi-do, South Korea, 11923
      • Hanyang University Guri Hostpital
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
• United Kingdom
  • London, United Kingdom, HA1 3UJ
    • PAREXEL Early Phase Clinical Unit
  • England
    • Liverpool, England, United Kingdom, L7 8XP
      • Liverpool University Hospital NHS Foundation Trust
• United States
  • California
    • Northridge, California, United States, 91324
      • Amicis Research Center
  • Colorado
    • Denver, Colorado, United States, 80230
      • Colorado Kidney Care, P.C.
  • Florida
    • Orlando, Florida, United States, 32806
      • Nephrology Associates of Central Florida
    • Tampa, Florida, United States, 33618
      • Elixia Tampa, LLC
  • New York
    • Clifton Park, New York, United States, 12065
      • New York Nephrology
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Chris Sholer, P.C.
  • Texas
    • Arlington, Texas, United States, 76012
      • Liberty Research Center
    • Dallas, Texas, United States, 75230
      • Liberty Research Center
    • Houston, Texas, United States, 77054
      • Prolato Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Healthy Volunteers:

1. Healthy male or female volunteers, 18 to 55 years old
2. Females must be of non-childbearing potential
3. Males must agree to follow the protocol-specified contraception guidance
4. Body mass index (BMI) between 18 and 35 kg/m^2, with a weight of at least 50 kg
5. Non-smoker, defined as an individual who has not smoked previously and/or who has discontinued smoking or the use of nicotine/nicotine-containing products at least 3 months before Screening
6. Able to provide signed informed consent

Exclusion Criteria for Healthy Volunteers:

1. Regular consumption of alcohol within 6 months prior to Screening, or use of soft drugs (such as marijuana) within 3 months prior to Screening, or hard drugs (such as cocaine and phencyclidine) within 1 year prior to Screening and/or positive blood or urine test results for drugs of abuse or alcohol at Screening or Admission
2. Donated blood in the 3 months prior to the first dose of study drug, plasma in the 7 days prior to the first dose of study drug, or platelets in the 6 weeks prior to the first dose of study drug
3. History or evidence of a clinically significant disorder, condition, or disease that could pose a risk to participant safety or interfere with the study, or would make the participant unsuitable for participation, eg, respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, or psychiatric disease
4. Female who is breastfeeding or who has a positive serum pregnancy test at Screening or a positive urine pregnancy test on Day -1

Inclusion Criteria for Adults with IgAN:

1. Male or female ≥18 years old at Screening
2. Women of child-bearing potential (WOCBP; per CTFG 2014) must agree to follow the protocol-specified contraception guidance throughout the study (from Screening through approximately 6 months after the final dose of study drug)
3. Males must agree to follow the protocol-specified contraception guidance throughout the study (from Screening through approximately 6 months after the final dose of study drug)
4. BMI between 18 and 40 kg/m^2, inclusive, at Screening with a weight of at least 50 kg
5. Diagnosis of IgAN verified by biopsy taken within the past 10 years
6. Urine protein ≥ 0.5 g/24h; OR UPCR ≥ 0.5 g/g (or ≥ 50 mg/mmol)
7. eGFR (per Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) or measured GFR ≥ 30 mL/min per 1.73 m^2
8. Stable on an optimized dose of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin-receptor blockers (ARBs) for at least 3 months prior to Screening or intolerant to ACE/ARB

Exclusion Criteria for Participant with IgAN:

1. Known or suspected allergy or hypersensitivity to any component of BION-1301, or history of severe hypersensitivity reaction to any monoclonal antibody
2. Donated blood in the 3 months prior to the first dose of study drug; plasma in the 7 days prior to the first dose of study drug; or platelets in the 6 weeks prior to the first dose of study drug
3. Participated in any other study in which receipt of an investigational new drug, or investigational device occurred within 28 days, or 5 half-lives (whichever is longer) of first dose of study drug in the present study
4. Secondary forms of IgAN as defined by the treating physician (eg, IgA vasculitis and those with associated alcoholic cirrhosis)
5. Received systemic corticosteroid therapy (> 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 3 months prior to the first dose of study drug

PART 4 Eligibility Criteria for Re-treatment Due to Evidence of Disease Progression

(Option 1) Inclusion Criteria for Re-treatment Due to Evidence of Disease Progression

1. Completed Part 3 of the study through Week 124 and entered the 52-week follow-up period.
2. UPCR ≥ 0.5 g/g AND ≥ 30% increase from EOT (Week 124). Both proteinuria criteria must be met by a 24-hour urine assessment during the 52-week follow-up period. In addition to the scheduled assessments, investigators may order periodic FMV assessments (for example monthly) to follow a participant more closely. Based on an off-schedule FMV result, or other laboratory or clinical evidence, investigators may order an off-schedule 24-urine collection to confirm disease progression.

Exclusion Criteria for Re-treatment Due to Evidence of Disease Progression

1. Based on the Investigator's judgment, the participant would not benefit from resuming treatment with BION-1301 or there is a safety concern for the individual participant which outweighs the expected benefit from resuming treatment.
2. Received systemic corticosteroid therapy, including budesonide, for >14 days within 3 months prior to the first dose of Part 4 for the treatment of IgAN
3. Received any other form of immunosuppressive therapy such as, but not limited to mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, rituximab, cyclophosphamide, etc) within 3 months prior to the first dose of Part 4 study drug
4. Received investigational products for the treatment of IgAN, other than BIO-1301
5. Received newly approved immunosuppressive or immunomodulatory therapy for the treatment of IgAN including but not limited to other anti-APRIL therapies and iptacopan

Eligibility Criteria for Optional Re-treatment (Option 2)

Inclusion Criteria for Optional Re-treatment

1. Completed Part 3 of the study through Week 124 and completed of the 52-week follow-up period.

Exclusion Criteria for Optional Re-treatment

1. Based on the Investigator's judgment, the participant would not benefit from resuming treatment with BION-1301 or there is a safety concern for the individual participant which outweighs the expected benefit from resuming treatment.
2. Received systemic corticosteroid therapy, including budesonide, for >14 days within 3 months prior to the first dose in Part 4 for the treatment of IgAN
3. Received any other form of immunosuppressive therapy (such as, but not limited to mycophenolate mofetil, azathioprine, cyclosporine, tacrolimus, rituximab, cyclophosphamide, etc) within 3 months prior to the first dose of Part 4 study drug
4. Received investigational products for the treatment of IgAN, other than BIO-1301
5. Received newly approved immunosuppressive or immunomodulatory therapy for the treatment of IgAN including but not limited to other anti-APRIL therapies and iptacopan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: BION-1301; Up to 5 cohorts with single ascending doses of BION-1301 administered by intravenous (IV) infusion in healthy volunteers.	Drug: BION-1301 Single Dose; A single IV infusion infusion of BION-1301 at doses ranging from 10 to 1350 mg, administered once; Other Names: Zigakibart; FUB523; Drug: BION-1301 Single Dose; 600 mg SC injection every 2 weeks (Q2W) for retreatment, administered via vials or pre-filled syringes (PFS); Other Names: Zigakibart; FUB523
Placebo Comparator: Part 1: Placebo; Healthy Volunteers receive a single dose of placebo administered by IV infusion.	Drug: Placebo Single Dose; A single IV infusion of placebo
Experimental: Part 2: BION-1301; Up to 4 cohorts with multiple doses of BION-1301 administered by intravenous (IV) infusion in healthy volunteers.	Drug: BION-1301 Multiple Doses; Part 2: Multiple IV infusions of BION 1301 administered every 2 weeks (Q2W) at doses of 50 mg, 150 mg or 450 mg for up to 3 doses. Part 3: Repeated dosing of BION 1301: 450 mg IV Q2W for ≥24 weeks followed by 600 mg SC Q2W, or 600 mg SC Q2W throughout.; Other Names: Zigakibart; FUB523
Placebo Comparator: Part 2: Placebo; Healthy Volunteers receive placebo by IV infusion.	Drug: Placebo Multiple Doses; Multiple IV infusions of placebo administered every 2 weeks for up to 3 doses
Experimental: Part 3: BION-1301; Two cohorts of participants with IgAN receive multiple doses of BION-1301 by IV infusion (Cohort 1) or SC injection (Cohort 2) at 600mg/biweekly.	Drug: BION-1301 Multiple Doses; Part 2: Multiple IV infusions of BION 1301 administered every 2 weeks (Q2W) at doses of 50 mg, 150 mg or 450 mg for up to 3 doses. Part 3: Repeated dosing of BION 1301: 450 mg IV Q2W for ≥24 weeks followed by 600 mg SC Q2W, or 600 mg SC Q2W throughout.; Other Names: Zigakibart; FUB523
Experimental: Part 4 Retreatment: BION-1301; Eligible participants with IgAN from Part 3 may enroll in Part 4 due to disease progression or by choice for optional retreatment and receive SC injection at 600mg/biweekly.	Drug: BION-1301 Single Dose; A single IV infusion infusion of BION-1301 at doses ranging from 10 to 1350 mg, administered once; Other Names: Zigakibart; FUB523; Drug: BION-1301 Single Dose; 600 mg SC injection every 2 weeks (Q2W) for retreatment, administered via vials or pre-filled syringes (PFS); Other Names: Zigakibart; FUB523

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment Emergent Adverse Events (TEAEs) and treatment-emergent serious adverse events (SAEs)	TEAEs and SAEs are assessed throughout each participant's study participation according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).	Up to 276 weeks
Change from baseline in systolic and diastolic blood pressure	Change from baseline in systolic and diastolic blood pressure	Baseline and up to 276 weeks.
Change from baseline in estimated glomerular filtration rate (eGFR)	Change from baseline in estimated glomerular filtration rate (eGFR)	Baseline and up to 276 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed concentration	Up to Day 85
Tmax	Time corresponding to occurrence of Cmax	Up to Day 85
T½	Apparent terminal elimination half life	Up to Day 85
AUC	Area under the concentration-time curve (AUC)	Up to Day 85
Incidence of ADA and neutralizing antibodies (Nabs)	Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nabs)	Up to 276 weeks
Change from baseline in immunoglobulin levels	Change from baseline in immunoglobulin levels (IgA, IgG, IgM)	Baseline and up to 276 weeks
Change from baseline in UPCR	Change from baseline in urinary protein/creatinine ratio (UPCR) based on 24-hour urine collection	Up to 276 weeks
Change from baseline in urinary protein excretion	Change from baseline in urinary protein excretion based on 24-hour urine collection	Up to 276 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Kooienga L, Lo J, Lee EY, Kim SG, Thomas H, Workeneh B, Agha I, Song Y, Smith W, van Eenennaam H, Van Elsas A, Dulos J, Barratt J. Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy. Kidney Int. 2025 Sep;108(3):445-454. doi: 10.1016/j.kint.2025.05.006. Epub 2025 Jun 5.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2019
• Primary Completion (Actual): June 10, 2026
• Study Completion (Actual): June 10, 2026

Study Registration Dates

• First Submitted: April 21, 2019
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): June 16, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: May 1, 2026

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; Glomerulonephritis; Nephritis; Glomerulonephritis, IGA
• Other Study ID Numbers: CFUB523A12103; ADU-CL-19 (Other Identifier: Chinook Code); 2018-003360-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

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