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

NCT ID: NCT03945318

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-08
• Study Completion Date: 2026-04-13

Brief Summary

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).

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 will be conducted in three 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

Parts 1 and 2 have been completed. Part 3 enrollment is complete. Part 4 enrollment is open for eligible participants from Part 3.

The study will enroll up to 40 participants with IgAN.

Conditions

IgA Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part 1: BION-1301

Up to 5 cohorts with single ascending doses of BION-1301 administered by intravenous (IV) infusion.

Group Type: EXPERIMENTAL

BION-1301 Single Dose

Intervention Type: DRUG

A solution for IV infusion administered as a single dose.

Part 1: Placebo

Participants will receive a single dose of placebo administered by IV infusion.

Group Type: PLACEBO_COMPARATOR

Placebo Single Dose

Intervention Type: DRUG

A solution by IV infusion administered as a single dose.

Part 2: BION-1301

Up to 4 cohorts with multiple doses of BION-1301 administered by intravenous (IV) infusion.

Group Type: EXPERIMENTAL

BION-1301 Multiple Doses

Intervention Type: DRUG

A solution for IV infusion or SC injections (Part 3 only) administered as multiple doses.

Part 2: Placebo

Participants will receive placebo by IV infusion.

Group Type: PLACEBO_COMPARATOR

Placebo Multiple Doses

Intervention Type: DRUG

A solution by IV infusion administered as multiple doses.

Part 3: BION-1301

Two cohorts of participants will receive multiple doses of BION-1301 by IV infusion (Cohort 1) or SC injection (Cohort 2) at 600mg/biweekly.

Group Type: EXPERIMENTAL

BION-1301 Multiple Doses

Intervention Type: DRUG

A solution for IV infusion or SC injections (Part 3 only) administered as multiple doses.

Part 4 Retreatment: BION-1301

Eligible participants 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.

Group Type: EXPERIMENTAL

BION-1301 Single Dose

Intervention Type: DRUG

SC injection administration as a single dose using vials or pre-filled syringes (PFS) (Part 4 only).

Interventions

BION-1301 Single Dose

A solution for IV infusion administered as a single dose.

Intervention Type: DRUG

Placebo Single Dose

A solution by IV infusion administered as a single dose.

Intervention Type: DRUG

BION-1301 Multiple Doses

A solution for IV infusion or SC injections (Part 3 only) administered as multiple doses.

Intervention Type: DRUG

Placebo Multiple Doses

A solution by IV infusion administered as multiple doses.

Intervention Type: DRUG

BION-1301 Single Dose

SC injection administration as a single dose using vials or pre-filled syringes (PFS) (Part 4 only).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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

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 patient 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.

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

Exclusion Criteria

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 subject safety or interfere with the study, or would make the subject 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

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, Henoch-Schönlein purpura patients 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

1. Based on the Investigator's judgment, the patient would not benefit from resuming treatment with BION-1301 or there is a safety concern for the individual patient 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)

1. Based on the Investigator's judgment, the patient would not benefit from resuming treatment with BION-1301 or there is a safety concern for the individual patient 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Amicis Research Center

Northridge, California, United States

Colorado Kidney Care, P.C.

Denver, Colorado, United States

Nephrology Associates of Central Florida

Orlando, Florida, United States

Elixia Tampa, LLC

Tampa, Florida, United States

New York Nephrology

Clifton Park, New York, United States

Chris Sholer, P.C.

Oklahoma City, Oklahoma, United States

Liberty Research Center

Arlington, Texas, United States

Liberty Research Center

Dallas, Texas, United States

Prolato Clinical Research Center

Houston, Texas, United States

Soon Chun Hyang University Hospital Cheonan

Cheonan, Chungcheongnam-do, South Korea

Hallym University Sacred Heart Hospital

Anyang-si, Gyeonggi-do, South Korea

National Health Insurance Service Ilsan Hospital

Goyang-si, Gyeonggi-do, South Korea

Hanyang University Guri Hostpital

Guri-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Liverpool University Hospital NHS Foundation Trust

Liverpool, England, United Kingdom

PAREXEL Early Phase Clinical Unit

London, , United Kingdom

Countries

United States; South Korea; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40482854 (View on PubMed)

Other Identifiers

2018-003360-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CFUB523A12103

Identifier Type: -

Identifier Source: org_study_id

NCT04684745

Identifier Type: -

Identifier Source: nct_alias