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

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.

Inclusion criteria

for Healthy Volunteers:

• Healthy male or female volunteers, 18 to 55 years old
• Females must be of non-childbearing potential
• Males must agree to follow the protocol-specified contraception guidance
• Body mass index (BMI) between 18 and 35 kg/m^2, with a weight of at least 50 kg
• 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
• Able to provide signed informed consent

Exclusion criteria

for Healthy Volunteers:

• 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
• 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
• 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
• 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:

• Male or female ≥18 years old at Screening
• 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)
• 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)
• BMI between 18 and 40 kg/m^2, inclusive, at Screening with a weight of at least 50 kg
• Diagnosis of IgAN verified by biopsy taken within the past 10 years
• Urine protein ≥ 0.5 g/24h; OR UPCR ≥ 0.5 g/g (or ≥ 50 mg/mmol)
• eGFR (per Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) or measured GFR ≥ 30 mL/min per 1.73 m^2
• 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:

• Known or suspected allergy or hypersensitivity to any component of BION-1301, or history of severe hypersensitivity reaction to any monoclonal antibody
• 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
• 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
• Secondary forms of IgAN as defined by the treating physician (eg, IgA vasculitis and those with associated alcoholic cirrhosis)
• 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

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

• 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.
• 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
• 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
• Received investigational products for the treatment of IgAN, other than BIO-1301
• 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

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

Exclusion criteria

for Optional Re-treatment

• 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.
• 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
• 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
• Received investigational products for the treatment of IgAN, other than BIO-1301
• Received newly approved immunosuppressive or immunomodulatory therapy for the treatment of IgAN including but not limited to other anti-APRIL therapies and iptacopan