IgA Nephropathy
Conditions
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 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.
Interventions
DRUGBION-1301 Single Dose
A single IV infusion infusion of BION-1301 at doses ranging from 10 to 1350 mg, administered once
A single IV infusion of placebo
DRUGBION-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.
Multiple IV infusions of placebo administered every 2 weeks for up to 3 doses
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Parts 1 and 2 were performed in a double-blind manner, for clinical research personnel interacting with study participants. An unblinded pharmacist prepared the doses of investigational study drugs.
Intervention model description
Part 1 (SAD-HV) is a randomized, placebo-controlled single ascending dose design in HVs. Part 2 (MAD-HV): is a randomized, placebo-controlled multiple ascending dose design in HVs. Part 3 (MD-IgAN) is an open-label multiple dose design in participants with IgAN. Part 4 (IgAN) is open-label retreatment for Part 3 participants.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Treatment Emergent Adverse Events (TEAEs) and treatment-emergent serious adverse events (SAEs) | Up to 276 weeks | 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). |
| Change from baseline in systolic and diastolic blood pressure | Baseline and up to 276 weeks. | Change from baseline in systolic and diastolic blood pressure |
| Change from baseline in estimated glomerular filtration rate (eGFR) | Baseline and up to 276 weeks | Change from baseline in estimated glomerular filtration rate (eGFR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Up to Day 85 | Maximum observed concentration |
| Tmax | Up to Day 85 | Time corresponding to occurrence of Cmax |
| T½ | Up to Day 85 | Apparent terminal elimination half life |
| AUC | Up to Day 85 | Area under the concentration-time curve (AUC) |
| Incidence of ADA and neutralizing antibodies (Nabs) | Up to 276 weeks | Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nabs) |
| Change from baseline in immunoglobulin levels | Baseline and up to 276 weeks | Change from baseline in immunoglobulin levels (IgA, IgG, IgM) |
| Change from baseline in UPCR | Up to 276 weeks | Change from baseline in urinary protein/creatinine ratio (UPCR) based on 24-hour urine collection |
| Change from baseline in urinary protein excretion | Up to 276 weeks | Change from baseline in urinary protein excretion based on 24-hour urine collection |
Countries
South Korea, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed