MO207: A Phase 1/2, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BION-1301 in Healthy Volunteers and Adults with IGA Nephropathy
Bibliographic record
Abstract
Abstract BACKGROUND AND AIMS Immunoglobulin A nephropathy (IgAN) is the leading cause of primary glomerulonephritis worldwide with limited treatment options, especially for high-risk patients [1]. BION-1301 is a novel humanized monoclonal antibody that blocks a proliferation-inducing ligand (APRIL), a soluble factor that has been shown to be elevated in patients with IgAN and is correlated with poorer outcomes, including increased proteinuria and decreased eGFR [2, 3]. APRIL promotes IgA class switching, the survival of IgA-secreting plasma cells and the excess production of a galactose-deficient variant form of IgA1 (Gd-IgA1), which is an initiating step in the multi-hit pathogenesis of IgAN. This leads to the generation of anti-Gd-IgA1 autoantibodies and the formation of nephritogenic immune complexes that deposit in the kidney, resulting in inflammation and damage [2–4]. Blocking APRIL with BION-1301 is a novel approach to address the underlying pathogenesis of IgAN by reducing circulating levels of Gd-IgA1 and preventing the formation of pathogenic immune complexes. The primary objective of this Phase 1/2 study is to assess the safety and tolerability of BION-1301 in healthy volunteers (HV) and patients with IgAN, and secondarily to assess the PK, PD, immunogenicity and preliminary clinical activity. METHOD The Phase 1/2 study (NCT03945318) is comprised of three parts. Parts 1 and 2 were blinded, placebo-controlled single and multiple ascending dose designs in HV and have been completed. Part 3 is a multicenter (USA, UK, South Korea), multicohort, open-label study in up to 40 patients with IgAN. Patients in Cohort 1 receive 450 mg of BION-1301 administered IV every 2 weeks for up to 1 year. After completing at least 24 weeks of IV dosing, patients in Cohort 1 transitioned from receiving 450 mg of BION-1301 IV to receiving 600 mg of BION-1301 SC every 2 weeks. Patients in Cohort 2 receive 600 mg of BION-1301 SC every 2 weeks for up to 1 year. Additional cohorts may be added to explore other doses and dosing schedules. Key eligibility criteria for Part 3 include: (1) biopsy-verified diagnosis of IgAN within 10 years, (2) baseline urine protein excretion ≥ 0.5 g/24 h or UPCR ≥ 0.5 g/g and (3) stable/optimized dose of ACE-I/ARB (or intolerant). RESULTS Final HV data from Parts 1 and 2 have been presented at earlier conferences [5]. Part 3 is on-going and updated interim data from patients with IgAN in Cohort 1 who received BION-1301 IV as well as patients who transitioned to SC dosing are planned to be presented at the 59th ERA Congress. CONCLUSION The current design of the Phase 1/2 study incorporating SC dosing provides for an improved patient experience and will enable the generation of extended safety, PK, PD, immunogenicity and preliminary efficacy data for the potential use of BION-1301 in patients with IgAN.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".