IMAGINATION: A Global Phase 3 Trial of RO7434656, an Antisense Oligonucleotide Inhibitor of Complement Factor B, in IgA Nephropathy
Bibliographic record
Abstract
Background: RO7434656 (IONIS-FB-LRx, ISIS 696844), a ligand-conjugated antisense oligonucleotide targeting complement factor B mRNA, was engineered for enhanced delivery to the liver as the primary site of factor B production. In a Phase 2 trial (NCT04014335), RO7434656 inhibited alternative complement pathway activation and demonstrated a clinically meaningful reduction in UPCR resulting in a stable eGFR in patients with IgA nephropathy (IgAN; Fig 1).Fig 1.: Change in (A) UPCR and (B) Factor B in the Phase 2 Trial of RO7434656 (NCT04014335)Methods: IMAGINATION (NCT05797610), a Phase 3, randomized, double-blind, placebo-controlled trial will evaluate the efficacy and safety of RO7434656 in adults with biopsy-confirmed primary IgAN (Fig 2). 428 patients will be divided into 2 cohorts: a primary cohort with eGFR ≥30 mL/min/1.73m2 and an exploratory cohort with eGFR 20-29 mL/min/1.73m2. Patients on maximally tolerated doses of ACEi/ARB will be randomized 1:1 to receive RO7434656 or placebo subcutaneously (SC) on Days 1, 15 and 29 and every 4 weeks (Q4W) thereafter for 105 weeks, with the option to continue double-blind or open-label treatment. The primary endpoint is change from baseline in 24h UPCR at Week 37. Key secondary endpoints include eGFR slope from baseline at Week 105, time to the composite kidney failure endpoint and patient-reported outcomes. Blood, urine and optional kidney biopsies will be collected throughout the study to assess biomarkers.Fig 2.: Study Design of the Phase 3 IMAGINATION trial (NCT05797610)Results: Expected upon study completion. Conclusions: The unique antisense modality and long tissue half-life of RO7434656 enables Q4W SC administration to inhibit the alternative complement pathway. IMAGINATION aims to evaluate the efficacy and safety of RO7434656 in adults with IgAN using a broad range of assessments over 105 weeks. Funding: Commercial Support - Funded by F. Hoffmann-La Roche Ltd. Writing and editorial assistance was provided by Nicola Gillespie, DVM, CMPP, of Health Interactions, Inc. and funded by F. Hoffmann-La Roche Ltd.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 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".