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Kidney Week

Abstract: SA-PO885

IMAGINATION: A Global Phase 3 Trial of RO7434656, an Antisense Oligonucleotide Inhibitor of Complement Factor B, in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Barratt, Jonathan, University of Leicester Department of Cardiovascular Sciences, Leicester, United Kingdom
  • Floege, Jürgen, Division of Nephrology, University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany
  • Duggal, Vishal, Genentech Inc, South San Francisco, California, United States
  • Schmit, Nadine, F Hoffmann-La Roche AG, Basel, Switzerland
  • Cheng, Ji (Emmy), Hoffmann-La Roche Limited, Mississauga, Ontario, Canada
  • Lo, Jeannette, Genentech Inc, South San Francisco, California, United States
  • Rovin, Brad H., Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, Ohio, United States
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).

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.

Results

Expected upon study completion.

Conclusion

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.