IMAGINATION: A GLOBAL PHASE 3 TRIAL OF RO7434656, AN ANTISENSE OLIGONUCLEOTIDE INHIBITOR OF COMPLEMENT FACTOR B, IN IGA NEPHROPATHY

E-Poster

https://storage.unitedwebnetwork.com/files/1099/f6efe2b81ce1ebfb2e66ebaa511e8ead.pdf

Abstract Title

First Name *

Jonathan

Last Name *

Barratt

Co-author 1

Jürgen Flöge jfloege@ukaachen.de University Hospital, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Division of Nephrology Aachen

Co-author 2

Vishal Duggal duggal.vishal@gene.com Genentech, Inc. Clinical Science South San Francisco

Co-author 3

Nadine Schmit nadine.schmit@roche.com F. Hoffmann-La Roche Ltd PD Clinical Science Basel

Co-author 4

Ji Cheng emmy.cheng@roche.com Hoffmann-La Roche Ltd PD Data Sciences Mississauga

Co-author 5

Jeannette Lo lo.jeannette@gene.com Genentech, Inc. Translational Medicine South San Francisco

Co-author 6

Brad Rovin Brad.Rovin@osumc.edu The Ohio State University College of Medicine Department of Internal Medicine Columbus

Co-author 7

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

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 the urine protein-to-creatinine ratio (UPCR; Fig 1) and stabilization of the estimated glomerular filtration rate (eGFR) in patients with IgA nephropathy (IgAN).

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.

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.

This abstract was also submitted and accepted for presentation at ASN Kidney Week 2023. (Barratt J, Floege J, Duggal V, Schmit N, Cheng J, Lo J, Rovin BH: IMAGINATION: A Global Phase 3 Trial of RO7434656, an Antisense Oligonucleotide Inhibitor of Complement Factor B, in IgA Nephropathy [Abstract]. J Am Soc Nephrol 34, 2023: 974). Encore presentations of abstracts at meetings subsequent to Kidney Week are permitted by ASN.

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