Kidney Week

Abstract: TH-PO606

"RESULT" Umbrella Trial in Primary Focal Segmental Glomerulosclerosis/Minimal Change Disease

Session Information

• Membranous Nephropathy, FSGS, and Minimal Change Disease
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Lin, Julie, Sanofi, Cambridge, Massachusetts, United States

Julie Lin, MD, MPH, FASN

• Hu, An-Qi, Sanofi, Cambridge, Massachusetts, United States

An-Qi Hu, MD

• Liu, Shiguang, Sanofi, Cambridge, Massachusetts, United States

Shiguang Liu, MD, PhD

• Ocwieja, Karen, Sanofi, Cambridge, Massachusetts, United States

Karen Ocwieja, MD, PhD

• Uppara Kowthalam, Madhurima, Sanofi, Cambridge, Massachusetts, United States

Madhurima Uppara Kowthalam, MBBS

• Channi, Arjun Singh, Sanofi, Cambridge, Massachusetts, United States

Arjun Singh Channi, PharmD, MSc

• Hastings, Tara C., Sanofi, Cambridge, Massachusetts, United States

Tara C. Hastings, MA

• Luscan, Celine, Sanofi, Cambridge, Massachusetts, United States

Celine Luscan, MSc

• Turpault, Sandrine, Sanofi, Cambridge, Massachusetts, United States

Sandrine Turpault, PharmD, MSc

• Nigwekar, Sagar U., Massachusetts General Hospital, Boston, Massachusetts, United States

Sagar U. Nigwekar, MD

• Maski, Manish, Sanofi, Cambridge, Massachusetts, United States

Manish Maski, MD, MS

Background

Primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) continuum is a major cause of nephrotic syndrome among adult and pediatric patients. There is a lack of safe and effective therapies for FSGS/MCD, which is considered to be immune-mediated. We describe the protocol and operational feasibility for the Renal Efficacy Signaling UmbrelLa Trial (RESULT).

Methods

RESULT is an innovative global Phase 2a randomized, placebo-controlled umbrella trial that simultaneously evaluates the safety and efficacy of 3 novel therapies targeting immunological pathways implicated in primary FSGS/MCD: frexalimab (anti-CD40L monoclonal antibody), SAR442970 (anti-OX40L and anti-TNFα bispecific), and rilzabrutinib (BTK-inhibitor). Pts 16-75 years with biopsy-confirmed primary FSGS/MCD, eGFR ≥45 mL/min/1.73 m² and UPCR ≥3 g/g will enter a 12-wk double blind period followed by a 12-wk open-label extension (Fig). Primary endpoint is UPCR reduction from baseline to Wk 12 for each IMP vs pooled placebo. Operational feasibility has been conducted in 132 study sites across 23 countries.

Results

Majority (83%) of investigator responders expressed high interest in the trial, with top reasons being scientific importance (62%) and medical interest for patients (67%). Overall, 79% viewed burden of study procedures as appropriate, and 87% perceived remote study visits as safe. Interviews conducted with 11 affected adults, adolescents, and caregivers confirmed the high burden of disease, need for better therapies, and suitability of trial protocol.

Conclusion

This global RESULT Phase 2a trial utilizes an innovative efficacy signal-seeking master protocol to simultaneously evaluate 3 immunologically active therapies in FSGS/MCD and is the first umbrella trial in nephrology. Operational feasibility and stakeholder feedback demonstrate high scientific and medical interest, as well as appropriateness of trial design and assessments.

Funding

• Commercial Support – Sanofi