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Abstract: TH-PO498

A Phase 2a Study to Evaluate the Safety and Efficacy of Tegoprubart (AT-1501) in Patients With IgA Nephropathy (IgAN)

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
  • Liew, Adrian, Mount Elizabeth Medical Centre, Singapore, Singapore
  • Rizk, Dana, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Willcocks, Lisa, Addenbrooke's Hospital, Cambridge, Cambridgeshire, United Kingdom
  • Lafayette, Richard A., Stanford University School of Medicine, Stanford, California, United States
  • Wong, Muh Geot, The University of Sydney, Sydney, New South Wales, Australia
  • Tesar, Vladimir, Univerzita Karlova, Praha, Czechia
  • Bornstein, Jeffrey D., Eledon Pharmaceuticals, Irvine, California, United States
  • Reich, Heather N., University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
  • Tang, Sydney C.W., The University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, Hong Kong
Background

IgAN is the most common autoimmune nephropathy, with a young age of onset and a slow progressive course. ~40% of affected patients progress to kidney failure within 20 years of diagnosis. Therapeutic options that delay progression are limited, and more options are needed. Tegoprubart is a next generation monoclonal antibody directed against CD40 ligand (CD40L; CD154), a target important in both cell and antibody mediated immunity. Inhibiting CD40L is expected to disrupt the pathophysiology of IgAN both upstream, by blocking antibody and immune complex formation, and downstream, by interfering with the cell based inflammatory response in the glomeruli. A Phase 2a dose-finding, open-label study, AT-1501-N205, to evaluate the safety and efficacy of tegoprubart in patients with IgAN is underway.

Methods

42 adults with biopsy proven IgAN and proteinuria ≧0.75g/24h will be enrolled into 2 sequential open-label cohorts assessing the efficacy of 10mg/kg and 5mg/kg of tegoprubart administered IV every 3 weeks. The cohorts are staggered such that the 5mg/kg cohort will not proceed if futility is seen with the 10mg/kg cohort. The cohorts have the same inc/exc criteria, visit schedule and endpoints. The primary endpoint is change from baseline of urine protein to creatinine ratio after 24 weeks of therapy. The study will continue through Week 96 to assess change in eGFR.

Results

The study design includes interim analyses for futility after 12 subjects in each cohort complete 24 weeks. Futility in the 10mg/kg cohort would end the trial. Futility in the 5mg/kg cohort, would result in termination of that cohort only. Results will be presented for each cohort’s interim analysis, when each cohort completes weeks 24 and 96.

Conclusion

Inhibition of CD40L has potential as a treatment for IgAN. This Phase 2 trial will assess 2 doses of tegoprubart in patients with IgAN, evaluating the drug’s ability to reduce proteinuria and prevent decline in eGFR.

Funding

  • Commercial Support