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. 2023 Sep 25:36:11951.
doi: 10.3389/ti.2023.11951. eCollection 2023.

Qualifying a Novel Clinical Trial Endpoint (iBOX) Predictive of Long-Term Kidney Transplant Outcomes

Amanda Klein  1 , Alexandre Loupy  2 , Mark Stegall  3 , Ilkka Helanterä  4 , Luke Kosinski  1 , Eric Frey  1 , Olivier Aubert  2 , Gillian Divard  2 , Kenneth Newell  5 , Herwig-Ulf Meier-Kriesche  6 , Roslyn Mannon  7 , Thomas Dumortier  8 , Varun Aggarwal  1 , Jagdeep T Podichetty  1 , Inish O'Doherty  1 , Ahmed Osama Gaber  9 , William E Fitzsimmons  1
Affiliations

Qualifying a Novel Clinical Trial Endpoint (iBOX) Predictive of Long-Term Kidney Transplant Outcomes

Amanda Klein et al. Transpl Int. .

Abstract

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies.

Keywords: iBox; kidney transplant; organ transplant; transplant clinical trial; transplant outcomes.

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Conflict of interest statement

AK, LK, EF, and VA are employed by C-Path. AL holds shares in Cibiltech. IH holds research funds from MSD and Hansa Biopharma, receives consultancy honoraria from Hansa Biopharma, MSD, Novartis, and Takeda, is an associate editor for American Journal of Transplantation, and is a Coordinating Committee member of TTC. H-UM-K is employed by Veloxis Pharmaceuticals. KN serves as a scientific advisory board member for Angion, Care Dx, CSL Behring, Hansa Biopharma, Immucor, Novartis, Sangamo Therapeutics, Sanofi, Takeda, Talaris, and Viela Bio. RM is employed by University of Nebraska Medical Center; serves as a consultant for Chinook Therapeutics and Olaris Inc; holds research funding from Transplant Genomics, Inc and Verici DX; has received honoraria from CSL Behring; holds patents or royalties with Eurofins; has an advisory or leadership role with Vitaerris VKTX01 IMAGINE Trial and Verici Dx; and is Chair, ASN Policy and Advocacy Committee; Immediate Past-Chair, Women in Transplantation; Member, ASN Grants Committee; Chair, SRTR Review Committee; Member, DSMB, NIDDK/NIH; and Deputy Editor, American Journal of Transplantation. AG receives research funding from Hansa Biopharma, Veloxis Pharmaceuticals, Novartis, and Medeor Therapeutics. WF serves on the Board of Directors of CTI Clinical Trial Services; is Adjunct Professor at University of Illinois at Chicago; is founder of Tutela Pharmaceuticals; and serves as a consultant to Azoth Immune Medicines, Tract Therapeutics, and Veloxis Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Critical Path Institute’s Transplant Therapeutics ConsortiumGovernment and Regulatory Agencies • National Institutes of Health • U.S. Food and Drug AdministrationAcademic Institutions • Charité – Universitätsmedizin Berlin • Helsinki University Hospital • Hospital do Rim • Houston Methodist Hospital • Katholieke Universiteit Leuven • Mayo Clinic • Necker Hospital, Paris Transplant Group • University of Colorado, Denver • University of Wisconsin, School of Medicine • University of ManitobaProfessional Societies • American Society of Transplantation • American Society of Transplant Surgeons • The European Society for Organ Transplantation • The Transplantation SocietyBiopharmaceutical Industry and Diagnostic Companies • argenx • Bristol Myers Squibb • CareDx • CSL Behring • Eledon Pharmaceuticals • Eurofins Transplant Genomics • Hansa Biopharma • Immucor • Novartis • Sanofi • Takeda Pharmaceutical Company Limited • Talaris Therapeutics • Thermo Fisher Scientific Incorporated • Veloxis PharmaceuticalsAdditional Acknowledgments:• Anat Tambur• Klaus Romero• Byron Smith• Lauren Quinlan• Cecile Olivier• Mark Haas• Christina Higgins• Mike Pauley• Christine Miller• Nicholas King• Devrim Eren• Nicole Spear• Erin Beach• Patrick Lang• Grace Erhart• Rhoda Muse• Hailey Davenport• Sarah David• Howie Gebel• Stephen Karpen• Jackson Burton• Stephen Piccoli• John Holman• Zihan Cui• Kitty Bogy

Figures

FIGURE 1
FIGURE 1
Regulatory timeline with FDA and EMA. CPIM, Critical Path Innovation Meeting; EMA, European Medicines Agency; FDA, Food and Drug Administration; IR, information request; LOI, letter of intent; QO, qualification opinion; QP, qualification plan; RLSE, reasonably likely surrogate endpoint.
FIGURE 2
FIGURE 2
Flow diagram of the data selection process. COU, context-of-use; RCT, randomized controlled trial; TTC, Transplant Therapeutics Consortium.
FIGURE 3
FIGURE 3
Density of time points where iBOX assessments were made (y-axis), compared with the time posttransplant (x-axis) out to 8 years, as shown in [7].
See this image and copyright information in PMC

References

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