THE EFFECT OF TASOCITINIB (CP-690,550) ON THE INCIDENCE OF ACUTE REJECTION AND RENAL FUNCTION IN DE NOVO KIDNEY TRANSPLANT PATIENTS: 6-MONTH INTERIM ANALYSIS OF A PHASE 2B STUDY

NEW IMMUNOSUPPRESSIVE AGENTS

S. Busque¹, J. Eris², D. Abramowicz³, B. Nashan⁴, C. Legendre⁵, S. Vitko⁶, A. Mota⁷, N. Lawendy⁸, G. Chan⁹, F. Vincenti^10
1School Of Medicine, Stanford University, Palo Alto/UNITED STATES OF AMERICA, ², Royal Prince Alfred Hospital, Sydney/AUSTRALIA, ³, Hopital Erasme, Anderlecht/BELGIUM, ⁴Hepatobiliary And Transplant Surgery, University Medical Centre Hamburg - Eppendorf, Hamburg/GERMANY, ⁵, Université Paris Descartes & Hôpital Necker, Paris/FRANCE, ⁶, Institut Klinicke a Experimentalni Mediciny, Prague/CZECH REPUBLIC, ⁷, Hospitais da Universidade de Coimbra, Coimbra/PORTUGAL, ⁸, Pfizer, New London/UNITED STATES OF AMERICA, ⁹, Pfizer, New London/CT/UNITED STATES OF AMERICA, ¹⁰, UCSF, San Francisco/UNITED STATES OF AMERICA

Body: Introduction: Tasocitinib (CP-690,550) is an orally active Janus kinase inhibitor that suppresses intracellular signal transduction of multiple cytokines. Prior Phase 2A data suggested that JAK would be a viable target for clinical immunosuppression. Study A3921030 compared a CNI-free tasocitinib regimen with a CsA regimen in kidney transplant patients (KT pts). This report focuses on the findings on acute rejection and renal function at 6 months. Methods: A3921030 was a 12-month Phase 2B dose/exposure study in which de novo KT pts were randomized 1:1:1 to either CsA or 1 of 2 CP-690,550 groups: CP1 (starting dose 15 mg BID through month 6, then 10 mg BID) or CP2 (15 mg BID through month 3, then 10 mg BID). All pts received basiliximab induction, MPA (same dose in all groups, 2 g/day MMF or 1.44 g/day MPS), and corticosteroids. For this interim analysis, the primary efficacy endpoint was the 6-month incidence of either biopsy-proven acute rejection (BPAR) as read by the central pathologist, or “clinical BPAR”, defined as BPAR associated with an increase in Scr of ≥0.3 mg/dL and ≥20% from pre-rejection baseline. The co-primary safety endpoint was iohexol-measured GFR at month 6. Secondary endpoints of renal function included Scr and GFR estimated using various Scr-based equations. Results: Of 331 KT pts randomized, 321 received study treatments, with 39% of pts receiving living donor allografts. The 3 study groups were similar in baseline characteristics. There were more premature discontinuations of study treatment in the tasocitinib groups (25.5%, 40.0% and 40.5% for CsA, CP1 and CP2, respectively) but the number of pts who discontinued because of acute rejection was similar among the 3 groups. The 6-month acute rejection rates, GFR measured by iohexol serum clearance and Scr at Month 6 are shown in the table below:

	CsA (n=109)	CP1 (n=105)	CP2 (n=107)
6-month incidence of BPAR	18.6%	15.1%*	9.6%*
6-month incidence of clinical BPAR	8.9%	9.5%*	5.2%*
6-month incidence of locally diagnosed acute rejection	20.3%	18.1%	13.4%
6-month graft survival	96.2%	96.1%	96.1%
Mean measured GFR at Month 6, mL/min, MMRM	58.8	68.5 (p=0.01 vs. CsA)	74.0 (p<0.0001 vs. CsA)
Scr at Month 6, mg/dL	1.42	1.29	1.18

* Statistically non-inferior to CsA Estimated GFR calculated using the Nankivell, MDRD and Cockcroft-Gault equations were also higher in the CP groups than CsA at Month 6. Conclusions: In this 6-month interim analysis, KT pts randomized to CNI-free tasocitinib regimens had statistically non-inferior acute rejection rate and improved renal function as compared with CsA. Longer follow-up is required to confirm if these findings are sustained beyond Month 6. Further analyses based on these results as well as safety and tolerability findings are ongoing to identify the optimal tasocitinib dose regimen.

Disclosure: All authors have declared no conflicts of interest.