Treatment with QPI-1002, a Short Interfering (SI) RNA for the

Prophylaxis of Delayed Graft Function. V. Peddi,1 L. Ratner,2 M.

Cooper,2 O. Gaber,2 S. Feng,2 P. Tso,2 V. Bowers,2 R. Naraghi,2 K. Budde,2

  1. Polinsky,3 E. Squiers,3 S. Erlich,3 Study Investigators Group.2 1CPMC,

San Francisco, CA; 2Multiple Institutions; 3Quark Pharmaceuticals,

Fremont.

Introduction: Delayed graft function (DGF) can adversely affect deceased donor

renal transplant outcomes, particularly in recipients of expanded criteria donor

(ECD) kidneys. We report fi rst results of a large Phase 2 study with QPI-1002

(NCT#00802347), a siRNA that transiently suppresses p53 mediated apoptosis

and that was previously shown to improve outcomes after acute kidney injury

and renal transplantation in preclinical models. Methods: 332 patients (pts) were

randomized 1:1 to single dose QPI-1002, 10.0 mg/kg IV, or Placebo in doubleblind

fashion post-allograft reperfusion. DGF was defi ned as the need for dialysis

≤7 days post-transplant (Tx) (except for dialysis on Day 1 for hyperkalemia or

hypervolemia). Pts were prospectively allocated to 4 strata by donor type (ECD or

SCD) and preservation [cold-stored (CS) or machine-perfused (MP)]. Estimated cold

ischemia time (CIT)>26 hrs was required in all but the ECD/CS stratum. Results:

In 327 (164 QPI-1002; 163 Placebo) effi cacy-evaluable pts, mean age, %male,

%of African descent, pt weight, BMI, peak %PRA, prior transfusion status, HLA

mismatch, mean CIT and donor terminal serum creatinine, % with hypertension and

cause of death did not differ between groups (p=ns). Pre-Tx DGF risk was 35% in

QPI-1002 and 36% in Placebo pts (p=ns), in whom DGF occurred in 50 (30.9%)

and 60 (36.4%; p=0.349). In the largest stratum (ECD/CS, n=177), DGF rates were

27.3% and 39.3% for QPI-1002 (n=88) and Placebo (n=89), respectively (30.5%

relative reduction, p=0.111), mean duration of dialysis (13.4 vs 25.3 days) was shorter

(p=0.292), mean number of dialysis sessions (6.0 vs 11.2.) was lower (p=0.271); and

time-to-fi rst post-Tx dialysis (hazard ratio 0.626, log-rank p=0.045) and mean Day

30 measured (m)GFR (34.8 vs. 21.1 mL/min/1.73 m2, p=0.035) were signifi cantly

improved following QPI-1002. The overall safety profi le was consistent with that

expected in Tx recipients and similar in both groups. Conclusions: Treatment with

QPI-1002 resulted in a relative reduction of DGF and signifi cantly improved time

to fi rst dialysis and Day 30 mGFR in the largest stratum (ECD/CS) in this Phase 2

study. QPI-1002 may reduce the need for dialysis in ECDs, possibly due to increased

expression of p53 following reperfusion in older kidneys, as has recently been

demonstrated in preclinical studies.

DISCLOSURE: Budde, K.: Grant/Research Support, Quark Pharmaceuticals.

Polinsky, M.: Employee, Quark Pharmaceuticals, Inc. Squiers, E.: Employee, Quark

Pharmaceuticals, Inc. Erlich, S.: Employee, Quark Pharmaceuticals, Inc.