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
- 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.