PHOENIX phase III trial of PHP for distributive shock to continue after positive midpoint recommendation from DMB

The PHOENIX trial is a European, placebo-controlled, Phase III study treating catecholamine-resistant patients in distributive shock with the Nitric Oxide (NO) scavenger Pyridoxalated Haemoglobin Polyoxyethylene Conjugate (PHP). The study was launched by Curacyte AG in Austria, Belgium, Germany, Spain, The Netherlands and in the United Kingdom in 2009.

Today the successful completion of the second interim analysis on safety and mortality data of 50% of the study population in the trial is reported. Statistical results were reviewed in an unblinded fashion by an independent Data Monitoring Board (DMB). The DMB, consisting of intensive care physicians, bioethical experts and statisticians from the US and Europe came to the conclusion, that the study should be continued without change.

The continuation of the PHOENIX study represents encouraging news for the management of critically ill patients suffering from catecholamine-resistant distributive shock for whom satisfactory treatment options are currently lacking. The trial is designed to statistically demonstrate survival benefit for patients treated with PHP after 28 days compared to placebo (+ standard care), and at day 60 and day 90 as secondary endpoints.

In interpretating the DMB’s recommendation, it can be concluded that the overall safety profile of the company’s lead product PHP appears acceptable without signals or trends which might require modification or suspension of the trial. Consequently, the pivotal study will be continued according to the plan with the following key milestones:

To date more than 300 of the 454 target patients have been enrolled in the study. The next step will be the last interim analysis on 75% of the patients envisaged in Q4/2011 and the completion of recruitment by the end of 2011. Final top-line results are likely to be available in Q2 / 2012.

Scientists from Apex Bioscience, Inc. (Chapel Hill, North Carolina), Curacyte’s wholly-owned US subsidiary, have developed the modified haemoglobin product with the intention to exploit the natural NO-scavenging and metabolizing properties of haemoglobin. There is compelling evidence that NO is responsible for vasodilation and hypotension in distributive shock. In the successfully conducted Phase II clinical development program PHP has previously been demonstrated to reverse vasodilation and resolve hypotension associated with this form of shock.

About the PHOENIX trial
This Phase III, multi-center, randomized, placebo-controlled study compares the effectiveness of continuous infusion of PHP plus conventional vasopressor therapy against placebo (normal saline) plus conventional vasopressor therapy in patients with catecholamine-resistant distributive shock. In addition, the safety and tolerability of this new treatment modality will be evaluated.

For inclusion into the trial the patients must be adequately resuscitated with fluids and must require a norepinephrine dose of ≥0.3 mcg/kg/min to maintain a mean arterial blood pressure of ≥ 65 mmHg. Furthermore, patients must at least fulfill two criteria indicative of a systemic inflammatory response (“SIRS” criteria). PHP as active compound or placebo will be administered by continuous intravenous infusion at 0.25 ml/kg/hr for a maximum of 150 hours.

Efficacy will be demonstrated by PHP significantly reducing 28-day all-cause mortality. Secondary endpoints will include: Survival time, survivor days in the intensive care unit (“ICU”) and time on mechanical ventilation and on vasopressors.

The trial is being conducted in 72 hospitals in six European countries and led by Prof. Jean-Louis Vincent from the Erasme University in Brussels as the coordinating principal investigator in Europe.