Ampio updates phase III, multicenter, double-blind STEP study of Ampion for knee osteoarthritis

Ampio Pharmaceuticals, Inc. (NYSE MKT: AMPE) today announced an update on the phase III, multicenter, double-blind STEP study of Ampion™ for osteoarthritis of the knee.

The STEP study enrolled 538 patients, 269 patients received Ampion™ and 269 patients received saline vehicle control. There were two primary endpoints: 1. Efficacy in reducing pain, as measured by the WOMAC A pain subscore and 2. Safety of Ampion™ as measured by adverse events (AEs). The WOMAC C Function subscore was examined as a secondary endpoint. Changes in pain and function from baseline between Ampion™ and saline treatment groups were analyzed using a mixed model, adjusted for baseline score. Safety was examined in the safety dataset while efficacy was analyzed in the per-protocol (PP) population, in which patients met all entry criteria and had no major protocol deviations. There were 475 patients included in the PP population (242 received Ampion™ and 233 received saline vehicle control).

Review of the data from the STEP study confirmed that 382 (72%) patients received study medication that had fallen below the product specification temperature range. The average length of exposure below this temperature range was 16.1 hours (maximum: 36.3 hours). This technical difficulty was out of the control of Ampio (Sponsor) and affected our ability to perform the statistical analysis according to plan. We believe the temperature deviations that were present in the 72% of patients likely affected the level of active ingredients in the injected dose of Ampion™. Despite this difficulty efficacy was demonstrated in patients with the most severe form of OA (KL IV, where the number of patients was sufficient for statistical analysis) for which the only current alternative therapy is knee joint replacement.

The company plans to present safety data From the Australian phase I and Phase II studies as well as the SPRING, STEP and Multiple Injections studies for the BLA. Efficacy data for the BLA will be drawn from the SPRING and Multiple Injections Study. The company plans to submit the BLA before the end of Q1 2015.

Efficacy:

Although the majority of patients received study drug that had fallen below recommended temperature ranges, some important information on the efficacy of Ampion™ could be gleaned from this trial.

• The treatment effect differed based on the temperature excursion from the recommended range (interaction p < 0.001). Patients receiving study drug with temperature excursions had varying treatment effects depending on the lowest temperature that was reached during transport of the study drug.
• There was a significant interaction observed between OA severity, as measured by Kellgren-Lawrence grade, and treatment effect (interaction p < 0.001). The strongest effects of Ampion™ were observed in the patients with severe OA of the knee (Kellgren-Lawrence grade IV, KL IV), for which there are no current drug therapies available:
  • Over one-third of patients enrolled were Kellgren-Lawrence grade IV (n=185).
  • The change in WOMAC A Pain from baseline to week 20 for all 185 KL IV patients, inclusive of temperature excursions, was trending towards significantly greater reductions in pain following treatment with Ampion™ (-0.86), than that of saline vehicle control (0.66), p = 0.08. The change in WOMAC C Function from baseline to week 20 was also trending towards significantly greater improvements in function following treatment with Ampion™ (-0.84), than that of saline (-0.64), p = 0.07.
  • In KL IV patients with temperature excursions (134 patients), significantly greater reductions in pain were reported following treatment with Ampion™ (-0.85) compared to saline (-0.58), p = 0.04. Likewise, there was a significantly greater improvement in function following treatment with Ampion™ (-0.87) compared to saline (-0.59), p = 0.03.

Safety:

• Overall, there were 249 adverse events (AEs) reported: 118 (44%) in Ampion™ and 131 (49%) in Saline control.
  • The most common AE was arthralgia (joint pain), reported in 13% and 11% in the patients treated with Ampion™ and saline, respectively.
  • The majority of AEs were of minor severity (118 events, 47%), followed by moderate (115 events, 46%) and severe (16 events, 6%). Minor, moderate, and severe adverse events were similar in patients treated with Ampion™ (24%, 22%, 3%, respectively) compared to saline (20%, 21%, 3%).
• No serious adverse events (SAE) were reported related to study drug.