Capstone presents AZX100 Phase 2a trial results for keloid and trocar site scarring

Dec 14 2010

Capstone Therapeutics announced today twelve-month results from its two AZX100 Phase 2a pilot clinical trials in keloid scarring and seven-month interim results of its ongoing AZX100 Phase 2a pilot clinical trial in surgical (trocar site) scarring.

The goals of a Phase 2a clinical trial include assessments of the safety and tolerability of the therapeutic agent being tested, initial investigation of dose and administration schedules and analyses to detect any signal or trend of efficacy in the chosen indication.

AZX100 Phase 2a in Keloid Scarring - Study Description

Keloid scars are among the most difficult dermatologic conditions to treat, and there are no currently-approved therapeutic agents specifically indicated for these scars. "Preventing development of a keloid after surgery is a real challenge. I don't know a reliable way to routinely do it," said Mark V. Dahl, MD, former President, American Academy of Dermatology and a consultant to Capstone.

Capstone conducted two pilot Phase 2a clinical trials of AZX100 in reduction or prevention of post-excision keloid scarring: OL-ASCAR-04, with dosing at 3.0 mg or 10.0 mg per linear cm; and OL-ASCAR-05, with dosing at 0.3 mg or 1.0 mg per linear cm. In these trials, AZX100 (or placebo) was administered 21 and 42 days following surgery, with no additional dosing throughout the remainder of the trial. These were blinded, placebo-controlled, multicenter, parallel group dose ranging studies to evaluate the safety and preliminary efficacy of AZX100 following excision of keloid scars.  Fifty-nine subjects were dosed in each of these two pilot keloid scarring trials.

Pre-specified endpoints of these studies included evaluations of safety and efficacy of AZX100 based on the subjective primary endpoint Patient and Observer Scar Assessment Scales (POSAS) and objective secondary endpoints analyzed using 2D and 3D high-resolution digital photography.  These endpoints included blinded, independently-scored Visual Analog Scales (VAS) and objective measurements of scar dimensions. Each of the endpoints of these trials was being evaluated for its potential to guide and inform future studies of AZX100 in dermal indications.

Twelve-Month Results

• The primary endpoint of the Phase 2a pilot keloid scarring trials was the Month 12 score on the subjective POSAS. The trials did not meet the study objective of demonstrating statistically-significant efficacy based on differences in this scale between AZX100 and placebo at the single Month 12 time point.
• Secondary endpoints, including earlier monthly POSAS scores, VAS scores and objective endpoints based on high resolution digital photography, showed multiple signals of AZX100 efficacy within the1.0 mg-per-linear-cm cohort, particularly at earlier time points (e.g. between Months 2 and 9, depending upon the metric.) No meaningful benefit was observed for the other AZX100 doses (0.3 mg, 3.0 mg or
  10.0 mg per linear cm).
• There was a consistent pattern favoring AZX100 treatment (1.0 mg per linear cm) across multiple outcomes and time points; but, with a small sample size>
• The safety profile of AZX100 was determined to be favorable.

AZX100 Phase 2a in Surgical (Trocar Site) Scarring - Study Description

The Company is also conducting - with similar outcome measures - a pilot Phase 2a clinical trial of AZX100 in surgical (trocar site) scarring (OL-ASCAR-03); this is a double-blind, placebo within-patient controlled, multi-center dose ranging study to evaluate the safety and preliminary efficacy of AZX100 (3.0 mg or 10.0 mg versus placebo) in trocar site scars of subjects who have undergone arthroscopic shoulder surgery. In this trial, AZX100 (or placebo) was administered 9 and 21 days following surgery, with no additional dosing throughout the remainder of the trial.

One hundred fifty subjects were dosed in the trocar site scarring trial. Twelve-month data from this study are due 1Q2011.

Seven-Month Interim Results

The limited seven-month interim analysis of the Phase 2a pilot surgical (trocar site) scarring trial showed a favorable safety profile and revealed multiple signals of AZX100 efficacy, more often within the 3.0 mg trocar sites than within sites receiving 10.0 mg.  Most AZX100 treatment effect at 3.0 mg was seen at time points earlier than Month 7; e.g., Scar Total Volume at Month 3 (p = 0.047) and Scar Length at Month 5 (p = 0.034).

Because the study is ongoing, it is not yet possible to determine whether additional statistically significant effects will be observed.

Commentary

"We designed these Phase 2a pilot clinical trials to guide the future development of AZX100 in multiple scarring indications. The favorable safety profile and the observed efficacy signals support our belief that AZX100 is a viable candidate in dermal scar reduction," said Randolph C. Steer, MD, PhD, President of Capstone Therapeutics. "The pattern of AZX100 efficacy at 1.0 mg per linear cm at earlier time points that was seen in the keloid trial will assist us in future dose and administration optimization clinical trials."

"We believe the AZX100 clinical data merit its continued development," said Jock Holliman, Executive Chairman of Capstone Therapeutics. "Based on the results obtained thus far from these Phase 2a pilot clinical trials, Capstone will seek a collaboration partner to advance AZX100 in both surgical and keloid scar reduction."

Source: Capstone Therapeutics