News
Reports Phase 2 Data On CRx-150 In Human Inflammatory Disease Model; Periodontitis Trial Fails Main Goal
Cambridge, Mass.--(Business Wire)--CombinatoRx, Incorporated (NASDAQ: CRXX - News) today announced preliminary results of its randomized, blinded, placebo-controlled clinical trial of CRx- 150 in patients with periodontitis, a chronic infectious disease with an inflammatory component, associated with elevation of systemic inflammatory markers.
This trial was designed to determine how immuno-modulating agents such as CRx-150 would affect various systemic inflammatory markers in individuals with periodontitis in both the acute and chronic phase of immunoinflammation. CRx-150 did not reduce C-reactive protein (CRP) in the chronic inflammatory phase, the primary endpoint of the trial, as measured at day 42 prior to SRP. CRx-150 did reduce CRP in the acute inflammatory phase compared to placebo (p = 0.026), a secondary endpoint of the trial, as measured on day 43 of treatment and within 24 hours following scaling and root planning (SRP) of a subject's teeth. Analysis of the effect of CRx-150 on immuno-inflammatory cytokines, another set of secondary endpoints, demonstrated that the CRx-150 treated group also exhibited a non-statistically significant trend towards reduced acute release of TNF-a and IL-6 within 24 hours after SRP as compared to the placebo group. There were small or no differences between CRx-150 and placebo for the other inflammatory markers measured including IL-1, IL-8, IL-12 and IFN-gamma. CRx-150 was generally well tolerated and there were no serious adverse events reported. The most common adverse event in the study reported as related to the CRx-150 treated group was headache, a known side effect of dipyridamole.
Data from this CRx-150 trial are being presented in a poster entitled "Effects of CRx-150 on Chronic and Acute Release of Inflammatory Markers in Patients with Periodontitis, a Randomized Placebo-Controlled Clinical Trial", F. D'Aiuto, etal., at the Gordon Research Conference on Periodontal Diseases, June 4-9, 2006 in Barga, Italy.
"By blunting the spike in CRP that occurs immediately following SRP, CRx-150 has demonstrated its ability to effectively modulate the release of an important validated inflammatory marker," said Dr. Jan Lessem, Chief Medical Officer of CombinatoRx.
"Further study of CRx-150 will be required to understand the magnitude of its effects, given the activity in the acute phase of this model, and we look forward to results of the CRx-150 Phase 2 trial in patients with rheumatoid arthritis expected in the first half of 2007," commented Alexis Borisy, President and CEO of CombinatoRx. "Overall we are very pleased that four of the six trials on which we have reported Phase 2 data this year have now shown translation of activity into humans."
About the Trial Design
This clinical trial was a blinded, placebo-controlled, randomized study of the effect of an 8-week treatment of CRx-150 compared to placebo in a 1:1 ratio. The primary endpoint was a reduction in CRP from baseline to day 42. Secondary endpoints of the study included changes in CRP levels following SRP, reduction in periodontal pocket depth and ability to modulate a panel of inflammatory cytokines.
Patients were enrolled into the trial with severe periodontitis, defined as a minimum of 10 pockets between the teeth and gum measuring greater than or equal to 5mm in depth with at least 4 pockets greater than or equal to 6mm. Ten percent of all the pockets must have been shown to bleed on probing. Baseline CRP levels upon enrollment had to be greater than 1.5mg/L. Overall median CRP levels at study baseline were 3.4 mg/L. CRx-150 was dosed in this trial using a single dose of dipyridamole and two different doses of amoxapine. Patients received the first ratio for the first two weeks of treatment and the second ratio for the following six weeks. SRP of the subjects' teeth was conducted on day 42. Inflammatory cytokine levels were measured periodically throughout the study. Fifty-six patients were enrolled in the trial at a single study center in London, England.
About CRx-150
CRx-150 is a novel orally available syncretic drug candidate in Phase 2 clinical development for immuno-inflammatory diseases. A syncretic drug comprises two compounds that are designed to act synergistically through multiple pathways to provide a novel therapeutic effect which neither component alone can achieve. CRx-150 contains low doses of amoxapine and dipyridamole, neither of which is indicated for the treatment of immuno-inflammatory disease on its own, but which have been shown in preclinical studies to act synergistically to modulate cytokine production. CRx-150 was discovered using the CombinatoRx combination High Throughput Screening (cHTS(TM)) technology and would be developed in a unique formulation for the treatment of immuno-inflammatory diseases.
CRx-150 is currently being evaluated in an ongoing Phase 2 clinical trial in patients with rheumatoid arthritis. CRx-150 is one of a portfolio of six product candidates that CombinatoRx is currently testing in Phase 2 clinical trials.