Osiris Therapeutics, Inc., reported today that its multi-center, randomized, controlled clinical trial comparing the safety and effectiveness of Grafix® to standard of care in patients with chronic diabetic foot ulcers had met the pre-specified stopping rules for overwhelming efficacy as determined by the data monitoring committee during a planned interim analysis.
For the primary endpoint, 62% of patients receiving Grafix had complete wound closure compared to only 21% (p<0.0001) of patients who received conventional treatment for their wounds - a relative improvement of 191% and the largest ever reported from such a study.
A total of 131 patients were enrolled with the interim analysis being conducted on the first 97 to complete the trial.
MORE ABOUT THE TRIAL:
The trial also reached statistical significance in favor of Grafix on all top-line secondary endpoints, demonstrating faster wound closure and a reduction in the number of treatments needed to achieve wound closure.
In the crossover phase of the trial, patients whose wounds failed to close after 12 weeks of standard of care had an 80% closure rate when switched to Grafix. Importantly, patients randomized to receive standard of care were 74% more likely to experience an adverse event than those receiving Grafix (p=0.008). As a result, the blinded phase of the trial is being discontinued immediately and all patients randomized to the control arm will be offered treatment with Grafix.
"Today, Osiris has established a new standard in diabetic wound care and has demonstrated to the world the tremendous impact stem cell products can have in medicine," said C. Randal Mills, Ph.D., Chief Executive Officer.
"Diabetic foot ulcers afflict 25% of all diabetics and are responsible for more hospitalizations than any other diabetic complication. With 25 million diabetics in the United States, the cost to our health care system is enormous. Through this rigorous study we have shown that Grafix can heal more patients, in less time, and with fewer complications."
"These data points are very compelling as we have not had a new cellular therapy for diabetic foot ulcers in over 10 years," said Dr. Larry Lavery, Principal Investigator and Professor of Plastic Surgery, University of Texas Southwestern Medical Center. "Compared to other similarly designed studies, this trial demonstrates, by far, the largest relative improvement in complete wound closure. This is great news for our patients with diabetic foot ulcers that are at such high risk of losing their legs."
WHAT IS GRAFIX?
Grafix is a human cellular repair matrix that provides a high-quality source of living mesenchymal stem cells (MSCs). It is a flexible, conforming membrane that is applied directly to acute and chronic wounds.
"We know now that an unfortunate consequence of diabetes is the pathological change that occurs with the number and functionality of certain stem cell populations necessary for optimal wound repair," said Michelle LeRoux Williams, Ph.D., Chief Scientific Officer. "With Grafix, we are able to help correct this problem by providing patients with a rich source of healthy, non-controversial stem cells contained within a biologic matrix for easy delivery in the out-patient setting."
Osiris partnered with CPC Clinical Research, an Academic Clinical Research Organization (CRO), who was responsible for all clinical monitoring, data management, and biostatistics services.
"One key aspect of an academically led CRO is our credible scientific oversight and quality control during the execution of the trial," said William R. Hiatt, M.D., President of CPC and Professor of Medicine, Division of Cardiology, Department of Medicine, University of Colorado School of Medicine. "This is one of the most rigorous wound care trials conducted, enhanced by our proprietary wound core lab technology which is able to independently assess wound closure in a blinded manner."
About the Trial (Protocol 302)
Protocol 302 is a single-blind, randomized, controlled multi-centered trial is evaluating the efficacy and safety of weekly applications of Grafix for the treatment of chronic diabetic foot ulcers.
A total of 131 patients were enrolled at 19 leading wound care centers across the United States. Patients between 18 and 80 years of age with confirmed type 1 or type 2 diabetes and chronic diabetic foot ulcers on the dorsal or plantar surface of the foot were randomized to Grafix or control dressings at a 1:1 ratio. Ulcers had to be present for at least 4 weeks prior to randomization and be between 1 cm2 and 15 cm2 in size. Patients were excluded from the trial if the ulcer decreased with more than 30% during the one week screening period.
Patients received treatment weekly for up to 12 weeks. The primary endpoint measures complete wound closure by 12 weeks as determined by the investigator and confirmed by an independent, blinded Wound Core Lab. Secondary endpoints include complete wound closure rates for those patients that complete all scheduled treatments, time to wound closure, number of applications, proportion of patients achieving at least a 50% reduction in wound size by day 28 and number of re-occurrences. Patients randomized to the control group who did not heal within 12 weeks entered a cross-over arm for evaluation in an additional 12 week open-label treatment with Grafix.