Clinical Trials
Voclosporin
Psoriasis Clinical Trials
Combined European/Canadian Phase 3 (ESSENCE) Trial
The first patient was enrolled in ESSENCE trial on December 3, 2006. On July 20, 2007, the Company closed recruitment of the ESSENCE trial at 642 patients. The patient population comprises 231 Canadian patients, 295 patients from Germany and 116 patients from Poland. The ESSENCE trial is currently being performed at a total of 50 centers in Germany, Poland and Canada. It is expected that the final data from this trial will be released in the first quarter of 2009.
On March 31, 2008, the Company announced that an independent data monitoring committee (DMC) met and reviewed the interim data from the ongoing blinded ESSENCE trial. The review included 24-week data from approximately 50% of the patients enrolled in the trial. Based on their review of the safety and efficacy data, the DMC did not raise any concerns that would require a change to the original study design.
This is the first direct comparison trial versus cyclosporine (current European standard of care) in moderate to severe psoriasis.
Canadian Phase 3 Trial
The Canadian Phase 3 trial which commenced on December 2, 2004 was designed to investigate voclosporin in patients suffering from moderate to severe psoriasis over a 24-week period. Equal numbers of patients were randomized to one of the four treatment groups. This double blind trial examined the efficacy of 3 dosing groups of voclosporin (0.2 mg/kg, 0.3 mg/kg and 0.4 mg/kg twice daily) over a 24-week period compared to placebo. Subsequent to the first 12 weeks, those patients who received placebo were administered the mid-dose of 0.3 mg/kg twice daily for the remaining 12 weeks of the study. Patients who received active treatment with voclosporin remained in their respective dosing groups for the final 12 weeks of the trial.
The primary endpoint being investigated was the number of patients achieving a 75% decrease in the Psoriasis Area and Severity Index (PASI) score at 12 weeks. Secondary endpoints of the trial included maintenance of stable kidney function and assessment of quality of life.
The Company announced final safety and efficacy data October 5, 2006. A summary of the results is as follows:
Patients have now received continuous treatment with voclosporin for a total of 60 weeks. Over the course of the 24-week Phase 3 trial, patients exhibited a 60% mean improvement in Psoriasis Area and Severity Index (PASI) scores. After an additional 36 weeks of treatment, there was a 54% mean improvement in PASI scores indicating continued therapeutic benefit. This beneficial effect was still observed twelve weeks after discontinuing voclosporin treatment; mean PASI scores remained at 35% below pre-treatment scores.
Subsequent to 60 weeks of continuous treatment, there were no clinically significant changes in kidney function, cholesterol, triglycerides, new onset diabetes, infectious complications, or other laboratory parameters. This supports the long term safety of voclosporin.
Kidney Transplantation (PROMISE) Trial
The Company announced successful completion of the PROMISE trial on May 27, 2008. An extension to the six month trial is currently being performed at forty-two centers across North America, including thirty-eight centers in the United States and four centers in Canada. Patient enrolment was completed on June 26, 2007.
A total of 334 de novo (newly transplanted) kidney transplant patients have been enrolled in this trial. Patients were placed into one of four separate treatment groups; three different dose groups of voclosporin (0.4 mg/kg, 0.6 mg/kg, and 0.8 mg/kg twice daily) compared with the fourth group, a tacrolimus (0.05 mg/kg twice daily) control arm. Patients in all four treatment groups had their doses adjusted in order to achieve pre-defined blood levels of either voclosporin or tacrolimus. All patients received oral treatment of the drug (voclosporin or tacrolimus) over a six month period, along with other standard immunosuppressive therapies used following transplantation.
On January 3, 2008, the Company announced that the last patient enrolled completed the six month trial. On June 2, 2007, and August 2, 2007, the Company announced that it had received permission from Health Canada and the Food and Drug Administration (USA), respectively, to allow patients to remain on voclosporin until the drug is commercially available.
The primary endpoint of the trial is defined as non-inferiority in biopsy proven acute rejection (BPAR) episodes in patients receiving voclosporin for six months as compared to the tacrolimus control. Additionally, kidney function and other laboratory parameters such as hypertension, hyperlipidemia and new onset diabetes mellitus will be monitored for the duration of the trial. The overall goal of the trial is to find the most appropriate dose that will result in efficacy (lack of rejection) with minimal side effects. The use of the other two calcineurin inhibitors, cyclosporin and tacrolimus, are often associated with significant safety concerns.
Phase 2 Psoriasis Study Conclusion: The trial demonstrated that voclosporin was well tolerated and efficacious. The results showed that voclosporin met or exceeded all of the primary and secondary efficacy and safety endpoints of the study.
Phase 2a Renal Study Conclusion: The trial showed positive results and demonstrated that voclosporin was well tolerated and efficacious. All primary and secondary endpoints of the study were achieved.
Uveitis Clinical Trial
Isotechnika's partner, Lux Biosciences, initiated pivotal trials of voclosporin in uveitis in February, 2007. The pivotal trial program, which consists of three controlled, double masked Phase 2/Phase 3 trials, is investigating the use of voclosporin (referred to as LX211 by Lux) in different forms of active uveitis in addition to maintenance of quiescent disease.
Lux has been granted orphan drug designation from the FDA for voclosporin for the treatment of non-infectious posterior, intermediate, and panuveitis. This designation qualifies Lux for exclusive marketing rights in the United States for seven years if the company is the first to receive marketing approval. Furthermore, the European Agency for the Evaluation of Medicinal Products (EMEA) committee for Orphan Medicinal Products has adopted a positive opinion on orphan medicinal product designation for voclosporin for the treatment of chronic, non-infectious uveitis.
On August 7, 2007, Lux and Isotechnika announced that the FDA granted Fast-Track designation for voclosporin for the treatment of uveitis.
Lux Biosciences has received regulatory approval to commence their clinical trials in Austria, Canada, France, Germany, India, United Kingdom and the United States.Drug-eluting Coronary Stents Trial
Our partner, Atrium Medical Corporation, recently received approval from the Belgian Competent Authority to investigate voclosporin as the drug utilized in the CINATRA TM Drug Coated Coronary Stent system.
Atrium began enrollment for the CONFIRM1, First-in-Man (FIM) trial on June 9, 2008. This is a prospective, multi-center, single blind, randomized, controlled study using the CINATRATM voclosporin coated coronary stent system, which will be compared to Atrium's CINATRATM bare metal coronary stent (BMS) platform. This first use study of voclosporin on an implantable medical device will enroll 100 patients, and will be conducted at seven hospitals in Belgium with Glenn Van Langenhove, MD, PhD of Middelheim Hospital, Antwerp, as the study's Principal Investigator.
The primary endpoint of the trial is to evaluate the safety and performance of the CINATRATM voclosporin coated coronary stent system in patients with de novo coronary artery disease. Patient outcomes, in addition to drug coated stent performance, will be assessed by measuring Late Lumen Loss, in-stent and in-segment Lumen Loss measurements at six months following implantation.