Cambridge Antibody Technology (CAT) and Genzyme Corp announce preliminary results from a Phase I/II clinical trial of CAT-192, a human anti-TGFß1 monoclonal antibody. The primary objective of the trial was to assess the safety, tolerability and pharmacokinetics of CAT-192 in patients suffering from diffuse systemic sclerosis. The secondary objective was to evaluate the potential clinical outcomes for any future trial in systemic sclerosis.

The double-blind, placebo-controlled trial enrolled 45 patients at 12 medical centres in the US and Europe. Patients were randomised to receive one of three dose levels of CAT-192 (0.5mg/kg, 5 mg/kg or 10 mg/kg) or matching placebo, given as an intravenous infusion every six weeks for four doses.

Preliminary results show that the primary objective was met; CAT-192 was generally safe and well-tolerated at each dose level. Elimination half-life was consistently around three weeks. There were no treatment-related serious adverse events observed. Four patient deaths occurred during the trial and were determined by independent medical reviewers to be attributable to patients' underlying disease, and unrelated to treatment.

For the secondary objective of the trial a number of clinical endpoints and biological markers, potentially indicative of disease progression, were evaluated. Preliminary review of these markers indicated that disease duration and gender played important roles in the results, and that the placebo group's skin score did not deteriorate during the trial as anticipated. Given these factors and the small sample size, no definitive conclusions regarding the efficacy of CAT-192 can be drawn at this time. Additional analyses and alternative trial designs are being evaluated.

"The clinical development teams from both companies are encouraged by the safety and pharmacokinetic results seen in this trial," said Dr David Glover, chief medical officer at Cambridge Antibody Technology. "We have gained useful insights that will help determine the next steps in our clinical development programme. We will continue to evaluate the data, and to work with scleroderma experts to determine how to progress in the future."

"We are continuing our efforts to target TGFß through a variety of human monoclonal antibodies, an approach that we believe has great potential in the development of effective therapies for scleroderma and other fibrotic diseases," added Dr Richard Moscicki, Genzyme's chief medical officer.

The companies expect that the results of the trial will be submitted for presentation at a major scientific conference later this year.

Diffuse systemic sclerosis, a form of scleroderma, is a chronic, life-threatening disorder caused by the production of excess collagen, which leads to scarring of the skin and internal organs. Eighty per cent of those affected by this disease are women between the ages of 25-55. About 40 per cent of all patients with this disorder die within ten years of diagnosis. There is currently no effective therapy for the disease, which affects an estimated 300,000 people worldwide.

Genzyme and CAT have been working in partnership to develop and commercialise human TGFß monoclonal antibodies for the treatment of diffuse systemic sclerosis since September 2000.