The U.S. Food and Drug Administration has granted permission to begin a Phase III study with HuMaxTM-CD4 to treat patients with active rheumatoid arthritis (RA) who have failed to respond to treatment with methotrexate and TNF-alpha blocking agents. These patients represent a major unmet medical need, as they do not have an effective treatment option.
The objective of the Phase III trial is to confirm the safety and efficacy of HuMax-CD4 in the treatment of RA. The study will enroll 400 patients who will be treated with either 80 or 160 milligrams of HuMax-CD4 or placebo for a total of 26 weeks. The patients will be given two doses, two weeks apart, followed by one dose each month. The Phase III trial will be initiated in the US and Europe in December 2001, and is planned to take place at over 50 locations.
HuMax-CD4 is a high affinity fully human antibody that targets the CD4 receptor on T-lymphocytes. These cells are involved in promoting autoimmune disease and an antibody that targets them can be used for the treatment of several inflammatory diseases including rheumatoid arthritis and psoriasis. HuMax-CD4 has been studied in both Rheumatoid Arthritis (RA) and Psoriasis clinical trials.
In previous studies, HuMax-CD4 was reported safe and well tolerated. In a Phase I/II RA study, fifty percent of the treated patients in the four highest dose cohorts, achieved favorable responses to the antibody as measured by objective criteria defined by the American College of Rheumatology (ACR). They achieved responses ranging from ACR 20 to ACR 70.
The dose response observed in the Phase I/II RA study correlates with the initial results of the HuMax-CD4 Phase II dose finding study in psoriasis patients, where the antibody has shown a statistically significant dose response. In addition, mean Psoriasis Area Severity Index (PASI) score was reduced in all treatment groups with a 30% difference between the placebo and 160mg dose groups. HuMax-CD4 was also safe and well tolerated.
The psoriasis trial was a small placebo controlled Phase II study designed to establish the safety and lowest effective dose of HuMax-CD4 in patients with moderate to severe psoriasis. Patients received either one of four dose levels or placebo weekly for four weeks. Eighty-five patients were followed for a total of 16 weeks and final results of the study will be presented early next year.