Abbott Laboratories has recently announced the expansion of its Immunology clinical trials program to include studies evaluating the potential of the first fully human monoclonal antibody, D2E7 (adalimumab), in juvenile rheumatoid arthritis (JRA) and Crohn’s disease. JRA and Crohn’s disease are autoimmune disorders in which a human protein, tumor necrosis factor-alpha (TNF-á), has been shown to cause abnormal immune responses. D2E7 is being studied in other inflammatory diseases because its mechanism of action specifically targets TNF-á.
D2E7 is currently under review by the U.S. Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) for the treatment of adult rheumatoid arthritis (RA).
Juvenile Rheumatoid Arthritis (JRA) Trial
D2E7 will be studied in a randomized, multicenter, double-blind Phase III clinical trial that will assess its safety and efficacy in patients with polyarticular juvenile rheumatoid arthritis (JRA). Patient responses will be measured by the American College of Rheumatology (ACR) Pediatric 30 score, which is a 30 percent improvement in JRA signs and symptoms such as the number of joints with active arthritis and loss of motion, assessment of pain and degree of disability.
“We’ve seen tremendous advances in the treatment of adult RA and studies in pediatric patients are critical to understanding the potential use of new treatments in children who are fighting destructive symptoms at a much younger age,” said Daniel Lovell, M.D., M.P.H., chairman, Pediatric Rheumatology Study Group and professor of Pediatrics, Cincinnati Childrens Hospital Medical Center. “This disease can be particularly troubling for children because of its impact on their ability to participate in activities with other children. The symptoms of JRA are similar to adult RA, including swollen and tender joints that if untreated may affect a child’s growth and development and lead to permanent joint destruction.”
While the symptoms may be mild in some children, the disease can be persistent, ultimately damaging joints by eroding bones and cartilage. As the most common form of juvenile arthritis, JRA strikes children 16 years of age or younger, and affects girls twice as often as boys.
A Phase II/III study has been initiated that will evaluate the safety and efficacy of D2E7 in the induction of clinical remission in subjects with Crohn’s disease. Clinical remission refers to patients who are not showing any symptoms of the disease following treatment. Patients in the trial will be randomized to receive D2E7 or placebo and responses will be measured according to the Crohn’s Disease Activity Index (CDAI) score. The CDAI is a commonly used tool that measures factors such as weight loss and abdominal pain.
“Crohn’s disease is an immune disorder where patients experience sometimes severe gastrointestinal symptoms because of an inflammatory response in the intestinal tract,” said Stephen Hanauer, M.D., professor and director, Gastroenterology Section, Department of Medicine, University of Chicago. “Currently, patients with Crohn’s disease have limited treatment options to consider and this trial is designed to assess the effect of D2E7 in the treatment of these patients.”
Crohn’s disease is a serious inflammatory disease of the gastrointestinal (GI) tract, usually beginning in late childhood or early adulthood. Common symptoms include diarrhea, abdominal pain, weight loss, fever, and in some cases rectal bleeding.
D2E7 (adalimumab) is the first fully human monoclonal antibody to be developed. D2E7 works by specifically blocking the activity of tumor necrosis factor alpha (TNF-á), which plays a central role in the inflammatory responses of many autoimmune diseases. Regulatory submissions in the United States and Europe are based on data from 23 clinical trials in RA involving more than 2,300 patients in North America, Europe and Australia, making D2E7 the most-studied anti-TNF agent at the time of submission for regulatory approvals.
Monoclonal antibodies mimic naturally occurring antibodies and can recognize and neutralize proteins that play a role in promoting the inflammatory process associated with many autoimmune diseases. Fully human monoclonal antibodies have a protein structure that makes them essentially indistinguishable from antibodies present in the human body.