• What is DEFEND-2?
• Where are the study sites?
• Who can participate?
• What's expected?
• Why do it?
• What else should I know?
• Where can I go for more information?

What is DEFEND-2?

DEFEND-2 is a phase 3 clinical study evaluating the use of otelixizumab in people with newly diagnosed type 1 diabetes. Otelixizumab is an investigational agent, which means it has not been approved by the FDA for marketing. The goal of DEFEND-2 is to find out whether otelixizumab can help people with type 1 diabetes by preserving their ability to make their own insulin.

DEFEND-2 is being conducted in North America and Europe for eligible participants 12 to 45 years old. It is a placebo-controlled study, which means that some participants will receive otelixizumab and some will receive placebo (an inactive substance that does not contain any otelixizumab). Participants will randomly receive either otelixizumab or placebo. Two-thirds of the participants will receive otelixizumab and one-third will receive placebo.

The study is "masked" or "blinded," which means that neither you nor your physician nor the sponsor will know whether you are receiving otelixizumab or placebo. The otelixizumab or placebo will be given intravenously (IV) every day for 8 consecutive days. You will spend most of the day at the study center for these 8 days, but there are no planned overnight stays. There will be periodic follow-up visits for a total of 2 years after you receive otelixizumab or placebo. At the end of the 24-month study, you and your physician will find out whether you received otelixizumab or placebo.

• What is a phase 3 study?

  A phase 3 study is an experimental study in which an investigational agent is given to a relatively large number of people to assess its effectiveness. Information on side effects and safety is also collected. A phase 3 study typically follows phase 1 and phase 2 studies that observe smaller numbers of people where dose regimens and schedules are refined, side effects are intensively studied, and early indication of benefits may be found. For more information about clinical trials, visit www.ClinicalTrials.gov

• What is the investigational agent being studied?

  Otelixizumab is a monoclonal antibody that is being developed and tested for the treatment of type 1 diabetes and other autoimmune diseases. Otelixizumab is an anti-CD3 antibody, which means that it binds to a group of molecules called CD3. CD3 is found on all T cells (a type of white blood cell called lymphocytes — an important part of the body's immune system).

  In type 1 diabetes, some T cells (called T effector cells) mistakenly attack and destroy the cells in the pancreas that make insulin — the beta cells. Otelixizumab is being studied to determine if it can reduce this attack on beta cells, preserving the beta cells’ normal ability to make insulin.

  Current treatments for type 1 diabetes consist of diet, exercise, and the administration of insulin. However, these treatments do not affect the underlying cause of the disease.

  

  The way otelixizumab may work is unknown; however, the best theory at the present time is that otelixizumab appears to stop the immune system from destroying beta cells in at least 2 distinct ways:

  • First, by stopping T effector cells (which can harm and destroy beta cells)
  • Second, by activating a type of T cell called a T regulatory cell, which protects the beta cells from further attack by T effector cells

• What is type 1 diabetes? What are the limitations of current treatment options?

  According to the Centers for Disease Control and Prevention (CDC), as of 2005, 20.8 million people in the U.S. have diabetes, of which 5% to 10% have type 1 diabetes. In the U.S., 36,000 new patients are diagnosed with type 1 diabetes each year.

  Type 1 diabetes is an autoimmune disease in which the body's immune system attacks and destroys the insulin-producing cells (the beta cells) of the pancreas. Current treatments for type 1 diabetes consist of managing blood glucose levels through diet, exercise, and injections of insulin. Insulin injections attempt to replace the natural insulin produced by the beta cells in the pancreas. This approach does not affect the underlying cause of the disease — the autoimmune attack on the beta cells.

  Visit the Resource Center for more information about type 1 diabetes.

• Who is sponsoring the study?

  DEFEND-2 is being sponsored by Tolerx, Inc. Tolerx is a biopharmaceutical company engaged in discovering and developing therapies for autoimmune diseases, including type 1 diabetes. For more information about Tolerx, visit www.tolerx.com.