ATLANTA (March 18, 2021) – Researchers at Children’s Healthcare of Atlanta developed a new method for treating patients with severe hemophilia A in 2019. “The Atlanta Protocol” involved combining an old approach, immune tolerance induction (ITI), with the drug, emicizumab. The treatment was effective in four out of seven patients who were able to rid their bodies of the disease’s stubborn antibody inhibitors.
Given the successful results, Robert Sidonio, MD, a Pediatric Hematologist and Oncologist with the Aflac Cancer and Blood Disorders Center of Children’s, is further investigating the approach in a larger group of patients as co-principal investigator of an international, multi-site trial with Carmen Escuriola-Ettingshausen, MD, Director of the Hämophilie-Zentrum Rhein Main in Mörfelden-Walldorf, Germany. With Dr. Sidonio leading for North America, and Dr. Escuriola-Ettingshausen for Europe, they will help determine the safety and effectiveness of the Atlanta Protocol in a larger group of patients with severe Hemophilia A during a study called MOTIVATE, or MOdern Treatment of Inhibitor-positiVe pATiEnts with hemophilia A.
“The goal of MOTIVATE is to document established and current ITI approaches focusing on the newly-developed Atlanta Protocol,” said Dr. Sidonio. “The study will also analyze the impact of different treatment approaches in the prevention of bleeding in hemophilia A patients who develop inhibitors.”
Hemophilia A, also known as factor VIII deficiency, is an inherited bleeding disorder that causes abnormal blood clotting, resulting in more bleeding than normal due to low levels of factor VIII, a protein needed to form blood clots. Nearly 1 in 5,000 males and about 20,000 people in the United States have hemophilia A and B. About one-third of severe hemophilia A patients will develop even worse bleeding due to inhibitors, antibodies generated by the patient’s body against their treatment.
The inhibitors or antibodies against factor VIII limit physicians’ ability to stop bleeds with the standard intravenous factor replacement therapy, factor VIII concentrates. Although successful in about 70% of patients, traditional ITI requires daily infusions through a vein at a high dose. Usually a temporary line must be implanted, as ITI may take at least two years to be effective.
Emicizumab, U.S. Food and Drug Administration (FDA)-approved for hemophilia A patients with and without inhibitors, is given under the skin and less frequently to control bleeding. When combining emicizumab and the standard ITI approach during "The Atlanta Protocol," most patients were able to rid their bodies of inhibitors. MOTIVATE will expand on this single center study and characterize 120 participants with inhibitors. Patients will be divided into three groups: those receiving ITI alone with FVIII, those receiving ITI with emicizumab ("The Atlanta Protocol") and those receiving emicizumab alone. They will be followed for up to five years.
“We hope MOTIVATE is equally successful to 'The Atlanta Protocol,' only on larger scale with greater implications for expanded use,” said Dr. Sidonio.
"The Atlanta Protocol" was developed by three pediatric hematologists and oncologists at Children’s, including Dr. Sidonio, Glaivy Batsuli, MD, and Shannon Meeks, MD. Dr. Sidonio is also an associate professor at the Emory University School of Medicine Department of Pediatrics and Director of Clinical Research for the Hemostasis and Thrombosis Program at Children's. MOTIVATE is registered as a non-interventional study in the U.S. (NCT04023019) and as a low-interventional, pragmatic trial in Europe (EudraCT No. 2019-003427-38). The MOTIVATE trial includes sites in the US, Canada and European Union, and is supported by funding from Octapharma AG in Lachen, Switzerland. To learn more, visit clinicaltrials.gov/ct2/show/NCT04023019.