CSL Behring today announced that the first patient has been enrolled in the pivotal pediatric phase III study to evaluate the efficacy, safety and pharmacokinetics of its novel investigational recombinant factor VIII single chain (rVIII-SingleChain) for the treatment of previously treated children (up to age 11 years) with severe hemophilia A. The study site for this first enrollment is Malaysia.
A minimum of 25 previously treated subjects from six to 11 years of age and at least 25 subjects under six years of age who have undergone more than 50 exposure days with a previous factor VIII product are planned to be enrolled in this international, multicenter, open-label study. Subjects will be assigned to either an on-demand or prophylaxis treatment regimen for the treatment of bleeding episodes and will receive rVIII-SingleChain at a dose to be determined by the investigator. Hemostatic efficacy will be assessed by the subject or caregiver and the investigator, who will assess overall efficacy by a 4-point scale.
In an earlier study, rVIII-SingleChain showed improved pharmacokinetics over octocog alfa, the comparator, and demonstrated a safety and efficacy profile that supported advancement to late-stage clinical development. CSL Behring, in collaboration with its parent company CSL Limited, is developing rVIII-SingleChain for the treatment of hemophilia A as part of the AFFINITY clinical trial program.
Recombinant FVIII molecules currently available consist of a heavy and a light chain. Under certain conditions, these chains can dissociate, resulting in the formation of separated, or "dissociated," rFVIII chains that are not hemostatically active. The CSL Behring rVIII-SingleChain uses a strong, covalent bond that connects the light and heavy chains, thereby creating a stable single chain rFVIII.
In-house CSL Behring studies have shown that the molecular integrity of rVIII-SingleChain is significantly increased using the single-chain design, resulting in a homogenous product that is more stable than currently available FVIII products. In addition, in-vitro studies have shown that rVIII-SingleChain demonstrates a strong affinity for von Willebrand factor (VWF), resulting in a faster and more efficient binding to VWF. The FVIII/VWF complex plays an important role in the physiological activity and clearance of FVIII and has been shown to have an influence on the presentation of FVIII to the immune system.
Hemophilia is a congenital bleeding disorder characterized by prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs. In nearly all cases, it affects only males. The disease is caused by deficient or defective blood coagulation proteins known as factor VIII or IX. The most common form of the disease is hemophilia A, or classic hemophilia, in which the clotting factor VIII is either deficient or defective. Hemophilia B is characterized by deficient or defective factor IX. Hemophilia A affects approximately 1 in 5,000 to 10,000 people. Hemophilia B affects approximately 1 in 25,000 to 50,000 people. The recommended treatment for people with hemophilia deficiency is to treat by replacement factor therapy.
About CSL Behring
CSL Behring is a leader in the plasma protein therapeutics industry. Committed to saving lives and improving the quality of life for people with rare and serious diseases, the company manufactures and markets a range of plasma-derived and recombinant therapies worldwide.
CSL Behring therapies are used around the world to treat coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies, hereditary angioedema and inherited respiratory disease, and neurological disorders in certain markets. The company’s products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in the newborn. CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL Limited, a biopharmaceutical with headquarters in Melbourne, Australia. For more information, visit www.cslbehring.com.
Sheila A. Burke
Director, Communications & Public Relations
Worldwide Commercial Operations
Sheila.Burke at cslbehring.com