ATN-106 clinical study
"I'm driven by curiosity, and that has a high value for me. If you lose it, you've lost interest and focus, which are both essential."
Senior Clinical Project Manager for Haematology
When Octapharma launched the ATN-106 clinical study in 2021, it made perfect sense to turn to Martina Jansen, Senior Clinical Project Manager for Haematology, to lead this critical project even though much of her expertise lay in a completely unrelated field.
ATN-106 aims to establish the safety and efficacy of Octapharma’s human antithrombin concentrate, for the treatment of patients with congenital antithrombin deficiency. The study faces enormous challenges, not least in finding patients to participate. With more than 26 years at Octapharma and many successful projects under her belt, however, Martina is confident that she and her team will bring it to a successful conclusion.
Antithrombin is a protein in the blood that prevents abnormal blood clots from forming. It helps the body maintain a healthy balance between bleeding and clotting.
Congenital antithrombin deficiency is a rare inherited disease that is commonly associated with unprovoked thrombotic events (TEs) and thromboembolic events (TEEs). These can present significant risks during surgical procedures and childbirth which can be effectively managed through antithrombin replacement therapy, such as that offered by intravenous infusion of atenativ®.
Octapharma initiated a study of its human antithrombin concentrate for use in patients with congenital antithrombin deficiency undergoing a surgical procedure or parturition (childbirth). “Octapharma’s human antithrombin concentrate has a long heritage of indispensable use in critical clinical settings since 1982,” Oliver Hegener, VP Head of IBU Critical Care, explains. “The product is available for treatment in 30 countries worldwide, but it is currently not registered in the USA. With the ATN-106 study results, Octapharma will seek market authorisation to make this product available to physicians in the USA.”
What is congenital antithrombin deficiency?
Hereditary antithrombin deficiency is a disorder of blood clotting. People with this condition have a higher than average risk off developing abnormal blood clots.
It is estimated that
0.03—0.05% of people have hereditary antithrombin deficiency.
Of people who have experienced an abnormal bloodcot 0.5—5% have hereditary antithrombin deficiency.
In November 2021, negotiations with the US Food and Drug Administration (FDA) were finalised and Octapharma received the green light to proceed with ATN-106. Earlier in 2021, the study team had begun selecting vendors, including an operational contract research organisation (CRO) to manage submissions to ethics committees and health authorities, a data management supplier and a central laboratory.
“The first patient was enrolled in the study at The Bleeding & Clotting Disorders Institute (BCDI), Peoria, Illinois, under Principal Investigator Dr Michael Tarantino, MD, on September 12, 2022,” says Martina. “We have already identified a second patient, also from the USA. Most of the European study sites involved are now activated, which means they are ready to enrol as soon as patients are identified.”
The primary objective of the ATN-106 study is to assess the incidence of TEs and TEEs in 20 patients with congenital antithrombin deficiency under cover of Octapharma’s human antithrombin concentrate for surgical procedures or parturition. In addition, a minimum of 14 adult patients between 18 and 80 years of age with congenital antithrombin deficiency who are not pregnant will be enrolled in a pharmacokinetic phase of the study. A further four patients between 12 and 16 years of age will also be enrolled in this phase in the USA. Ultimately, patients will be enrolled in seven European countries in addition to the USA.
“The biggest challenge facing ATN-106 is that congenital antithrombin deficiency is a rare disease that presents issues rarely. There are very few patients, with very few specialists, and the only established product on the market in the USA was authorised more than 30 years ago,” says Wolfgang Frenzel, Board Member for R&D.
“Fortunately, Octapharma has consistently invested in people, providing a safe and stable environment in which they can flourish. As a result, we’re now in the happy position to have people who are ready and eager to resolve the challenges the congenital antithrombin deficiency community are currently facing.”
“We have two and a half years to enrol 40 patients,” says Martina. “I’m confident that we can achieve this goal by the end of 2024 but, of course, we already have a strategy in place to collaborate with further study sites if needed.”
Hereditary antithrombin deficiency is caused by mutations in the SERPINC1 gene. This gene provides instructions for producing a protein called antithrombin. Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin.
Most of the mutations that cause hereditary antithrombin deficiency change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional antithrombin to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots.
Carrying out a clinical trial in such a rare disease requires a huge amount of patience and an awareness of the entire project. “I’m driven by curiosity,” says Martina, “and that has a high value for me. If you lose it, you’ve lost interest and focus, which are both essential.”
She relishes the spirit at Octapharma. “There’s a curiosity to be creative here, to be flexible, that leads teams at Octapharma to grow and to constantly challenge themselves,” she says.
That curiosity and drive is motivating much of the continuing study of Octapharma’s human antithrombin concentrate. “This product has a huge potential beyond congenital deficiency and further possible clinical programmes are already under discussion,” adds Martina. “That is very exciting.”