The three Explorer studies — the Phase 2 Explorer 5 (NCT03196297), and the global Phase 3 Explorer 7 (NCT04083781) and Explorer 8 (NCT04082429) — are all investigating the safety and efficacy of concizumab as a prophylatic (preventive) treatment for bleeding episodes in patients with hemophilia A and B, with and without inhibitors.
The company’s decision was based on thrombotic events (obstructed blood flow due to blood clots), all not fatal, in three patients participating in the late-stage Phase 3 program.
Until further notice, no new patients will be recruited into any of the trials, and treatment is stopping for the approximately 109 people already enrolled and receiving concizumab.
“While it is disappointing to pause the trials, patient safety is of utmost importance to Novo Nordisk — both for those taking part in our clinical trials and those who use our products on a daily basis” Mads Krogsgaard Thomsen, Novo Nordisk’s executive vice president and chief science officer, said in a press release.
“Together with relevant authorities, we will now carefully evaluate all available data and decide how to best move forward,” Thomsen added.
Novo Nordisk and an independent data monitoring committee are studying these events, considered serious, and their relevance to the trials. No conclusions have been reached to date, the company said.
Concizumab is an antibody designed to target a natural anticoagulant protein called tissue factor pathway inhibitor (TFPI). By blocking TFPI, concizumab promotes the production of thrombin, a blood clotting protein, potentially improving blood coagulation and preventing spontaneous bleeds.
The therapy is self-administered directly under the skin using a pen-injector; this can be done at home.
Six-month data from two Phase 2 trials, Explorer 4 (NCT03196284) and Explorer 5, showed that concizumab, given once-a-day, safely and effectively lowered the bleeding rates of patients with hemophilia A or B with inhibitors, and hemophilia A without inhibitors.
No severe adverse events, adverse event-related withdrawals, or thromboembolic events (when a blood clot breaks loose and travels through the bloodstream to plug another vessel) were reported.
These Phase 2 studies, which involved a total of 53 patients recruited at more than 10 countries, worked as proof-of-concept trials and supported the initiation of the Phase 3 clinical program.
Explorer 7 and 8 are evaluating the safety and efficacy of once-daily prophylactic treatment with concizumab in hemophilia A and B patients with inhibitors (Explorer 7) and without them (Explorer 8) for up to three years.
They were expected to recruit up to 293 patients across 32 countries.
People usually treated on an on-demand basis were being randomly assigned to either concizumab, or to continue their normal treatment regimen for six months, after which they would start using concizumab. Those usually on prophylatic treatment or who had been given concizumab in a previous Phase 2 trial were assigned to concizumab treatment.
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