The trials were paused in March due to the occurrence of non-fatal thrombotic (blood-clotting) events in three patients.
In collaboration with relevant authorities, Novo Nordisk established new safety measures and guidelines based on its analysis of all available data. The U.S. Food and Drug Administration has agreed on these changes and lifted the clinical hold.
“I am pleased that we are able to safely restart the Explorer trials. This emphasizes Novo Nordisk’s long-term dedication to the hemophilia community and our commitment to develop new subcutaneous prophylaxis options for all hemophilia patients,” Mads Krogsgaard Thomsen, DVM, PhD, executive vice president and chief scientific officer of Novo Nordisk, said in the release.
The three Phase 3 trials — Explorer, 6, 7, and 8 — will resume as soon as local procedures allow.
Explorer 7 is investigating the use of concizumab in patients with hemophilia A or B with inhibitors toward FVIII or FIX. The trial intends to establish the safety and effectiveness of once-daily prophylactic subcutaneous concizumab in reducing the number of bleeds over three years.
Participants are assigned randomly to one of two groups. In the first group, patients will receive concizumab from the start of the study; the second group will continue with its normal medicine and start concizumab after six months. They will administer the medication at home themselves, using a pen injector.
Parallel to that trial, Explorer 8 is investigating concizumab in patients with hemophilia A or B without inhibitors. The trial’s design is similar to Explorer 7.
Explorer 6 (NCT03741881) does not specifically investigate concizumab, but rather is an observational study of bleeding and quality of life in people with severe congenital hemophilia A and B, with or without inhibitors. Data from this study is used to make comparisons between patients.
In this study, participants are tracked over the course of about two-and-a-half years, during which they will keep a diary noting the number and treatment of their bleeds. They also wear a tracker on their wrist to monitor their activity levels for up to 12 weeks.
The Phase 2 Explorer 5 study (NCT03196297) also had been paused, but now has been completed. Patients who were participating in that trial at the time of treatment pause will be offered screening in Explorer 8, a company spokesperson said in an email.
Concizumab is an antibody that targets a natural anticoagulant protein called tissue factor pathway inhibitor. By blocking the anticoagulant, concizumab facilitates the production of thrombin, a blood-clotting protein. This may prevent spontaneous bleeds by improving blood coagulation.
The trials are enrolling a total of approximately 293 patients from 32 countries. According to the company spokesperson, it will take some time to update the status on the trial webpages, which currently show the studies are suspended, but more information concerning enrollment can be found on the company’s website.
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