Trial of Andexanet Alfa in ICrH Patients Receiving an Oral FXa Inhibitor

Inclusion Criteria

• •1. Written informed consent. Either the patient or his or her medical proxy (or legally authorized representative if permissible by local or regional laws and regulations) has been adequately informed of the nature and risks of the study and has given written informed consent prior to Screening.
• •* Deferred consent procedure is allowed where approved by local ethics committees. In cases of deferred consent, the time of the study physician's documented decision to include the patient into the study will serve as "time of consent" with respect to protocol-specific procedures.
• •* In all cases where the patient does not sign informed consent prior to study entry, informed consent from the patient will be obtained as soon as realistically possible after inclusion in the trial and in accordance with the Declaration of Helsinki, International Conference on Harmonization-Good Clinical Practice (GCP), the EU General Data Protection Regulation (GDPR) and national and local regulations.
• •2. Age ≥ 18 years old at the time of consent.
• •3. An acute intracerebral bleeding episode, defined as an estimated blood volume ≥ 0.5 to ≤ 60 mL acutely observed radiographically within the cerebrum. Patients may have extracerebral (e.g., subdural, subarachnoid, epidural) or extracranial (e.g., gastrointestinal, intraspinal) bleeding additionally, but the intracerebral hemorrhage must be considered the most clinically significant bleed at the time of enrollment.
• •4. Performance of a head CT or MRI scan demonstrating the intracerebral bleeding within 2 hours prior to randomization (the baseline scan may be repeated only once to meet this criterion).
• •5. Treatment with an oral FXa inhibitor (apixaban \[last dose 2.5 mg or greater\], rivaroxaban \[last dose 10 mg or greater\], or edoxaban \[last dose 30 mg or greater\]):
• •* ≤ 15 hours prior to randomization.
• •* \> 15 hours prior to randomization or unknown time of last dose, if documented anti fXa activity is \> 100 ng/mL for direct fXa inhibitors (apixaban, rivaroxaban or edoxaban) may be enrolled, irrespective of the time of the last dose, and the local anti-fXa activity level is obtained within 2 hours prior to consent, performed as per standard of care. Note: Patients enrolled in this manner should receive a high andexanet dosing regimen.
• •6. Time from bleeding symptom onset \< 6 hours prior to the baseline imaging scan. Time of trauma (if applicable) or time last seen normal may be used as surrogates for time of symptom onset. (If the baseline scan is repeated to meet Inclusion Criterion #4, the time from bleeding symptom onset must be \< 6 hours prior to the repeat baseline imaging scan.)
• •7. Female patients of childbearing potential and male patients with female partners of childbearing potential must follow protocol-specified guidance for avoiding pregnancy for 30 days after the last dose of study drug.
• •8. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
• •9. NIHSS score ≤ 35 at the time of consent.