Bentracimab (PB2452) in Ticagrelor-treated Patients With Uncontrolled Major or Life-Threatening Bleeding or Requiring Urgent Surgery or Invasive Procedure

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center, open-label, prospective single-arm study of reversal of the antiplatelet effects of ticagrelor with bentracimab (PB2452) in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedure.

Approximately 200 patients will be enrolled from approximately 200 centers in North America, Europe, and Asia-Pacific regions, including mainland China. Patients with reported use of ticagrelor within the prior 3 days who require urgent ticagrelor reversal will be eligible for enrollment. These populations will be enrolled based on separate inclusion criteria.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PhaseBio Pharmaceuticals Inc.
• Treatments: Ticagrelor

Criteria

Inclusion Criteria:

• Patients will be eligible for inclusion into the study if they meet all of the following criteria:

1. Male or female >18 years of age with documented or verbal informed consent

2. History or documentation of ticagrelor intake within the prior 3 days

3. Patients described below who require urgent reversal of the antiplatelet effects of ticagrelor:

Patients with uncontrolled major or life-threatening bleeding, requiring urgent reversal of the antiplatelet effects of ticagrelor. It is expected that enrolled patients would have characteristics similar to those described below:

• Potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise, e.g., systolic blood pressure < 90 mm Hg and signs or symptoms of low cardiac output not otherwise explained

• Bleeding in a critical organ or closed space, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular bleed with compartment syndrome

• Visible, uncontrolled bleeding associated with a corrected hemoglobin level < 8.0 g/dL, a fall in hemoglobin level of ≥ 2.0 g/dL (1.24 mmol/L) from a known baseline, or requirement for transfusion of 2 or more units of packed red blood cells (PRBC)

Patients requiring urgent surgery or invasive procedure when it is not medically advisable either to proceed urgently with impaired hemostasis or to delay the urgent procedure for 3 or more days as directed by ticagrelor labeling due to the high risk of bleeding. These patients may typically be in any of the following clinical situations:

• Requires urgent surgery or invasive procedure known to be associated with a risk of significant bleeding (such as cardiac surgery, neurosurgery, or major orthopedic surgery)

• Requires urgent surgery or invasive procedure that may have an adverse procedural outcome if hemostasis is impaired (such as neurological, spinal, ophthalmological, urological, or orthopedic surgery)

• At risk of experiencing life-threatening events, such as, shock, myocardial infarction, or stroke, if significant intraoperative or postoperative bleeding occurs (such as in elderly patients or patients with underlying cardiac or pulmonary disease who have limited cardiopulmonary reserve)

Exclusion Criteria:

1. Known sensitivity or contraindication to PB2452 or any of its excipients

2. Patients in whom ticagrelor reversal is not considered urgent, e.g., patients with stable or non-acute conditions who have low hemoglobin due to chronic, low-grade gastrointestinal bleeding or who have stable, remote, or asymptomatic intracranial hemorrhage

3. Patients expected to be clinically unsalvageable, such as, patients with intracranial hemorrhage with Glasgow Coma Scale ≤ 8, or an intracerebral hematoma volume > 60 cc or patients with overwhelming sepsis

4. Any condition which, in the opinion of the investigator, would make it unsafe or unsuitable for the patients to participate in this study. This includes assessment of likelihood to cooperate with study follow-up visits and procedures

• Known pregnancy may be exclusionary in some regions or countries as directed by national health authorities and/or local IRBs/Ethics Committees

5. Known use of clopidogrel, prasugrel or ticlopidine within 5 days of study drug administration; known use of antiplatelet GPIIb/IIIa inhibitors, or cangrelor within 5 half-lives of expected study drug administration; or known use of warfarin, rivaroxaban, apixaban, or edoxaban within 5 half-lives or expected study drug administration

6. Known recent use (< 5 day) of vitamin K, prothrombin complex concentrate, recombinant factor VIIa, whole blood or plasma transfusions, idarucizumab, or andexanet-alfa (coagulation factor Xa (recombinant), inactivated-zhzo)