A Study of PB2452 in Patients with Uncontrolled Major or Life-Threatening Bleeding or Requiring Urgent Surgery or Invasive Procedure

Phase 1

• Conditions: ncontrolled Major or Life Threatening Bleeding or Requiring Urgent Surgery or Invasive Procedure; MedDRA version: 21.1Level: LLTClassification code 10053756Term: Invasive procedureSystem Organ Class: 100000004865; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2019-004457-92-DE
• Lead Sponsor: SFJ Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-12-09
• Last Update Posted: 9 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Male or female > 18 years of age with documented or verbal informed consent. Emergency consent may be obtained where permitted by local regulations and institutional approval
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 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)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

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 end-stage cancer 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 study drug administration;
or known use of warfarin, dabigatran, rivaroxaban, apixaban, or
edoxaban within 5 half-lives of expected study drug administration
6. Known recent use (< 5 day) of vitamin K, prothrombin complex
concentrate, recombinant factor VIIa, idarucizumab, or andexanet-alfa (coagulation factor Xa
(recombinant), inactivated-zhzo)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified