Study to Evaluate the Safety, Tolerability, PK, and PD of PB2452 With and Without Ticagrelor Pretreatment in Chinese Healthy Volunteers

  • STATUS
    Recruiting
  • End date
    Nov 30, 2022
  • participants needed
    40
  • sponsor
    PhaseBio Pharmaceuticals Inc.
Updated on 24 March 2022
Accepts healthy volunteers

Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose, sequential group study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PB2452 (Bentracimab) with and without ticagrelor pretreatment when administered to Chinese healthy male and female subjects.

Up to 6 dose levels will be evaluated. This study will have 5 cohorts and a total of 40 subjects with 8 healthy subjects per cohort. Cohort 1 will be split into 3 parts, Cohort 1-a, 1-b and 1-c. The starting dose of PB2452 will be 100 mg and the planned doses for subsequent parts or cohorts are 300, 1000, 3000, 9000, and 18000 mg.

Description

The study will consist of a screening period (Days -28 to -4), check-in/pretreatment (Day -3 to -1), an in-house treatment period (Days 1 through 4), and follow-up visits (Days 7 and 28 (+2 days)). Subjects will receive an IV dose of study drug on Day 1.

On Day 1, subjects who meet all of the inclusion criteria and none of the exclusion criteria will be assigned to treatment before dosing. For Cohorts 1-c and 2 to 5, subjects will be randomly assigned to receive PB2452 or placebo in a ratio of 3:1.

Details
Condition Healthy
Treatment Bentracimab (PB2452) 100 mg or Placebo, Bentracimab (PB2452) 300 mg or Placebo, Bentracimab (PB2452) 1000 mg or Placebo, Bentracimab (PB2452) 1000 mg or Placebo (With Ticagrelor Pre-Treatment), Bentracimab (PB2452) 3000 mg or Placebo (With Ticagrelor Pre-Treatment), Bentracimab (PB2452) 9000 mg or Placebo (With Ticagrelor Pre-Treatment), Bentracimab (PB2452) 18000 mg or Placebo (With Ticagrelor Pre-Treatment)
Clinical Study IdentifierNCT05162131
SponsorPhaseBio Pharmaceuticals Inc.
Last Modified on24 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

The subject is born in China to parents and grandparents of Chinese descent. Have not resided more than 5 years outside of China at the time of consent
The subject is male or female 20 ≤ age ≤ 64
The subject has a body mass index 18 ≤ BMI ≤35 kg/m2 and a weight of ≥45 kg but ≤120 kg, inclusive, at screening
The subject is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings at screening
Specific inclusionary laboratory values at screening and check-in require the
following
Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), total serum bilirubin and alkaline phosphatase levels without clinically significant abnormality per investigator's discretion
White blood cell (WBC) count, platelet count, hemoglobin level without clinically significant abnormality per investigator's discretion
Thyroid stimulating hormone (TSH) level without clinically significant abnormality per investigator's discretion at screening
Prothrombin time (PT) and partial thromboplastin time (PTT) level without clinically significant abnormality per investigator's discretion
Female subjects of childbearing potential must not be pregnant, lactating, or planning
to become pregnant before 3 months after the last dose of study drug, and have
a negative serum pregnancy test at screening and check-in. Female subjects of
childbearing potential must use 2 effective methods of birth control (hormonal
contraceptives [i.e., oral, implantable, patch, or injectable contraceptives
hormone-containing intrauterine device that has been in place for at least 2
months prior to screening] in combination with a barrier method [i.e
condoms, sponge, diaphragm, or cervical cap with spermicidal gels or cream])
from 30 days before study drug administration through the end of the study
Double barrier method of condom and spermicide without hormonal
contraceptives, or confirmation of sexual abstinence is acceptable, as well as
vasectomy for male subjects or male partners of female subjects. Women are
considered not to be of childbearing potential if they have fulfilled one of
the following criteria: documentation of irreversible surgical sterilization
(i.e., hysterectomy, or bilateral oophorectomy [not tubal ligation]), or
postmenopausal (defined as amenorrhea for 12 consecutive months following
cessation of all exogenous hormonal treatments, and documented plasma
follicle-stimulating hormone level >40 IU/mL, or amenorrhea for 24 consecutive
months). Male subjects with partners of childbearing potential must agree to
use appropriate and effective measures of contraception (e.g., condom plus
diaphragm with spermicide; condom plus spermicide) during the study and for 30
days after the last dose of study drug, and to refrain from donating sperm for
at least 7 days prior to the dose of study drug and until at least 90 days
following the last dose of study drug
The subject agrees to comply with all protocol requirements
The subject is able to provide written informed consent

Exclusion Criteria

History of any clinically significant acute or chronic disease or medical disorder
History or presence of gastrointestinal, hepatic (with the exception of Gilbert's syndrome), or renal disease or renal insufficiency (i.e., estimated glomerular filtration rate <60 ml/min/1.73m2), or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
Specific exclusionary criteria for ECG parameters at screening or check-in are any of the following
Prolonged Fridericia-corrected QT interval (QTcF) >450 milliseconds (msec), shortened QTcF <340 msec, or pause >3 seconds, or family history of long QT syndrome
Prolonged PR (PQ) interval >240 msec, intermittent second- or third-degree atrioventricular (AV) block or AV dissociation, or shortened PR interval <120 msec
Incomplete, full, or intermittent bundle branch block (QRS <110 msec with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy
Any increased risk of bleeding, including the following
Recent history (within 30 days preceding the first dose of study drug) of gastrointestinal bleeding
Any history of severe head trauma, intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy
Any history of intracranial, intraocular, retroperitoneal, or spinal bleeding
Any recent (within 30 days preceding the first dose of study drug) major trauma
History of hemorrhagic disorders that may increase the risk of bleeding (e.g., hemophilia, von Willebrand's disease)
Receiving chronic treatment with nonsteroidal anti-inflammatory drugs (including aspirin [greater than 100 mg daily]), anticoagulants, or other antiplatelet agents that cannot be discontinued (including clopidogrel, prasugrel, ticlopidine, dipyridamole, or cilostazol)
Have taken, within 30 days of screening, any anticoagulants including low molecular-weight heparin, or other antiplatelet agents
Have taken non-steroidal anti-inflammatory medications, including aspirin within 14 days of screening
The subject has a positive test result for hepatitis B surface antigen, hepatitis C
virus antibody, or human immunodeficiency virus types 1 or 2 antibodies at
screening
Concomitant oral or IV therapy with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers, which cannot be stopped within at least 5 half-lives, but not shorter than 10 days, before randomization
Any prescription or over-the-counter medications (except paracetamol [up to 2 g per day] or as indicated per protocol e.g. for birth control), including herbal or nutritional supplements, within 14 days before the first dose of study drug
The subject has consumed grapefruit or grapefruit juice, Seville orange or Seville orange-containing products (e.g., marmalade), or alcohol-, or xanthine-containing products within 48 hours before dosing with study drug
The subject is participating in any other study within 30 days of the administration of study drug in this study
The subject is taking part in a non-medication study which, in the opinion of the investigator, would interfere with the outcome of the study
The subject has received another new chemical entity (defined as a compound which has not been approved for marketing) or any marketed or investigational biologic agent within 30 days of the administration of study drug in this study or 5 half-lives of the experimental medication, whichever is longer
The subject has involvement with any sponsor or study site employee or their close relatives (e.g., spouse, parents, siblings, or children whether biological or legally adopted)
The subject has previously received PB2452 or had been randomized to receive study drug in an earlier cohort for this study
The subject is a smoker or has used nicotine or nicotine-containing products (e.g., snuff, nicotine patch, nicotine chewing gum, e- cigarettes, mock cigarettes, or inhalers) within 3 months before the infusion of study drug
The subject has a known or suspected history of alcohol/drug abuse or has a positive test result for drugs of abuse, alcohol, or cotinine at screening or check-in
The subject has been involved in strenuous activity or contact sports within 48 hours before the admission and while confined in the clinical site
The subject has donated blood or plasma within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to the infusion of study drug
The subject has a history of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to ticagrelor, any biologic therapeutic agent, or any significant food allergy that could preclude a standard diet in the clinical site
Concern for the inability of the subject to comply with study procedures and/or follow-up, or, in the opinion of the investigator, the subject is not suitable for entry into the study
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