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

NCT05162131 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PB2452-PT-CL-0006
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Keywords

Ticagrelor; Platelet Aggregation Inhibitors; P2Y12 Receptor Antagonists

Outcome Measures

Primary Outcomes (11)

• Incidence and severity of AEs

  Time Frame: 60 days - Starting up to 28 days prior to dosing

• Incidence of Clinical Laboratory Abnormalities

  30 Day - Starting day of dosing

• Vital Sign Measurements - Changes in Diastolic Blood Pressure

  60 days - Starting up to 28 days prior to dosing

• Vital Sign Measurements - Changes in Systolic Blood Pressure

  60 days - Starting up to 28 days prior to dosing

• Vital Sign Measurements - Changes in Axillary Temperature

  60 days - Starting up to 28 days prior to dosing

• Vital Sign Measurements - Changes in Respiratory Rate

  60 days - Starting up to 28 days prior to dosing

• Vital Sign Measurements - Changes in Heart Rate

  60 days - Starting up to 28 days prior to dosing

• 12-Lead ECG - Incidence of clinically significant findings

  60 days - Starting up to 28 days prior to dosing

• Cardiac Telemetry Monitoring - Incidence of clinically significant findings

  3 Days - Starting day 1 day prior to dosing up to 2 days after dosing

• Physical examination - Incidence of clinically significant findings

  3 Days - Starting day 1 day prior to dosing up to 2 days after dosing

• Immunogenicity

  Incidence of Immunogenicity

  60 days

Secondary Outcomes (74)

• PB2452 Pharmacokinetic profile - (AUC) (Cohort 1-4)

  -10 minutes,0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours and 7 days

• PB2452 Pharmacokinetic profile - (AUC) (Cohort 5)

  -10 minutes,10 minutes, 30 minutes, 1, 2, 4, 8, 12, 16, 18, 20, 24, 28, 32, 36, 48, 72 hours and 7 days

• PB2452 Pharmacokinetic profile - (AUC0-t) (Cohort 1-4)

  -10 minutes,0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours and 7 days

• PB2452 Pharmacokinetic profile - (AUC0-t) (Cohort 5)

  -10 minutes,10 minutes, 30 minutes, 1, 2, 4, 8, 12, 16, 18, 20, 24, 28, 32, 36, 48, 72 hours and 7 days

• PB2452 Pharmacokinetic profile - Cmax (Cohorts 1-4)

  -10 minutes,0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours and 7 days

Study Arms (7)

1-a: 100 mg Bentracimab (PB2452) (no Placebo, no Ticagrelor)

EXPERIMENTAL

PB2452 Infusion

Drug: Bentracimab (PB2452) 100 mg or Placebo

1-b: 300 mg Bentracimab (PB2452) (no Placebo, no Ticagrelor)

EXPERIMENTAL

PB2452 Infusion

Drug: Bentracimab (PB2452) 300 mg or Placebo

1-c: 1000 mg Bentracimab (PB2452) or Placebo (no Ticagrelor)

EXPERIMENTAL

PB2452 Infusion or Placebo - Sodium Chloride

Drug: Bentracimab (PB2452) 1000 mg or Placebo

2: 1000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

EXPERIMENTAL

PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg + 90 mg bid for a total of 5 doses

Drug: Bentracimab (PB2452) 1000 mg or Placebo (With Ticagrelor Pre-Treatment)

3: 3000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

EXPERIMENTAL

PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg + 90 mg bid for a total of 5 doses

Drug: Bentracimab (PB2452) 3000 mg or Placebo (With Ticagrelor Pre-Treatment)

4: 9000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

EXPERIMENTAL

PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg + 90 mg bid for a total of 5 doses

Drug: Bentracimab (PB2452) 9000 mg or Placebo (With Ticagrelor Pre-Treatment)

5: 18000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

EXPERIMENTAL

PB2452 Infusion or Placebo - Sodium Chloride with Ticagrelor Oral Tablet: 180 mg + 90 mg bid for a total of 5 doses

Drug: Bentracimab (PB2452) 18000 mg or Placebo (With Ticagrelor Pre-Treatment)

Interventions

Bentracimab (PB2452) 100 mg or Placebo DRUG

Experiment 1-a: 100 mg Bentracimab (PB2452) (no Placebo, no Ticagrelor) Drug: PB2452 infusion 30 minute - 12-hour infusion

1-a: 100 mg Bentracimab (PB2452) (no Placebo, no Ticagrelor)

Bentracimab (PB2452) 300 mg or Placebo DRUG

Experiment 1-b: 300 mg Bentracimab (PB2452) (no Placebo, no Ticagrelor) Drug: PB2452 infusion 30 minute - 12-hour infusion

1-b: 300 mg Bentracimab (PB2452) (no Placebo, no Ticagrelor)

Bentracimab (PB2452) 1000 mg or Placebo DRUG

Experiment 1-c: 1000 mg Bentracimab (PB2452) or Placebo (no Ticagrelor) Drug: PB2452 Infusion 30 minute - 12-hour infusion Drug: Placebo - Sodium Chloride 30 minute - 12-hour infusion

1-c: 1000 mg Bentracimab (PB2452) or Placebo (no Ticagrelor)

Bentracimab (PB2452) 1000 mg or Placebo (With Ticagrelor Pre-Treatment) DRUG

Experiment 2: 1000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment) Drug: PB2452 infusion 30 minute - 12-hour infusion Drug: Placebo - Sodium Chloride 30 minute - 12-hour infusion Drug: Ticagrelor Oral Tablet - Pre-treatment Ticagrelor 180 mg + 90 mg bid for 5 doses prior to PB2452 or Placebo

2: 1000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

Bentracimab (PB2452) 3000 mg or Placebo (With Ticagrelor Pre-Treatment) DRUG

Experiment 3: 3000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment) Drug: PB2452 infusion 30 minute - 12-hour infusion Drug: Placebo - Sodium Chloride 30 minute - 12-hour infusion Drug: Ticagrelor Oral Tablet - Pre-treatment Ticagrelor 180 mg + 90 mg bid for 5 doses prior to PB2452 or Placebo

3: 3000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

Bentracimab (PB2452) 9000 mg or Placebo (With Ticagrelor Pre-Treatment) DRUG

Experiment 4: 9000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment) Drug: PB2452 infusion 30 minute - 12-hour infusion Drug: Placebo - Sodium Chloride 30 minute - 12-hour infusion Drug: Ticagrelor Oral Tablet - Pre-treatment Ticagrelor 180 mg + 90 mg bid for 5 doses prior to PB2452 or Placebo

4: 9000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

Bentracimab (PB2452) 18000 mg or Placebo (With Ticagrelor Pre-Treatment) DRUG

Experiment 5: 18000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment) Drug: PB2452 infusion 30 minute - 12-hour infusion Drug: Placebo - Sodium Chloride 30 minute - 12-hour infusion Drug: Ticagrelor Oral Tablet - Pre-treatment Ticagrelor 180 mg + 90 mg bid for 5 doses prior to PB2452 or Placebo

5: 18000 mg Bentracimab (PB2452) or Placebo (Ticagrelor Pre-treatment)

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• SFJ Pharmaceuticals, Inc.: lead

Study Sites (1)

Beijing Friendship Hospital

Tongzhou, Beijing Municipality, China

Location

MeSH Terms

Interventions

PB-2452

Study Officials

• Dong Ruihua

  Beijing Friendship Hospital, 101 Luyuan Est. Rd., Tongzhou District, Beijing, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: December 17, 2021
• Study Start: December 25, 2021
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: January 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)