Study to Evaluate the Safety, Tolerability, PK and PD of PB2452 in Healthy Younger, Older and Elderly Subjects

NCT03928353 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PB2452-PT-CL-0002
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2A, randomized, double-blind, placebo-controlled, single dose, sequential group study to evaluate the safety, tolerability, PK, and PD of PB2452 vs matching placebo with ticagrelor (with or without acetylsalicylic acid (ASA)) pretreatment when various dose levels and administration regimens are administered to healthy younger (ages 18 to 50), older (ages 50 to 64 years) and elderly (ages 65 to 80 years) male and female subjects. Up to 5 dose levels and/or administration regimens will be evaluated in up to 5 cohorts. Each cohort will include approximately 8 to 12 subjects randomized in a 3:1 ratio (PB2452:placebo).

Conditions

Healthy

Outcome Measures

Primary Outcomes (15)

• Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs)

  An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug-related. A TEAE is defined as any AE not present before exposure to study drug or any AE already present that worsens in intensity or frequency after exposure to study drug. An SAE/suspected unexpected serious adverse reaction if, in the view of either the investigator or Sponsor, it results in any of the following outcomes: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or congenital anomaly or birth defect. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

  Day -3 up to Day 28

• Number of Participants With Clinical Laboratory Abnormalities

  Number of participants with clinically significant abnormal laboratory findings for hematology, coagulation, serum chemistry, and urinalysis.

  Day -45 up to Day 28

• Mean Diastolic Blood Pressure at Baseline

  Baseline

• Percent Change In Diastolic Blood Pressure From Baseline To Day 28

  Diastolic blood pressure measurements were measured at specific time points.

  Day 1 (10, 20, 30, 45, and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28

• Mean Systolic Blood Pressure at Baseline

  Baseline

• Percent Change In Systolic Blood Pressure From Baseline To Day 28

  Systolic blood pressure measurements were measured at specific time points.

  Day 1 (10, 20, 30, 45, and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28

• Mean Oral Body Temperature at Baseline

  Baseline

• Percent Change In Oral Body Temperature From Baseline To Day 28

  Body temperature measurements were measured at specific time points.

  Day 1 (45 and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28

• Mean Respiratory Rate at Baseline

  Baseline

• Percent Change In Respiratory Rate From Baseline To Day 28

  Respiratory rate measurements were measured at specific time points.

  Day 1 (45 and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28

• Mean Heart Rate at Baseline

  Baseline

• Percent Change In Heart Rate From Baseline To Day 28

  Heart rate measurements were measured at specific time points.

  Baseline, Day 1 (10, 20, 30, 45, and 60 minutes post-dose), Day 2, Day 3, Day 7, and Day 28

• Incidence Of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings

  Number of participants per cohort with clinically significant ECG findings.

  Up to Day 28

• Participants Experiencing Anti-drug Antibodies (ADAs)

  Number of participants who developed ADAs to PB2452.

  Day -3, Day 1, Day 7, and Day 28

• Number of Participants With Adverse Events During Physical Examination

  Participants with adverse events noted during physical exam between baseline and end of study.

  Baseline through Day 28

Study Arms (5)

1: 18 g PB2452 or Placebo (Ticagrelor Pre-Trx)

EXPERIMENTAL

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

Drug: Ticagrelor Oral Tablet - Pre-Treatment; Drug: PB2452 Infusion; Drug: Placebo - Sodium Chloride

2: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

EXPERIMENTAL

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

Drug: Ticagrelor Oral Tablet - Pre-Treatment; Drug: PB2452 Infusion; Drug: Placebo - Sodium Chloride

3: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

EXPERIMENTAL

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

Drug: PB2452 Infusion; Drug: Placebo - Sodium Chloride; Drug: Ticagrelor Oral Tablet - Pre-Treatment

4: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

EXPERIMENTAL

PB2452 Infusion or Placebo - Sodium Chloride With Ticagrelor Oral Tablet: 180 mg BID for a total of 5 doses

Drug: PB2452 Infusion; Drug: Placebo - Sodium Chloride; Drug: Ticagrelor Oral Tablet - Pre-Treatment

5: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

EXPERIMENTAL

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

Drug: PB2452 Infusion; Drug: Placebo - Sodium Chloride; Drug: Ticagrelor Oral Tablet - Pre-Treatment; Drug: Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment

Interventions

PB2452 Infusion DRUG

30 minute - 24 hour infusion

3: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx); 4: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx); 5: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

Placebo - Sodium Chloride DRUG

30 minute - 24 hour infusion

3: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx); 4: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx); 5: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

Ticagrelor Oral Tablet - Pre-Treatment DRUG

Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo

1: 18 g PB2452 or Placebo (Ticagrelor Pre-Trx); 2: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx); 5: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment DRUG

Ticagrelor 180 mg + 90 mg BID for 5 doses prior to PB2452 or Placebo and Ticagrelor 180 mg 24 hours following PB2452 or Placebo

5: 18 g or greater PB2452 or Placebo (Ticagrelor Pre-Trx)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject provides written informed consent and agrees to comply with all protocol requirements.
• The subject is male or female between 18 and 80 years of age, inclusive (50 to 80 years for Cohorts 1-2, 18 to 50 years for Cohorts 3-5).
• The subject has a body mass index (BMI) between 18 and 35 kg/m2 and a weight of ≥50 kg but ≤120 kg, inclusive, at Screening.

You may not qualify if:

• Hypertension (HTN) controlled with ≤2 antihypertensive drugs
• Diabetes controlled with diet/exercise or treated with up to 2 oral diabetes medications
• Subjects with diabetes must have a glycated hemoglobin HbA1c ≤8 mg/dL at Screening.
• Mild hepatic enzyme elevation (aspartate aminotransferase (AST) or alanine transaminase (ALT) \<1.5 x ULN or total bilirubin \<1.2 x ULN)
• Controlled hyperlipidemia (defined with a Screening low density lipoprotein LDL \<160 mg/dL)
• White blood cell (WBC) count, platelet count, hemoglobin (Hgb) level within normal range, as defined by the clinical laboratory
• Thyroid stimulating hormone (TSH) level within normal range, as defined by the clinical laboratory at Screening
• Prothrombin time (PT) and partial thromboplastin time (PTT) level within normal range, as defined by the clinical laboratory
• Subjects taking medications for well-controlled medical conditions must have been on a stable dose (meaning no changes in dose) for at least 30 days prior to Screening visit.
• Older and elderly subjects entering the study who are not already taking daily ASA must be willing to start an 81 mg daily dose of ASA on Day -7 and continue daily dosing until the final dose is administered on the morning of Day 1. Subjects entering the study who are already taking ASA daily will be administered 81 mg ASA daily between Day -7 and Day 1 and must suspend further ASA dosing until discharge from the clinical facility.
• Female subjects of childbearing potential must not be pregnant, lactating, or planning to become pregnant for 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 from 30 days before study drug administration through to the end of the study.
• Effective birth control methods include oral, implantable, patch, or injectable contraceptive hormone treatment, hormone-containing intrauterine device that has been in place ≥2 months prior to Screening, sponge, diaphragm, or cervical cap with spermicidal gel or cream for female subjects or condom or vasectomy for male subjects.
• Women are considered to not be of childbearing potential if they have fulfilled one of these criteria: documentation of irreversible surgical sterilization (i.e., hysterectomy or bilateral oophorectomy \[not tubal ligation\]) or are postmenopausal (defined as amenorrhea for 12 consecutive months following cessation of all exogenous hormonal treatments, and documented plasma follicle-stimulating hormone (FSH) 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 refrain from donating sperm for ≥90 days following the last dose of study drug.
• Concern the subject may be unable 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

Sponsors & Collaborators

• SFJ Pharmaceuticals, Inc.: lead

Study Sites (1)

PPD

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

Aftercare

Intervention Hierarchy (Ancestors)

Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services; Primary Health Care; Comprehensive Health Care; Patient Care Management; Health Services Administration

Results Point of Contact

• Title: Michele LaRussa SVP, Chief Regulatory Officer
• Organization: SFJ Pharmaceuticals, Inc.

Bentracimab.General@SFJ-Pharma.com

925-223-6233

Study Officials

• LuAnn Bundrant, MD

  PPD Development, LP

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: April 24, 2019
• First Posted: April 26, 2019
• Study Start: April 16, 2019
• Primary Completion: October 9, 2019
• Study Completion: October 9, 2019
• Last Updated: May 1, 2024
• Results First Posted: May 1, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)