A Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BGB149 Following Single Dose Administration in Healthy Subjects

BerGenBio ASA1 site in 1 country24 target enrollmentDecember 19, 2018

ConditionsHealthy Volunteers

Overview

Phase: Early Phase 1
Intervention: Not specified
Conditions: Healthy Volunteers
Sponsor: BerGenBio ASA
Enrollment: 24
Locations: 1
Primary Endpoint: Incidence of treatment-emergent clinical adverse events (AE) following single intravenous (IV) administration of BGB149 or matched placebo
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This clinical trial is a Phase I, first-in-human. The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of BGB149 after single IV doses in healthy male and female subjects. Multiple dose levels will be explored.

Registry

clinicaltrials.gov

Start Date

December 19, 2018

End Date

October 31, 2019

Last Updated

4 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

BerGenBio ASA

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•The subject voluntarily agrees to participate in this study and signs an Independent Ethics Committee approved informed consent form prior to performing any of the screening procedures.
•Healthy male and female subjects, between 18 to 55 years of age, inclusive, at the screening visit.
•If male, Must agree to use appropriate double-barrier contraception and to refrain from donating sperm from the time of dosing until 3 months after dosing.
•If female, Must be of non-childbearing potential (surgically sterile \[hysterectomy or bilateral tubal ligation\] or postmenopausal ≥ 1 year with follicle stimulating hormone \> 40 IU/L).
•Body mass index between 18.0 and 30.0 kg/m2, inclusive, at the screening visit with a weight of at least 50kg.
•Non-smoker, defined as a subject who has not smoked previously and/or who has discontinued smoking or the use of nicotine/nicotine-containing products (including snuff and similar products) at least 3 months before the screening visit.
•Subjects are in good health, as determined by medical history, physical examination, vital signs assessment, resting 12-lead ECG and clinical laboratory evaluations within normal reference ranges or outside of normal reference ranges considered not clinically relevant by the Principal Investigator or designee.
•Subject must have suitable veins for cannulation and/or repeated venipuncture.

Exclusion Criteria

•Female subjects of childbearing potential, or breastfeeding, or have a positive serum pregnancy test at the screening visit or a positive urine pregnancy test on admission.
•A positive urine cotinine result (\>500ng/mL) at the screening visit or on admission.
•Subjects who have ongoing or significant history of alcoholism or drug/chemical abuse in the past 5years, as determined by the Principal Investigator or designee.
•Subjects who have positive urine drugs of abuse screen at the screening visit or on admission, or a positive urine alcohol test at the screening visit or on admission.
•Subjects who are unwilling to avoid the use of alcohol within 48 hours before any study visit and while confined to the study center.
•Subjects who are unwilling to abstain from heavy physical training from 7 days before first dosing until the final follow-up visit.
•Subjects who have used the following: Any prescribed medication within 14 days prior to planned time of dosing. Non-prescription or over-the-counter medication, herbal and dietary supplements such as St John's Wort, vitamins and minerals that could affect the outcome of the study within 1 week prior to planned time of dosing. Live attenuated vaccines and systemic corticosteroids within 3 months prior to planned time of dosing.
•Subjects who have donated blood in the 3 months prior to the screening visit, plasma in the 7 days prior to the screening visit or platelets in the 6 weeks prior to the screening visit.
•Subjects who have a history of significant drug allergy (e.g., anaphylaxis) or any clinically significant allergic condition (excluding non-active hay fever), as determined by the Principal Investigator or designee.
•Subjects who have had a clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of dosing, as determined by the Principal Investigator or designee.

Outcomes

Primary Outcomes

Incidence of treatment-emergent clinical adverse events (AE) following single intravenous (IV) administration of BGB149 or matched placebo

Time Frame: 85 days

Number of healthy volunteers experiencing adverse events (AE) AE categorized by grading for severity according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).

Frequency of treatment-emergent laboratory abnormalities following single intravenous (IV) administration of BGB149 or matched placebo

Time Frame: 85 days

Number of healthy volunteers experiencing clinically significant abnormalities of clinical laboratory tests (hematology, coagulation, clinical chemistry and urinalysis); categorized by grading for severity according to the CTCAE version 5.0.

Secondary Outcomes

Pharmacokinetic Parameters: BGB149 AUC(0-last), following single intravenous (IV) administration of BGB149 or matched placebo(up to 85 days)
Pharmacokinetic Parameters: BGB149 terminal elimination rate constant λz, following single intravenous (IV) administration of BGB149 or matched placebo(85 days)
Pharmacokinetic Parameters: BGB149 t½: Terminal elimination half-life, following single intravenous (IV) administration of BGB149 or matched placebo(85 days)
Immunogenicity indicators: anti-drug antibodies [ADA](85 days)
Pharmacokinetic Parameters: BGB149 Tmax following single intravenous (IV) administration of BGB149 or matched placebo(85 days)
Pharmacokinetic Parameters: BGB149 total body clearance (CL) following single intravenous (IV) administration of BGB149 or matched placebo(85 days)
Pharmacokinetic Parameters: BGB149 Cmax following single intravenous (IV) administration of BGB149 or matched placebo(85 days)
Pharmacokinetic Parameters: BGB149 AUC(0-infinity) following single intravenous (IV) administration of BGB149 or matched placebo(85 days)
Pharmacodynamics: detection of soluble Axl protein in circulation(85 days)
Immunogenicity indicators: neutralizing antibodies [NAb](85 days)