The objective of this clinical trial is to evaluate the safety and tolerability of BY002 in healthy subjects. Investigators will compare BY002 to a placebo (a pharmacologically inactive substance) to assess the safety and tolerability of BY002 in healthy subjects. Participants will undergo: 1. Single/multiple subcutaneous (SC) administrations of BY002/placebo 2. A 7-day safety follow-up period following the last dose
This first-in-human (FIH), randomized, double-blind, placebo-controlled Phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of BY002 (an investigational, bispecific tandem VHH antibody targeting the CGRP receptor) in healthy adult subjects. This Phase 1 study consists of two parts: a Single Ascending Dose (SAD) study and a Multiple Ascending Dose (MAD) study. Furthermore, both the SAD and MAD studies incorporate a capsaicin challenge test to assess the inhibitory effect of BY002 on capsaicin-induced elevation of dermal blood flow (DBF), serving as a PD marker for CGRP receptor antagonism.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
104
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGIncidence of adverse events (AEs), injection site reactions (ISRs), and serious adverse events (SAEs). [Safety and Tolerability]
Incidence of clinically significant abnormal changes in vital signs, physical examinations, laboratory evaluations, 12-lead electrocardiograms (12-lead ECGs), and other safety parameters.
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Time to maximum observed plasma concentration
Time frame: 7 days after the last dose
Measurement of capsaicin-induced cutaneous blood flow. (pharmacodynamic [PD] endpoint)
Area under the DBF curve (DBFAUC(t)) at each evaluation time point compared with placebo. Percentage inhibition of DBF.
Time frame: 7 days after the last dose
Measurement of immunogenicity of BY002.
Development of anti-drug antibodies (ADA) post-dose.
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Maximum observed plasma concentration
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Area under the concentration-time curve from time zero to the last measurable concentration
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Area under the concentration-time curve from time zero extrapolated to infinity
Time frame: 7 days after the last dose
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pharmacokinetics (PK) analysis
Terminal elimination half-life
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Apparent volume of distribution (after non-intravenous administration)
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Mean residence time (MRT)
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Terminal elimination rate constant
Time frame: 7 days after the last dose
pharmacokinetics (PK) analysis
Percentage of extrapolated area under the curve
Time frame: 7 days after the last dose