Healthy Participants Randomized, Double-blind, Placebo-controlled, Phase Ⅰ

A Phase Ⅰ Randomized, Double-blind, Placebo-controlled, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of BY002 in Healthy Participants

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

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants Study
• Intervention / Treatment: Drug: Placebo; Drug: BY002

Detailed Description

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
• Enrollment (Estimated): 104
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jian Liu; Phone Number: 0571-87236560; Email: lindaliu87@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 31003
      • Recruiting
      • The First Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Jian Liu; Phone Number: 0571-87236560; Email: lindaliu87@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1. Male or female aged ≥18 years at the time of signing the Informed Consent Form (ICF).

  2. At screening, body mass index (BMI) between 18 and 30 kg/m² (inclusive), with weight ≥50.0 kg for males and ≥45.0 kg for females.

  3. Good health status determined by screening examinations. Good health status is defined as: absence of clinically relevant abnormalities or psychiatric diseases that, in the investigator's judgment, could compromise participant safety, affect the scientific validity of the study, expose the participant to unacceptable risk, or interfere with their compliance with study procedures and restrictions.

  4. Male participants and their partners of childbearing potential must agree to use highly effective contraception during the study and for at least 12 weeks after the last dose. Male participants must refrain from donating sperm during this period. Female participants must not be pregnant or lactating. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening and be willing to use highly effective contraception throughout the study and for at least 12 weeks after the last dose. Female participants must avoid donating eggs during this period.

  5. Participants who, after capsaicin challenge during screening, meet the criteria specified in the Capsaicin Challenge Test Operating Manual (applicable only to participants undergoing the capsaicin challenge test).

  6. Provide written informed consent before any study-related procedures are performed.

Exclusion Criteria:

• 1. Individuals with a history or current presence of clinically significant cardiovascular (e.g., hypertension), pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, musculoskeletal, rheumatologic, psychiatric, systemic, ocular, reproductive, otorhinolaryngological, dermatological, or infectious diseases, or acute disease signs, unless deemed not clinically significant by the investigator and sponsor.

  2. Individuals who have donated blood (≥400 mL) or experienced significant blood loss (≥400 mL), donated ≥2 units of blood components, or received a blood transfusion within 2 months prior to the first dose of investigational drug; or who plan to donate blood during the study.

  3. Individuals with allergic constitution (defined as a clear history of allergy to two or more drugs, or to two or more common foods, or to common inhaled/contact irritants such as pollen, dust mites, pet dander, mold, etc.), or a known history of allergic reactions to any therapeutic protein drugs (including monoclonal antibodies, fusion proteins, recombinant enzymes, cytokines, peptide hormones, blood products, vaccines, etc.).

  4. Participants who are known to be allergic to any component of the investigational drug product or to capsaicin (applicable only to participants undergoing the capsaicin challenge test), or who have other contraindications.

  5. Alcohol abuse or frequent alcohol consumption within 6 months prior to screening, defined as weekly alcohol intake exceeding 14 units (1 unit = 360 mL of beer, 45 mL of 40% spirits, or 150 mL of wine), or unwillingness to abstain from alcohol and any alcohol-containing products during the study; or a positive alcohol breath test.

  6. History of drug abuse within 12 months prior to screening, or positive urine drug screen result.

  7. Smokers (defined as consuming more than 5 cigarettes or equivalent products per week), or those who cannot discontinue the use of any tobacco products during the study period.

  8. The investigator determines that the participant's skin characteristics are unsuitable for capsaicin skin challenge (applicable only to participants undergoing the capsaicin challenge test).

  9. Participants for whom venous blood collection is difficult.

  10. Individuals who, as judged by the investigator, have clinically significant abnormalities in physical examination, vital signs, ECG, clinical laboratory tests (hematology, blood biochemistry, urinalysis, coagulation function), or chest X-ray at screening.

  11. Individuals with a QT interval corrected using Fridericia's formula (QTcF) >450 ms for male participants or >470 ms for female participants on the screening electrocardiogram (ECG).

  12. Positive result in any of the following tests: Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV) antibody, anti-human immunodeficiency virus antibody (anti-HIV Ab), and specific antibody to Treponema pallidum (TP-Ab).

  13. Individuals who have used any prescription medication, over-the-counter (OTC) drugs, traditional Chinese patent medicines, Chinese herbal medicines, vitamins, or dietary supplements within 14 days prior to the first dose or within 5 elimination half-lives or pharmacodynamic half-lives (whichever is longer) that may interfere with the study assessments.

  14. Receipt of any vaccine within 2 weeks prior to the first dose of the investigational drug.

  15. Individuals who have enrolled in or participated in any clinical trial containing investigational drugs or other medical research within 1 month prior to the first dose, or within 5 elimination half-lives (whichever is longer).

  16. Individuals deemed by the investigator to be likely noncompliant during the study period, or unable to cooperate due to language barriers or intellectual disability, or otherwise unsuitable for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Capsaicin challenge test-placebo; During the SAD/MAD dose escalation phase, based on accumulated safety and pharmacokinetic (PK) data, the SRC will decide whether to initiate the capsaicin challenge test (conducting the single-dose and multiple-dose capsaicin challenge tests, respectively) and select the dose cohorts. Eight healthy participants will be randomized into each cohort, of whom 6 will receive the selected dose of BY002 and 2 will receive a placebo.	Drug: Placebo; Placebo, administered via subcutaneous (SC) injection as single or multiple doses according to the clinical trial protocol.
Placebo Comparator: Multiple Ascending Dose (MAD)-placebo; Based on the safety, tolerability, PK, PD, and other data obtained from the SAD study, 2-3 doses will be selected during the SAD dose escalation phase for further evaluation in the MAD study. Each cohort is planned to enroll 8 healthy participants, who will be randomized to the BY002 or placebo group in a 3:1 ratio.	Drug: Placebo; Placebo, administered via subcutaneous (SC) injection as single or multiple doses according to the clinical trial protocol.
Placebo Comparator: Single Ascending Dose (SAD)-placebo; The SAD study will consist of 6 dose cohorts (10 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg), with a planned enrollment of 48 healthy participants who will be randomized to the BY002 or placebo group in a 3:1 ratio. The SAD study will initiate with the lowest dose cohort and proceed sequentially. In each dose cohort, 8 healthy participants will be randomized in a double-blind manner, of whom 6 will receive BY002 and 2 will receive a placebo. A sentinel dosing strategy will be utilized for each dose cohort, whereby 2 participants will be enrolled first to receive a subcutaneous injection of BY002 or placebo. At least 24 hours post-dose, if safety is confirmed by the investigator, the remaining participants in the same dose-level cohort may proceed with enrollment and receive the investigational product according to the study design and methodology.	Drug: Placebo; Placebo, administered via subcutaneous (SC) injection as single or multiple doses according to the clinical trial protocol.
Experimental: Capsaicin challenge test; During the SAD/MAD dose escalation phase, based on accumulated safety and pharmacokinetic (PK) data, the SRC will decide whether to initiate the capsaicin challenge test (conducting the single-dose and multiple-dose capsaicin challenge tests, respectively) and select the dose cohorts. Eight healthy participants will be randomized into each cohort, of whom 6 will receive the selected dose of BY002 and 2 will receive a placebo.	Drug: BY002; BY002, administered via subcutaneous (SC) injection as single or multiple doses according to the clinical trial protocol.
Experimental: Multiple Ascending Dose (MAD); Based on the safety, tolerability, PK, PD, and other data obtained from the SAD study, 2-3 doses will be selected during the SAD dose escalation phase for further evaluation in the MAD study. Each cohort is planned to enroll 8 healthy participants, who will be randomized to the BY002 or placebo group in a 3:1 ratio.	Drug: BY002; BY002, administered via subcutaneous (SC) injection as single or multiple doses according to the clinical trial protocol.
Experimental: Single Ascending Dose (SAD); The SAD study will consist of 6 dose cohorts (10 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg), with a planned enrollment of 48 healthy participants who will be randomized to the BY002 or placebo group in a 3:1 ratio. The SAD study will initiate with the lowest dose cohort and proceed sequentially. In each dose cohort, 8 healthy participants will be randomized in a double-blind manner, of whom 6 will receive BY002 and 2 will receive a placebo. A sentinel dosing strategy will be utilized for each dose cohort, whereby 2 participants will be enrolled first to receive a subcutaneous injection of BY002 or placebo. At least 24 hours post-dose, if safety is confirmed by the investigator, the remaining participants in the same dose-level cohort may proceed with enrollment and receive the investigational product according to the study design and methodology.	Drug: BY002; BY002, administered via subcutaneous (SC) injection as single or multiple doses according to the clinical trial protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence 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.	7 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pharmacokinetics (PK) analysis	Time to maximum observed plasma concentration	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.	7 days after the last dose
Measurement of immunogenicity of BY002.	Development of anti-drug antibodies (ADA) post-dose.	7 days after the last dose
pharmacokinetics (PK) analysis	Maximum observed plasma concentration	7 days after the last dose
pharmacokinetics (PK) analysis	Area under the concentration-time curve from time zero to the last measurable concentration	7 days after the last dose
pharmacokinetics (PK) analysis	Area under the concentration-time curve from time zero extrapolated to infinity	7 days after the last dose
pharmacokinetics (PK) analysis	Terminal elimination half-life	7 days after the last dose
pharmacokinetics (PK) analysis	Apparent volume of distribution (after non-intravenous administration)	7 days after the last dose
pharmacokinetics (PK) analysis	Mean residence time (MRT)	7 days after the last dose
pharmacokinetics (PK) analysis	Terminal elimination rate constant	7 days after the last dose
pharmacokinetics (PK) analysis	Percentage of extrapolated area under the curve	7 days after the last dose

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: SDM Bioservices Inc.; Beijing Hikinge Pharmaceutical Technology Co., Ltd.; Biyopharma Co., LTD，Hangzhou， China

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: May 30, 2026
• First Submitted That Met QC Criteria: June 5, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: BY002-161

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No