A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of LYNC-101 for Injection in Healthy Adult Participants
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- LyncBio Therapeutics Co., Ltd.
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and treatment-emergent adverse events (TEAEs)
Overview
Brief Summary
This Phase I study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and cytokine profiles of LYNC-101 for Injection in healthy adult participants. The study consists of 2 parts: Part 1 is a single ascending dose (SAD) study and Part 2 is a multiple ascending dose (MAD) study. In Part 1, participants will receive a single intravenous infusion of LYNC-101 for Injection or placebo across sequential ascending dose cohorts. In Part 2, participants will receive intravenous infusions of LYNC-101 for Injection or placebo once every 3 weeks for a total of 3 doses across sequential ascending dose cohorts.
Detailed Description
Part 1: Single Ascending Dose (SAD) Part 1 is designed to evaluate the safety, tolerability, PK, PD, immunogenicity, and cytokine profiles of a single intravenous dose of LYNC-101 for Injection in healthy adult participants.
Eligible participants will be sequentially enrolled into 5 ascending dose groups: 1 mg/kg, 2.5 mg/kg, 4 mg/kg, 6 mg/kg, and 8 mg/kg. Group 1 will enroll 2 participants randomized to receive LYNC-101 for Injection or placebo. Groups 2 through 5 will each enroll 8 participants, randomized so that 6 participants receive LYNC-101 for Injection and 2 participants receive placebo.
Participants will be admitted to the Phase I clinical study site on Day -1 and will receive a single intravenous infusion of LYNC-101 for Injection or placebo on Day 1. Participants will remain at the study site through Day 5 and may be discharged after completion of safety and blood sampling assessments, with investigator approval. Participants will return for follow-up assessments and blood sampling on Days 8, 11, 15, 22, 29, 36, and 43 after dosing.
Sentinel dosing will be implemented in all dose groups except Group 1. In each applicable cohort, the first 2 participants will be randomized in a 1:1 ratio to receive LYNC-101 for Injection or placebo. If no significant safety concerns are identified within 72 hours after dosing in the sentinel participants, the remaining participants in the cohort will be randomized in a ratio of 5:1 to receive LYNC-101 for Injection or placebo.
Dose escalation will proceed stepwise from the lowest dose level. The Safety Review Committee (SRC) will review safety, tolerability, and available PK data through Day 15 after dosing of the last participant in each cohort to determine whether escalation to the next dose level may proceed.
Part 2: Multiple Ascending Dose (MAD) Part 2 is designed to evaluate the safety, tolerability, PK, PD, immunogenicity, and cytokine profiles of multiple intravenous doses of LYNC-101 for Injection in healthy adult participants.
Eligible participants will be sequentially enrolled into 2 ascending dose groups, tentatively planned as 3 mg/kg and 4 mg/kg, with dose levels subject to adjustment based on results from the SAD part. Approximately 16 participants are planned in total. Each cohort will include 8 participants randomized in a 3:1 ratio to receive LYNC-101 for Injection or placebo, such that 6 participants receive LYNC-101 for Injection and 2 participants receive placebo.
Participants will receive study treatment once every 21 days for a total of 3 doses on Days 1, 22, and 43. Participants will be admitted on Day -1 before each dosing period and discharged after completion of post-dose safety and blood sampling assessments, with investigator approval.
The SRC will review safety, tolerability, and available PK data through Day 57 after the last dose of the last participant in each cohort to determine whether escalation to the next dose level may proceed.
Based on accumulated safety, tolerability, and PK data, the Investigator and Sponsor may modify the study design, including dose levels, post-dose observation periods, timing of safety assessments, and PK/PD/immunogenicity/cytokine sampling schedules.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Days to 60 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy male or female participants aged 18-60 years (inclusive).
- •Body weight ≥ 50 kg for males and ≥ 45 kg for females, with a body mass index (BMI) of 18-32 kg/m² (inclusive).
- •Able to fully understand the study, voluntarily agree to participate in the study, and sign the informed consent form.
- •Participants agree to have no plans for conception, sperm donation, or egg donation from the date of signing the informed consent form until 3 months after the last dose and must use effective non-pharmacological contraception with partners of childbearing potential.
Exclusion Criteria
- •Participants with clinically significant abnormalities (as judged by the PI or delegate) in vital signs, physical examinations, laboratory tests, or 12-lead ECG during the screening period.
- •Participants with positive test result for any of the following: hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or treponema pallidum-specific antibody (TP-Ab).
- •Participants with history or current presence of any clinically significant disease or disorder of the circulatory, endocrine, metabolic, urinary, digestive, dermatologic, hematologic, nervous, or psychiatric systems, which, as assessed by the Investigator, precludes safe participation in the study.
- •History of childhood asthma (regardless of resolution), depression, migraine, or Gilbert's Syndrome. Note: Participants with a history of cholecystectomy are eligible for inclusion.
- •Participants with history of clinically significant infection (including upper or lower respiratory tract infection) requiring antibiotic or antiviral treatment within 14 days prior to or during screening, in the opinion of the PI or delegate.
- •Participants who have received major surgery within 4 weeks prior to screening or will receive planned surgery during the study period.
- •Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) \>1.5 × upper limit of normal (ULN) at Screening or Day -
- •Repeat testing at Screening and Day -1 is acceptable for out-of-range values following approval by the PI or delegate.
- •Participants with estimated glomerular filtration rate (eGFR) \< 90 mL/min/1.73m2(using Cockroft \& Gault formula). And a repeat sample is allowed if required.
- •Participants with known history of hypersensitivity, allergic constitution, or allergy to any ingredient of the IMP.
Arms & Interventions
MAD:dose2
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 (Drug)
MAD:dose2
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 Placebo (Drug)
SAD:dose 1
1 receiving LYNC-101 for Injection and 1 receiving placebo
Intervention: LYNC-101 (Drug)
SAD:dose 1
1 receiving LYNC-101 for Injection and 1 receiving placebo
Intervention: LYNC-101 Placebo (Drug)
SAD:dose2
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 (Drug)
SAD:dose2
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 Placebo (Drug)
SAD:dose3
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 (Drug)
SAD:dose3
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 Placebo (Drug)
SAD:dose4
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 (Drug)
SAD:dose4
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 Placebo (Drug)
SAD:dose5
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 (Drug)
SAD:dose5
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 Placebo (Drug)
MAD:dose1
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 (Drug)
MAD:dose1
6 to receive LYNC-101 for Injection and 2 to receive placebo
Intervention: LYNC-101 Placebo (Drug)
Outcomes
Primary Outcomes
Incidence and severity of adverse events (AEs), serious adverse events (SAEs), and treatment-emergent adverse events (TEAEs)
Time Frame: SAD groups: up to 43 days; MAD groups: up to 85 days
Changes in 12-lead electrocardiogram parameters (ECG QT Interval, etc)
Time Frame: SAD groups: up to 43 days; MAD groups: up to 85 days
Heart rate (HR), PR interval, QT interval, QRS interval, and QTcF interval should be recorded. During the screening period, if an abnormal corrected QT interval (QTcF) is determined by the Investigator, it may be re-measured up to 2 times, with a recommended interval of at least 5 minutes between each measurement, and the average QTcF value of the three measurements should be calculated. QTcF = QT/(RR\^0.33), RR = 60 / HR. During the study, the Investigator will determine whether a repeat measurement is necessary.
Changes in vital signs (Number of participants with treatment-related adverse events as assessed by CTCAE v6.0)
Time Frame: SAD groups: up to 43 days; MAD groups: up to 85 days
Including sitting blood pressure, respiration, pulse, and body temperature (axillary, tympanic, or forehead temperature are all acceptable, but participants at the same study site must use a consistent method). Vital signs will be measured at the times specified in the study schedule. Additional vital sign tests may be performed during the study if abnormalities are clinically significant.
Changes in physical examination findings (Number of participants with treatment-related adverse events as assessed by CTCAE v6.0)
Time Frame: SAD groups: up to 43 days; MAD groups: up to 85 days
Physical examinations will be conducted according to the study assessment schedule. Comprehensive physical examinations include general condition (including overall appearance, skin, mucous membranes, lymph nodes, etc.), head, neck, chest, abdomen, spine and extremities, and nervous system, and other.
Changes in clinical laboratory test results(Number of participants with treatment-related adverse events as assessed by CTCAE v6.0)
Time Frame: SAD groups: up to 43 days; MAD groups: up to 85 days
Laboratory tests shall be performed according to the study assessment schedule. The Investigator must evaluate all values outside the normal range (CS: clinically significant; NCS: not clinically significant) and sign with their name and date. Only abnormalities judged by the Investigator as CS and meeting the definition of AE shall be recorded as an AE. In this study, the Investigator may, at their own discretion, perform additional or repeated tests if deemed necessary.
Secondary Outcomes
- Maximum observed plasma concentration (Cmax) of LYNC-101(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Time to maximum observed plasma concentration (Tmax) of LYNC-101(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Area under the plasma concentration-time curve from time 0 to 504 hours (AUC0-504h)(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t)(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Apparent volume of distribution (Vz)(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Plasma clearance (CL)(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Plasma elimination half-life (t1/2)(SAD groups: up to 43 days; MAD groups: up to 85 days)
- Time to maximum concentration at steady state (Tmax,ss)(MAD groups only: up to 85 days)
- Maximum concentration at steady state (Cmax,ss)(MAD groups only: up to 85 days)
- Trough concentration at steady state (Cmin,ss)(MAD groups only: up to 85 days)
- Mean concentration at steady state (Cav,ss)(MAD groups only: up to 85 days)
- Area under the steady-state plasma concentration-time curve (AUCss)(MAD groups only: up to 85 days)
- Accumulation ratio (Rac)(MAD groups only: up to 85 days)
- Incidence and characteristics of anti-drug antibodies (ADAs)(SAD groups: up to 43 days; MAD groups: up to 85 days)