To Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of LYNC-101 for Injection in Healthy Adult Participants

LyncBio Therapeutics Co., Ltd.

Status and phase: Begins enrollment in 1 month; Phase 1

Conditions: UC - Ulcerative Colitis

Treatments: Drug: LYNC-101; Drug: LYNC-101 Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07505030

LYNC-101-I-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 60 days old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy male or female participants aged 18-60 years (inclusive).
2. Body weight ≥ 50 kg for males and ≥ 45 kg for females, with a body mass index (BMI) of 18-32 kg/m² (inclusive).
3. Able to fully understand the study, voluntarily agree to participate in the study, and sign the informed consent form.
4. 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

1. 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.
2. 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).
3. 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.
4. History of childhood asthma (regardless of resolution), depression, migraine, or Gilbert's Syndrome. Note: Participants with a history of cholecystectomy are eligible for inclusion.
5. 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.
6. Participants who have received major surgery within 4 weeks prior to screening or will receive planned surgery during the study period.
7. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) at Screening or Day -1. Repeat testing at Screening and Day -1 is acceptable for out-of-range values following approval by the PI or delegate.
8. Participants with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2(using Cockroft & Gault formula). And a repeat sample is allowed if required.
9. Participants with known history of hypersensitivity, allergic constitution, or allergy to any ingredient of the IMP.
10. Participants who have participated in other clinical studies and have received the IMP within 30 days or 5 half-lives (whichever is longer) prior to screening.
11. Participants who have received treatment with any marketed or investigational biologic agent within 4 months or 5 half-lives (whichever is longer) prior to screening.
12. Participants who have received any prescription drugs (excluding contraception), over-the-counter medications (excluding paracetamol), herbal products, or dietary supplements (excluding vitamin products) within 2 weeks or 5 half-lives (whichever is longer) prior to screening.
13. Participants who have received or will receive any systemic cytotoxic or immunosuppressive agent within 6 months prior to screening or during the study, or any topical cytotoxic or immunosuppressive agent within 30 days or 5 half-lives (whichever is longer) prior to screening or during the study.
14. Participants who have received B-cell or T-cell depleting agents (e.g., rituximab) within 6 months prior to screening.
15. Participants who have been vaccinated 4 weeks prior to first dose or plan to be vaccinated during the study.
16. Participants who have received immunoglobulins or blood products within 30 days prior to screening.
17. Participants who have experienced blood loss or blood donation exceeding 400 mL within 3 months prior to screening.
18. Participants with no ability to tolerate venipuncture, or with history of difficult blood collection, history of vasovagal syncope related to blood draws, or poor venous access.
19. Participants who smoke > 5 cigarettes per day (or equivalent use of other nicotine-containing products) within 6 months prior to screening, or are unable to refrain from tobacco use during the study.
20. Participants who have an alcohol consumption exceeding 14 units per week (1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine) within 3 months prior to screening, or are unable to abstain from alcohol at least 24 hours before each Study Site admission and each outpatient visit and throughout the duration of each Study Site visit, or have a positive alcohol breath test at screening or Day -1, and a repeat test is allowed if required.
21. Participants with a history of drug abuse or positive urine drug screening or Day -1, and a repeat test is allowed if required.
22. Participants who are unable to refrain from consuming xanthine-rich beverages (e.g., chocolate, coffee, tea), foods (e.g., animal liver), or fruits/juices known to affect drug metabolism (e.g., grapefruit, pomelo, star fruit) from 3 days before dosing through the confinement period; or are unable to avoid strenuous exercise from 48 hours before dosing through the confinement period; or have any other behavior that could significantly affect drug absorption, distribution, metabolism, or excretion.
23. Female participants who are pregnant, breastfeeding.
24. Female participants of childbearing potential with positive pregnancy test at screening or Day -1.
25. Participants with any other condition that, as assessed by the Investigator, would pose a safety risk to the participant, interfere with the study conduct, or compromise the participant's ability to complete the study or comply with relevant requirements.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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50 participants in 7 patient groups

SAD:dose 1

Experimental group

Description:

1 receiving LYNC-101 for Injection and 1 receiving placebo

Treatment:

Drug: LYNC-101 Placebo

Drug: LYNC-101

SAD:dose2

Experimental group

Description:

6 to receive LYNC-101 for Injection and 2 to receive placebo

Treatment:

Drug: LYNC-101 Placebo

Drug: LYNC-101

SAD:dose3

Experimental group

Description:

6 to receive LYNC-101 for Injection and 2 to receive placebo

Treatment:

Drug: LYNC-101 Placebo

Drug: LYNC-101

SAD:dose4

Experimental group

Description:

6 to receive LYNC-101 for Injection and 2 to receive placebo

Treatment:

Drug: LYNC-101 Placebo

Drug: LYNC-101

SAD:dose5

Experimental group

Description:

6 to receive LYNC-101 for Injection and 2 to receive placebo

Treatment:

Drug: LYNC-101 Placebo

Drug: LYNC-101

MAD:dose1

Experimental group

Description:

6 to receive LYNC-101 for Injection and 2 to receive placebo

Treatment:

Drug: LYNC-101 Placebo

Drug: LYNC-101

MAD:dose2

Experimental group

Description:

6 to receive LYNC-101 for Injection and 2 to receive placebo

Treatment:

Drug: LYNC-101 Placebo

Drug: LYNC-101