A Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of 9MW3811 in Healthy Subjects

Study Overview
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Brief Summary
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This is a first-in-human, single ascending dose study of 9MW3811, the primary objective of which is to evaluate the safety and tolerability of 9MW3811 in healthy adult participants.

Detailed Description
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The single ascending dose study will comprise 4 dose cohorts of 8 healthy participants each. In each cohort, participants will be randomized to receive 9MW3811 or placebo by 6:2.

Official Title
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A Phase 1, First-in-human, Randomized, Double-blind，Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, Pharmacodynamics and Immunogenicity of 9MW3811 in Healthy Adult Participants

Conditions
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Pulmonary Fibrosis, Tumor

Intervention / Treatment
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* Drug: 9MW3811 injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants between 18 and 55 years of age, inclusive. Male body weight ≥50.0 kg, or female body weight ≥45.0 kg, and body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive. In good health determined by the investigator based on a medical evaluation, including a detailed medical and surgical history, as well as a complete physical examination including vital signs, 12-lead ECG, laboratory evaluations. Exclusion Criteria: Clinically significant histories determined by the investigator of cardiovascular, hepatic, renal, gastrointestinal, neurological, respiratory, hematological, endocrinological, immunological, metabolic, and musculoskeletal abnormalities. Having any history of an allergy to biological agents or any components of study drug; those who have a history of allergies and judged by the investigator to be ineligible for enrolment. Use of any prescription medication 14 days prior to dosing or over-the-counter medication, vitamins, and/or herbal medicines 7 days prior to dosing (Excluding oral contraception, occasional paracetamol, ibuprofen and standard dose of multivitamins at the discretion of the PI or designee) Participants who have been vaccinated within 4 weeks prior to screening or who are scheduled to be vaccinated during the study Participants who received immunosuppressants except for previous use of inhaled or nasal corticosteroids 4 weeks earlier before administration or any oral corticosteroids 8 weeks earlier before administration, and who had received a single dose of monoclonal antibodies for any reason within 1 year prior to screening Participants with one or more clinically significant positive test results of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody History of drug abuse including narcotic and psychiatric drugs within 6 months prior to screening or a positive drug abuse test result at baseline (Morphine, Methamphetamine, Tetrahydrocannabinol acid, Cocaine) Participants with a positive SARS-CoV-2 test prior to admission (polymerase chain reaction (PCR) and/or rapid antigen testing (RAT), per site policy and PI discretion)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 9MW3811 injection<br>single dose escalation for experimental drug | Drug: 9MW3811 injection<br>* Single dose intravenously infused on day 1<br>|
| Placebo Comparator: placebo<br>matching placebo administration for control | Drug: Placebo<br>* Single dose of matching placebo intravenously infused on day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) as assessed by CTCAE v5.0 | An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | up to Day113 | 
| Number of participants with abnormal clinically significant results from physical examination | The physical examinations will include examination of the following: head, eyes, ears, nose and throat, neck (including thyroid & nodes), cardiovascular system, dermatological system, musculoskeletal system, respiratory system, gastrointestinal system, neurological system and renal system. | up to Day113 | 
| Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters | The examination indicators include heart rate, PR, QRS, uncorrected QT, and QTcF [corrected by Fridericia formula, QTcF = QT/(RR^0.33), RR is the standardized heart rate value, which is obtained by dividing 60 by the heart rate]. | up to Day113 | 
| Number of participants with abnormally clinical vital signs | Vital signs measurements will include pulse rate, respiration rate, blood pressure (systolic and diastolic blood pressure) and body temperature. | up to Day113 | 
| Number of participants with abnormal clinically significant clinical laboratory results | Clinical laboratory tests include hematology, urinalysis, blood chemistry, coagulation function. | up to Day113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) | To determine the pharmacokinetic (PK) of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| Time to reach Cmax (Tmax) | To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| Area under the plasma concentration versus time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t) | To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| Terminal elimination half-life (t1/2) | To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| AUC from time 0 extrapolated to infinity (AUC0-inf) | To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| Terminal elimination rate constant (λz) | To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| Apparent clearance (CL) | To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| Volume of distribution (Vz) | To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants. | up to Day 113 | 
| Incidence of antidrug antibodies (ADA) at specified timepoints relative to baseline | To determine the immunogenicity of 9MW3811. | up to Day 113 |