A Phase I Study of LY-CovMab Injection in Chinese Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
A single center, randomized, doubled-blind, placebo-control and single ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of LY-CovMab Injection in Chinese healthy subjects.

Detailed Description
-----------------
A single center, randomized, doubled-blind, placebo-control and single ascending dose phase I study: Primary objective: to evaluate the safety and tolerability of a single dose of LY-CovMab Injection in Chinese healthy subjects. Secondary objective: to evaluate the pharmacokinetics (PK) and immunogenicity of a single dose of LY-CovMab injection in Chinese healthy subjects.

Official Title
-----------------
A Phase I, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of LY-CovMab Injection in Chinese Healthy Subjects

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Drug: LY-CovMab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A signed informed consent form (ICF) from the patient or their legally authorized representative. Healthy males or females, ages ≥18 to ≤45 years. Male subjects with weight ≥50 kg, or female subjects with weight ≥45 kg, and body mass index (BMI) 19.0≤BMI≤26.0 kg/m2. No abnormality, or no clinically significant abnormality in vital signs, physical examination, laboratory tests, and 12-lead ECG in Chinese healthy subjects during the screening period. Female patients of childbearing potential (defined as female subjects who do not receive any operative sterilization or who had been through menopause for less than 1 year) must have a negative result for pregnancy test at screening. Male and female subjects with childbearing potential must agree to adopt effective contraceptive methods at least from 2 weeks prior to screening to 6 months after administration of the investigational drug. Exclusion Criteria: Those who have had surgery within 8 weeks prior to screening or who have surgery planned during the trial, and the investigator believes that such surgery may bring potential risks to the subjects. Prior to administration of the investigational drug, use of the following drugs or therapies: i. any prescription drug within 28 days. ii. any over-the-counter drug, including health care products within 7 days. Prior history or current evidence of serious disease or chronic disease of the respiratory system, circulatory system, digestive system, urinary system, reproductive system, nervous system, immune system, hematology, psychiatry, and dermatology, etc, or any disease that may interfere with the trial results. Subjects with coronavirus disease 2019 (COVID-19) or recovered from it or subjects positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid or serum SARS-CoV-2 specific antibodies. Subjects who are with known history of allergies to any ingredient of the investigational drug, or similar drugs, or subjects with allergic constitution (previously sensitive to ≥ 2 foods or drugs). Subjects with any positive test of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, treponema pallidum antibody, or human immunodeficiency virus (HIV) antibody. Subjects with alcohol abuse or tobacco abuse, or alcohol blood test results exceeding the upper limit of the normal range. Alcohol abuse is defined as: alcohol consumption of more than 14 U (1 U = 350 mL of beer, or 45 mL of liquor, or 150 mL of wine) per week within 3 months prior to screening. Tobacco abuse is defined as: smoking ≥5 cigarettes per day on average within 3 months prior to screening. Female subjects (including partners) who plan to be pregnant within one year upon screening, or pregnant or breast-feeding female subjects. Subjects with a history of drug addiction or drug abuse, or with positive urine screen test results for drug. Subjects donating whole blood or blood components, or with massive hemorrhage (>400 mL), within 3 months prior to screening. Prior vaccination with SARS-CoV-2 vaccine or participation in a SARS-CoV-2 neutralizing antibody clinical trial. Participation in any other clinical study with pharmacological intervention within 3 months prior to screening, or the drug is still within the elimination period (5 half-lives) prior to screening, whichever is longer. Vaccination within 12 weeks prior to screening, or planned vaccination during the study and within 12 weeks after the end of the study. Subjects with a history of fainting at the sight of blood or puncture. Subjects who are not suitable to participate in the clinical trial as considered by the investigator or cannot complete the study for any other reasons.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30mg LY-CovMab<br>LY-CovMab is diluted with 0.9% sodium chloride to a total volume of 250 mL for IV infusion | Drug: LY-CovMab<br>* single IV infusion<br>|
| Experimental: 150mg LY-CovMab<br>LY-CovMab is diluted with 0.9% sodium chloride to a total volume of 250 mL for IV infusion | Drug: LY-CovMab<br>* single IV infusion<br>|
| Experimental: 600mg LY-CovMab<br>LY-CovMab is diluted with 0.9% sodium chloride to a total volume of 250 mL for IV infusion | Drug: LY-CovMab<br>* single IV infusion<br>|
| Experimental: 1200mg LY-CovMab<br>LY-CovMab is diluted with 0.9% sodium chloride to a total volume of 250 mL for IV infusion | Drug: LY-CovMab<br>* single IV infusion<br>|
| Experimental: 2400mg LY-CovMab<br>LY-CovMab is diluted with 0.9% sodium chloride to a total volume of 250 mL for IV infusion | Drug: LY-CovMab<br>* single IV infusion<br>|
| Placebo Comparator: Placebo<br>Placebo is diluted with 0.9% sodium chloride to a total volume of 250 mL for IV infusion | Drug: LY-CovMab<br>* single IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Changes in Body Temperature | Grade of treatment-emergent changes in body temperature by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe). | up to 99 days | 
| Treatment-emergent Changes in Respiratory Rate | Grade of treatment-emergent changes in respiratory rate by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe). | up to 99 days | 
| Treatment-emergent Changes in Pulse Rate | Grade of treatment-emergent changes in pulse rate by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe). | up to 99 days | 
| Treatment-emergent Changes in Blood Pressure | Grade of treatment-emergent changes in blood pressure by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0. The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe). | up to 99 days | 
| Safety Laboratory Value (Haematology) | Haematology laboratory value by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0 (absolute and change from baseline where identified). The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe). | D-1, D4, D8, D15, D29, D50, D99 | 
| Safety Laboratory Value (blood chemistry) | Serum Chemistry laboratory value by Common Terminology Criteria for Adverse Event (CTCAE) scale version 5.0 (absolute and change from baseline where identified). The scale ranges from Grade 1 (Mild) to Grade 5 (Most Severe). | D-1, D4, D8, D15, D29, D50, D99 | 
| Frequency and Grade of Adverse Events |  | up to 99 days | 
| Assess safety profile of LY-CovMab | 12 lead electrocardiogram (ECG) heart rate | D-1, D4, D8, D15, D29, D50, D99 | 
| Assess safety profile of LY-CovMab | 12 lead electrocardiogram (ECG) PR interval | D-1, D4, D8, D15, D29, D50, D99 | 
| Assess safety profile of LY-CovMab | 12 lead electrocardiogram (ECG) QTc interval | D-1, D4, D8, D15, D29, D50, D99 | 
| Assess safety profile of LY-CovMab | 12 lead electrocardiogram (ECG) QRS interval | D-1, D4, D8, D15, D29, D50, D99 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess Pharmacokinetic parameters of LY-CovMab | Maximum observed concentration (Cmax) | up to 99 days | 
| Assess Pharmacokinetic parameters of LY-CovMab | Time to maximum observed concentration (Tmax) | up to 99 days | 
| Assess Pharmacokinetic parameters of LY-CovMab | Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0 last) | up to 99 days | 
| Assess Pharmacokinetic parameters of LY-CovMab | Percentage of the extrapolated area under the concentration-time curve (AUC_%Extrap) | up to 99 days | 
| Assess Pharmacokinetic parameters of LY-CovMab | Area under the concentration-time curve from time 0 to infinity (AUC0-inf), | up to 99 days | 
| Assess Pharmacokinetic parameters of LY-CovMab | Clearance (CL) | up to 99 days | 
| Assess Pharmacokinetic parameters of LY-CovMab | Half-life (t1/2) | up to 99 days | 
| Assess Pharmacokinetic parameters of LY-CovMab | Volume of distribution (Vd) | up to 99 days | 
| Assess the immunogenicity of LY-CovMab | Incidence of anti-drug antibody (ADA) | D1, D15, D29, D43, D57, D71, D99 | 
| Assess the immunogenicity of LY-CovMab | Incidence of neutralizing antibody (Nab) | D1, D15, D29, D43, D57, D71, D99 |