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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19
• Intervention / Treatment: Drug: LY-CovMab

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Luye Pharma Group Ltd.
• Collaborators: Shandong Boan Biotechnology Co., Ltd
• Investigators: Principal Investigator: Hui Zhao, Dr, The Second Hospital of Anhui Medical University; Principal Investigator: Wei Hu, Dr, The Second Hospital of Anhui Medical University

Publications and helpful links

General Publications

• Zhang Q, Zhou R, Yang J, Dou C, Gan T, Liu F, Hu B, Song D, Lu C, Hu W. A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2. Infect Dis Ther. 2022 Feb;11(1):405-422. doi: 10.1007/s40121-021-00572-x. Epub 2021 Dec 8.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Actual): May 1, 2021
• Study Completion (Anticipated): July 31, 2021

Study Registration Dates

• First Submitted: June 30, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: LY-CovMab/CT-CHN-101

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