Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/COVID-19) Neutralizing Antibody in Healthy Participants

A First-in-Human, Randomized, Double-Blind, Placebo Controlled, Single Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Healthy Subjects

The primary purpose of this study is to investigate the safety and tolerability of BGB-DXP593 administered intravenously as a single dose in healthy participants

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: BGB DXP593; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Q PHARM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria :

1. Participants are in good general health as determined by the investigator or medically qualified designee, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring
2. Body weight ≥ 50 kg and body mass index (BMI) within the range 18 to 32 kg/m2 (inclusive) Note: BMI = weight [kg] / (height [m])
3. Negative serum IgG to the SARS-CoV-2
4. Negative for COVID-19 based on the nasopharyngeal or oropharyngeal swab with the method of real-time reverse transcription-polymerase chain reaction (rRT-PCR)

Key Exclusion Criteria:

1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, constituting a risk to the participant when taking the study drug; or interfering with the interpretation of data
2. Any history of a severe allergic reaction prior to enrollment that has a reasonable risk of recurrence during the study
3. Have a medical history of SARS infection
4. Any acute fever disease or infections
5. Any chronic or clinically significant medical condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant, including but not limited to: diabetes mellitus type I, chronic hepatitis; or clinically significant forms of: drug or alcohol abuse, asthma (except for childhood asthma), autoimmune disease, psychiatric disorders, or heart disease

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BGB-DXP593: Dose Level A; Participants will receive BGB-DXP593 10 mg/kg on Day 1	Drug: BGB DXP593; Administered intravenously (IV) as specified in the treatment arm
Experimental: BGB-DXP593: Dose Level B; Participants will receive BGB-DXP593 30 mg/kg on Day 1	Drug: BGB DXP593; Administered intravenously (IV) as specified in the treatment arm
Experimental: Placebo; Placebo to match (PTM) BGB-DXP593 on Day 1	Drug: Placebo; Placebo to match BGB-DXP593

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	A TEAE is defined as an adverse event (AE) that had an onset date or a worsening in severity from baseline on or after the administration of study drug and up to 30 days after the dose of study drug	From the day of study drug administration until 30 days after dose (up to approximately 160 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms	Systolic and diastolic blood pressure, pulse rate, body temperature, and respiratory rate were measured. Descriptive statistics for ECG parameters (heart rate and QTcF interval) and changes from baseline were summarized	Up to approximately 160 days
Number of Participants With Clinically Relevant Changes in Laboratory Parameters	Clinical laboratory values were evaluated for each laboratory parameter as applicable including hematology, serum chemistry and urinalysis.	Up to approximately 160 days
Maximum Observed Plasma Concentration (Cmax) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71, 85 and End of study visit (Up to approximately160 days)
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71, 85 and End of study visit (Up to approximately160 days)
AUC From Time Zero to Time of Last Quantifiable Concentration (AUClast) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71, 85 and End of study visit (Up to approximately160 days)
AUC From Time Zero to Day 29 (AUC0-29) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, and 29
Time to Maximum Observed Plasma Concentration (Tmax) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71, 85 and End of study visit (Up to approximately160 days)
Terminal Half Life (t1/2) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71, 85 and End of study visit (Up to approximately160 days)
Clearance (CL) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71, 85 and End of study visit (Up to approximately160 days)
Volume of Distribution (Vz) of BGB-DXP593		Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, 29, 43, 57, 71, 85 and End of study visit (Up to approximately160 days)
Immunogenic Response to BGB-DXP593 as Assessed by the Detection of Antidrug Antibodies (ADA)		Up to approximately160 days

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Study Director, BeiGene

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Actual): February 13, 2021
• Study Completion (Actual): February 13, 2021

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: BGB-DXP593-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No