Covid19
Conditions
Brief summary
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
Interventions
DRUGBGB DXP593
Administered intravenously (IV) as specified in the treatment arm
DRUGPlacebo
Placebo to match BGB-DXP593
Sponsors
BeiGene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the day of study drug administration until 30 days after dose (up to approximately 160 days) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Relevant Changes in Laboratory Parameters | Up to approximately 160 days | Clinical laboratory values were evaluated for each laboratory parameter as applicable including hematology, serum chemistry and urinalysis. |
| 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 | — |
| Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms | Up to approximately 160 days | 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 |
| 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 | — |
| 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) | — |
Countries
Australia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single intravenous dose of matching placebo | 4 |
| BGB-DXP593 10 mg/kg Participants received a single 10 mg/kg intravenous dose of BGB-DXP593 | 6 |
| BGB-DXP593 30 mg/kg Participants received a single 30 mg/kg intravenous dose of BGB-DXP593 | 6 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Participants Not Dosed | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | BGB-DXP593 10 mg/kg | BGB-DXP593 30 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 31.0 years STANDARD_DEVIATION 13.64 | 34.2 years STANDARD_DEVIATION 16.46 | 39.7 years STANDARD_DEVIATION 14.81 | 35.4 years STANDARD_DEVIATION 14.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 5 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 4 | 4 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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
Time frame: From the day of study drug administration until 30 days after dose (up to approximately 160 days)
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with at least 1 TEAE | 4 Participants |
| Placebo | Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| BGB-DXP593 10 mg/kg | Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with at least 1 TEAE | 4 Participants |
| BGB-DXP593 10 mg/kg | Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
| BGB-DXP593 30 mg/kg | Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with at least 1 TEAE | 4 Participants |
| BGB-DXP593 30 mg/kg | Number of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Participants with SAEs | 0 Participants |
Secondary
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of BGB-DXP593
Time frame: 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)
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of BGB-DXP593 | 4168.8 day*μg/mL |
| BGB-DXP593 10 mg/kg | Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of BGB-DXP593 | 12422.6 day*μg/mL |
Secondary
AUC From Time Zero to Day 29 (AUC0-29) of BGB-DXP593
Time frame: Day 1 (pre-dose, End of Infusion, 6 hrs. post-dose), Days 2, 3, 4, 5, 8, 15, 22, and 29
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | AUC From Time Zero to Day 29 (AUC0-29) of BGB-DXP593 | 2368.4 day*μg/mL |
| BGB-DXP593 10 mg/kg | AUC From Time Zero to Day 29 (AUC0-29) of BGB-DXP593 | 6683.9 day*μg/mL |
Secondary
AUC From Time Zero to Time of Last Quantifiable Concentration (AUClast) of BGB-DXP593
Time frame: 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)
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | AUC From Time Zero to Time of Last Quantifiable Concentration (AUClast) of BGB-DXP593 | 3964.6 day*μg/mL |
| BGB-DXP593 10 mg/kg | AUC From Time Zero to Time of Last Quantifiable Concentration (AUClast) of BGB-DXP593 | 11434.2 day*μg/mL |
Secondary
Clearance (CL) of BGB-DXP593
Time frame: 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)
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Clearance (CL) of BGB-DXP593 | 0.18 Liters/Day |
| BGB-DXP593 10 mg/kg | Clearance (CL) of BGB-DXP593 | 0.19 Liters/Day |
Secondary
Immunogenic Response to BGB-DXP593 as Assessed by the Detection of Antidrug Antibodies (ADA)
Time frame: Up to approximately160 days
Population: The ADA Analysis Set includes all the participants who received the study drug and in whom both baseline ADA and at least 1 postbaseline ADA results are available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Immunogenic Response to BGB-DXP593 as Assessed by the Detection of Antidrug Antibodies (ADA) | Treatment Induced ADA | 1 Participants |
| Placebo | Immunogenic Response to BGB-DXP593 as Assessed by the Detection of Antidrug Antibodies (ADA) | Neutralizing antibody (NAb) Positive | 0 Participants |
| BGB-DXP593 10 mg/kg | Immunogenic Response to BGB-DXP593 as Assessed by the Detection of Antidrug Antibodies (ADA) | Treatment Induced ADA | 0 Participants |
| BGB-DXP593 10 mg/kg | Immunogenic Response to BGB-DXP593 as Assessed by the Detection of Antidrug Antibodies (ADA) | Neutralizing antibody (NAb) Positive | 0 Participants |
Secondary
Maximum Observed Plasma Concentration (Cmax) of BGB-DXP593
Time frame: 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)
Population: Pharmacokinetic (PK) Analysis Set includes all the participants who received the study drug and had any measurable concentration of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) of BGB-DXP593 | 255.3 μg/mL |
| BGB-DXP593 10 mg/kg | Maximum Observed Plasma Concentration (Cmax) of BGB-DXP593 | 667.0 μg/mL |
Secondary
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.
Time frame: Up to approximately 160 days
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Relevant Changes in Laboratory Parameters | 0 Participants |
| BGB-DXP593 10 mg/kg | Number of Participants With Clinically Relevant Changes in Laboratory Parameters | 0 Participants |
| BGB-DXP593 30 mg/kg | Number of Participants With Clinically Relevant Changes in Laboratory Parameters | 0 Participants |
Secondary
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
Time frame: Up to approximately 160 days
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms | Participants with changes in ECG | 0 Participants |
| Placebo | Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms | Participants with changes in vital signs | 0 Participants |
| BGB-DXP593 10 mg/kg | Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms | Participants with changes in vital signs | 0 Participants |
| BGB-DXP593 10 mg/kg | Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms | Participants with changes in ECG | 0 Participants |
| BGB-DXP593 30 mg/kg | Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms | Participants with changes in vital signs | 0 Participants |
| BGB-DXP593 30 mg/kg | Number of Participants With Clinically Relevant Changes in Vital Signs and Electrocardiograms | Participants with changes in ECG | 0 Participants |
Secondary
Terminal Half Life (t1/2) of BGB-DXP593
Time frame: 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)
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Terminal Half Life (t1/2) of BGB-DXP593 | 26.60 Day |
| BGB-DXP593 10 mg/kg | Terminal Half Life (t1/2) of BGB-DXP593 | 25.77 Day |
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of BGB-DXP593
Time frame: 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)
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Maximum Observed Plasma Concentration (Tmax) of BGB-DXP593 | 1.47 hours |
| BGB-DXP593 10 mg/kg | Time to Maximum Observed Plasma Concentration (Tmax) of BGB-DXP593 | 3.67 hours |
Secondary
Volume of Distribution (Vz) of BGB-DXP593
Time frame: 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)
Population: PK Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Volume of Distribution (Vz) of BGB-DXP593 | 6.54 Liters |
| BGB-DXP593 10 mg/kg | Volume of Distribution (Vz) of BGB-DXP593 | 6.30 Liters |