Healthy Participants
Conditions
Brief summary
This is a single-center, randomized, double-blind, placebo-controlled, first-in-human, single intravenous (IV) infusion of XTMAB-16 (formerly referred to as KBMAB-16) in normal healthy male and female participants.
Detailed description
A total of 24 normal healthy adult participants will be enrolled and assigned into 2 treatment cohorts with 12 participants (9 on XTMAB-16 and 3 on placebo) in each cohort. Participants will receive a single IV infusion of 2 mg/kg or 4 mg/kg of XTMAB-16 or placebo on Day 1.
Interventions
DRUGPlacebo
Single dose of 2 or 4 mg/kg
DRUGXTMAB-16 2 mg/kg
Single dose of 2 mg/kg
DRUGXTMAB-16 4mg/kg
Single dose of 4 mg/kg
Sponsors
Xentria, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * The participant is a healthy adult male or female aged 18 to 45 years, inclusive, at the time of informed consent. * The participant weighs between 45 kg (99 lbs) and 100 kg (220 lbs) and has a body mass index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at the time of informed consent. * The participant agrees to use highly effective method of contraception from the time of signing consent throughout 90 days after dosing. Key
Exclusion criteria
* The participant has received any investigational compound within 90 days before dosing. * The participant has any clinically significant illness, such as cardiovascular, neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine, or psychiatric disease or disorder, or other abnormality, which may affect the participant's safety, increase risk of seizure or lower the seizure threshold, or potentially confound the study results. It is the responsibility of the Investigator to assess the clinical significance of any conditions the participant may have; however, consultation with the Xentria Medical Monitor may be warranted. * The participant has a known hypersensitivity to any component of the formulation of XTMAB-16. * The participant has a positive result for drugs of abuse (defined as any illicit drug use) or alcohol at Screening or Baseline (Day -2). * The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to Screening or is unwilling to agree to abstain from alcohol and drugs throughout the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant With Treatment Emergent Adverse Events (TEAEs) | Up to day 71 | Treatment-emergent adverse event, which is an undesirable event that occurs during or shortly after treatment begins. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | ADA and nAB: Days 1, 8, 15, 29, 43, 57, 71 | Participants by cohort who test positive for XTMAB-16 nAb |
| XTMAB-16 Maximum Observed Concentration (Cmax) | Up to day 71 | XTMAB-16 (Cmax) |
| XTMAB-16 Serum Observed Plasma Concentration at the End of Infusion (CT) Day 1 | Day 1 | XTMAB-16 serum (CT) Day 1 |
| Time to Maximum Observed Concentration (Tmax) XTMAB-16 | PK: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71 | Time to maximum observed concentration (tmax) XTMAB-16 |
| Area Under the XTMAB-16 Concentration-time Curve From Time Zero (Predose) Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) | PK: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71 | Area under the XTMAB-16 concentration-time curve from time zero (predose) AUC0-∞ |
| Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | ADA and nAB: Days 1, 8, 15, 29, 43, 57, 71 | Participants by cohort who test positive for XTMAB-16 ADA |
| Systemic Clearance After IV Dosing (CL) | Up to day 71 | Systemic clearance after IV dosing (CL) |
| Apparent Terminal Half-life (t1/2) | Up to day 71 | — |
| Volume of Distribution Following IV Dosing (Vz) Day 1 up to Day 71 | Up to day 71 | — |
| Mean Residence Time (MRT) | Up to day 71 | Mean residence time (MRT) |
| Area Under the XTMAB-16 Concentration-time-curve From Time Zero to (Predose) Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) | PK: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71 | Area under the XTMAB-16 concentration-time-curve from time zero to (predose) AUC0-t |
Countries
United States
Participant flow
Pre-assignment details
A total of 24 normal healthy adult participants were planned to be enrolled and assigned into 2 treatment cohorts with 12 participants (9 on XTMAB-16 and 3 on placebo). Participants received a single IV infusion of 2 or 4 mg/kg of study drug (XTMAB-16 or placebo) on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Single IV Infusion of 2 mg/kg of XTMAB-16 Participants received a single dose of 2 mg/kg XTMAB-16 | 10 |
| Single IV Infusion of 4 mg/kg of XTMAB-16 Participants received a single dose of 4 mg/kg XTMAB-16 | 9 |
| Pooled Placebo Participants received a single IV Infusion of Placebo | 6 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Single IV Infusion of 2 mg/kg of XTMAB-16 | Single IV Infusion of 4 mg/kg of XTMAB-16 | Pooled Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 6 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 7 Participants | 4 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 8 Participants | 4 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 3 Participants | 16 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 3 / 10 | 4 / 9 | 2 / 6 |
| serious Total, serious adverse events | 0 / 10 | 1 / 9 | 0 / 6 |
Outcome results
Primary
Participant With Treatment Emergent Adverse Events (TEAEs)
Treatment-emergent adverse event, which is an undesirable event that occurs during or shortly after treatment begins.
Time frame: Up to day 71
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2 mg/kg XTMAB-16 | Participant With Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
| 4 mg/kg XTMAB-16 | Participant With Treatment Emergent Adverse Events (TEAEs) | 3 Participants |
| Pooled Placebo | Participant With Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
Secondary
Apparent Terminal Half-life (t1/2)
Time frame: Up to day 71
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Apparent Terminal Half-life (t1/2) | 8.644 t1/2 (day) | Standard Deviation 4.726 |
| 4 mg/kg XTMAB-16 | Apparent Terminal Half-life (t1/2) | 10.23 t1/2 (day) | Standard Deviation 3.617 |
Secondary
Area Under the XTMAB-16 Concentration-time Curve From Time Zero (Predose) Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞)
Area under the XTMAB-16 concentration-time curve from time zero (predose) AUC0-∞
Time frame: PK: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Area Under the XTMAB-16 Concentration-time Curve From Time Zero (Predose) Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) | 601.5 AUC0-inf (day*μg/mL) | Standard Deviation 231.8 |
| 4 mg/kg XTMAB-16 | Area Under the XTMAB-16 Concentration-time Curve From Time Zero (Predose) Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) | 1249 AUC0-inf (day*μg/mL) | Standard Deviation 245 |
Secondary
Area Under the XTMAB-16 Concentration-time-curve From Time Zero to (Predose) Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t)
Area under the XTMAB-16 concentration-time-curve from time zero to (predose) AUC0-t
Time frame: PK: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Area Under the XTMAB-16 Concentration-time-curve From Time Zero to (Predose) Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) | 525.2 AUC0-last (day*μg/mL) | Standard Deviation 238 |
| 4 mg/kg XTMAB-16 | Area Under the XTMAB-16 Concentration-time-curve From Time Zero to (Predose) Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) | 1224 AUC0-last (day*μg/mL) | Standard Deviation 235.9 |
Secondary
Mean Residence Time (MRT)
Mean residence time (MRT)
Time frame: Up to day 71
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Mean Residence Time (MRT) | 12.51 MRT (day) | Standard Deviation 6.214 |
| 4 mg/kg XTMAB-16 | Mean Residence Time (MRT) | 13.32 MRT (day) | Standard Deviation 3.794 |
Secondary
Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA)
Participants by cohort who test positive for XTMAB-16 ADA
Time frame: ADA and nAB: Days 1, 8, 15, 29, 43, 57, 71
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 29 ADA Confirmatory | 1 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 8 ADA Screening | 0 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 57 ADA Screening | 6 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 29 ADA Screening | 1 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 15 ADA Screening | 1 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 71 ADA Confirmatory | 6 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 15 ADA Confirmatory | 0 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 71 ADA Screening | 6 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 43 ADA Confirmatory | 3 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 43 ADA Screening | 4 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 1 ADA Screening | 0 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 57 ADA Confirmatory | 5 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 57 ADA Screening | 1 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 57 ADA Confirmatory | 1 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 71 ADA Screening | 3 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 71 ADA Confirmatory | 2 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 1 ADA Screening | 0 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 8 ADA Screening | 0 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 15 ADA Screening | 1 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 15 ADA Confirmatory | 0 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 29 ADA Screening | 0 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 29 ADA Confirmatory | 0 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 43 ADA Screening | 0 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 43 ADA Confirmatory | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 29 ADA Screening | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 1 ADA Screening | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 43 ADA Confirmatory | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 29 ADA Confirmatory | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 57 ADA Screening | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 71 ADA Screening | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 43 ADA Screening | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 15 ADA Screening | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 71 ADA Confirmatory | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 15 ADA Confirmatory | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 8 ADA Screening | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Anti-drug Antibody (ADA) | Day 57 ADA Confirmatory | 0 Participants |
Secondary
Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb)
Participants by cohort who test positive for XTMAB-16 nAb
Time frame: ADA and nAB: Days 1, 8, 15, 29, 43, 57, 71
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 29 | 1 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 43 | 3 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 57 | 5 Participants |
| 2 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 71 | 6 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 71 | 2 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 29 | 0 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 57 | 1 Participants |
| 4 mg/kg XTMAB-16 | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 43 | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 71 | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 43 | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 57 | 0 Participants |
| Pooled Placebo | Participants by Cohort Who Test Positive for XTMAB-16 Neutralizing Antibody (nAb) | Day 29 | 0 Participants |
Secondary
Systemic Clearance After IV Dosing (CL)
Systemic clearance after IV dosing (CL)
Time frame: Up to day 71
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Systemic Clearance After IV Dosing (CL) | 0.2498 CL (L/day) | Standard Deviation 0.04883 |
| 4 mg/kg XTMAB-16 | Systemic Clearance After IV Dosing (CL) | 0.2449 CL (L/day) | Standard Deviation 0.06064 |
Secondary
Time to Maximum Observed Concentration (Tmax) XTMAB-16
Time to maximum observed concentration (tmax) XTMAB-16
Time frame: PK: Days 1, 2, 3, 4, 8, 15, 29, 43, 57, 71
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2 mg/kg XTMAB-16 | Time to Maximum Observed Concentration (Tmax) XTMAB-16 | 2.16 tmax (h) |
| 4 mg/kg XTMAB-16 | Time to Maximum Observed Concentration (Tmax) XTMAB-16 | 3.0 tmax (h) |
Secondary
Volume of Distribution Following IV Dosing (Vz) Day 1 up to Day 71
Time frame: Up to day 71
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | Volume of Distribution Following IV Dosing (Vz) Day 1 up to Day 71 | 2.864 Vz (L) | Standard Deviation 0.8861 |
| 4 mg/kg XTMAB-16 | Volume of Distribution Following IV Dosing (Vz) Day 1 up to Day 71 | 3.435 Vz (L) | Standard Deviation 0.9878 |
Secondary
XTMAB-16 Maximum Observed Concentration (Cmax)
XTMAB-16 (Cmax)
Time frame: Up to day 71
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | XTMAB-16 Maximum Observed Concentration (Cmax) | 64.17 Cmax (μg/mL) | Standard Deviation 9.94 |
| 4 mg/kg XTMAB-16 | XTMAB-16 Maximum Observed Concentration (Cmax) | 131 Cmax (μg/mL) | Standard Deviation 23.42 |
Secondary
XTMAB-16 Serum Observed Plasma Concentration at the End of Infusion (CT) Day 1
XTMAB-16 serum (CT) Day 1
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 mg/kg XTMAB-16 | XTMAB-16 Serum Observed Plasma Concentration at the End of Infusion (CT) Day 1 | 62.18 CT (μg/mL) | Standard Deviation 6.757 |
| 4 mg/kg XTMAB-16 | XTMAB-16 Serum Observed Plasma Concentration at the End of Infusion (CT) Day 1 | 128.9 CT (μg/mL) | Standard Deviation 22.39 |