Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Infusion of XTMAB-16 in Healthy Adult Participants

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-blind, Placebo Controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Infusion of XTMAB-16 in Healthy Adult Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: XTMAB-16 2mg/kg
* Drug: Placebo
* Drug: XTMAB-16 4mg/kg


Participation Criteria
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Eligibility Criteria
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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.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single IV infusion of 2 mg/kg of XTMAB-16 or placebo<br>Sentinel group: Each cohort will have a sentinel group of 2 participants (1:1 XTMAB-16 and placebo, respectively). dosed at least 48 hours before the remaining participants in the same cohort. (Up to 99 days) After safety is confirmed, the remaining patients within the same cohort will be dosed. Remaining group: Each cohort will then enroll 10 participants (8:2 XTMAB-16 and placebo, respectively) (Up to 99 days) | Drug: XTMAB-16 2mg/kg<br>* Biological XTMAB-16 IV infusion single dose<br>Drug: Placebo<br>* Placebo; IV infusion single dose<br>|
| Experimental: Single IV infusion of 4 mg/kg of XTMAB-16 or placebo<br>Sentinel group: Each cohort will have a sentinel group of 2 participants (1:1 XTMAB-16 and placebo, respectively). dosed at least 48 hours before the remaining participants in the same cohort. (Up to 99 days) After safety is confirmed, the remaining patients within the same cohort will be dosed. Remaining group: Each cohort will then enroll 10 participants (8:2 XTMAB-16 and placebo, respectively) (Up to 99 days) | Drug: Placebo<br>* Placebo; IV infusion single dose<br>Drug: XTMAB-16 4mg/kg<br>* Biological XTMAB-16 IV infusion single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Safety and Tolerability] |  | Up to day 71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of participants by cohort who test positive for XTMAB-16 ADA |  | Up to day 71 | 
| Incidence of participants by cohort who test positive for XTMAB-16 nAb |  | Up to day 71 | 
| Maximum observed XTMAB-16 concentration (Cmax) |  | Up to day 71 | 
| XTMAB-16 serum concentration at the end of drug infusion (CT) |  | Up to day 71 | 
| Time to maximum observed XTMAB-16 concentration (tmax) |  | Up to day 71 | 
| Area under the XTMAB-16 concentration-time curve from time zero (predose) extrapolated to infinity (AUC0-∞) |  | Up to day 71 | 
| Area under the XTMAB-16 concentration-time-curve from time zero to (predose) to the last quantifiable time point at t (AUC0-t) |  | Up to day 71 | 
| Systemic clearance after IV dosing (CL) |  | Up to day 71 | 
| Apparent terminal half-life (t1/2) |  | Up to day 71 | 
| Volume of distribution following IV dosing (Vz) |  | Up to day 71 | 
| Mean residence time (MRT) |  | Up to day 71 |