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

Phase 1

Completed

Conditions: Healthy Participants

Interventions: Drug: Placebo
Drug: XTMAB-16 2 mg/kg
Drug: XTMAB-16 4mg/kg

Registration Number: NCT04971395

Lead Sponsor: Xentria, Inc.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Single IV Infusion
XTMAB-16 2mg/kg	XTMAB-16 2 mg/kg	Single IV Infusion
XTMAB-16 4mg/kg	XTMAB-16 4mg/kg	Single IV Infusion

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
XTMAB-16 Maximum Observed Concentration (Cmax)	Up to day 71	XTMAB-16 (Cmax)
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
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 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-∞
Systemic Clearance After IV Dosing (CL)	Up to day 71	Systemic clearance after IV dosing (CL)
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
Apparent Terminal Half-life (t1/2)	Up to day 71