This is a Phase I, single-center, double-blind, placebo-controlled dose escalation trial of three dose cohorts (A: 0.033 mg/kg, B: 0.165 mg/kg, and C: 0.33 mg/kg). The purpose of this study is to evaluate the safety and tolerability of NTM-1633 in healthy adults. This is a first-in-human study consisting of three cohorts of eight subjects each. Dosing for each cohort is as follows: Two sentinel subjects will be administered a single 1-hour infusion (one NTM-1633, one placebo). No more than two subjects per day thereafter (at least 24 hrs will elapse between the dosing of each two subjects) will be dosed in the same manner until all subjects are dosed. Dose escalation will not occur until safety data through Day 8 is reviewed by the Safety Review Committee (SRC). Objective dose-escalation criteria and safety evaluations will be utilized. The study duration will be for approximately 8 months. Subjects in Cohort A will participate for approximately 17 weeks and Subjects in Cohorts B and C will participate approximately 21 weeks. Primary Objective: To assess the safety and tolerability of escalating doses of NTM-1633 administered intravenously in healthy adults.
This is a Phase I, single-center, double-blind, placebo-controlled dose escalation trial of three dose cohorts (A: 0.033 mg/kg, B: 0.165 mg/kg, and C: 0.33 mg/kg). The purpose of this study is to evaluate the safety and tolerability of NTM-1633 in healthy adults. This is a first-in-human study consisting of three cohorts of eight subjects each. Dosing for each cohort is as follows: Two sentinel subjects will be administered a single 1-hour infusion (one NTM-1633, one placebo). No more than two subjects per day thereafter (at least 24 hrs will elapse between the dosing of each two subjects) will be dosed in the same manner until all subjects are dosed. Dose escalation will not occur until safety data through Day 8 is reviewed by the Safety Review Committee (SRC). Objective dose-escalation criteria and safety evaluations will be utilized. The study duration will be for approximately 8 months. Subjects in Cohort A will participate for approximately 17 weeks and Subjects in Cohorts B and C will participate approximately 21 weeks. Primary Objective: To assess the safety and tolerability of escalating doses of NTM-1633 administered intravenously in healthy adults. Secondary Objectives: 1) To assess the pharmacokinetic characteristics of NTM-1633 following a single intravenous administration; 2) To assess the immunogenicity of NTM-1633 following a single intravenous administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
NTM-1633 is an equimolar mixture of three IgG1 monoclonal antibodies (mAb), referred to as XE02, XE06, and XE17 which bind to non-overlapping epitopes on Botulinum Neurotoxin (BoNT/E). Administered as a single intravenous infusion of NTM-1633 over one hour.
0.9% Sodium Chloride Injection administered as a single intravenous infusion over one hour.
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
Durham, North Carolina, United States
The occurrence of AEs
Time frame: From Day 1 through Day 57
The occurrence of changes in absolute neutrophil count
Time frame: From Day -1 through Day 91
The occurrence of changes in alanine transaminase (ALT) level
Time frame: From Day -1 through Day 91
The occurrence of changes in aldolase level
Time frame: From Day -1 through Day 91
The occurrence of changes in alkaline phosphatase level
Time frame: From Day -1 through Day 91
The occurrence of changes in aspartate transaminase (AST) level
Time frame: From Day -1 through Day 91
The occurrence of changes in blood urea nitrogen (BUN) level
Time frame: From Day -1 through Day 91
The occurrence of changes in calcium level
Time frame: From Day -1 through Day 91
The occurrence of changes in Complete Blood Count (CBC) with differential
Time frame: From Day -1 through Day 91
The occurrence of changes in diastolic blood pressure in arm A
Time frame: From Day -1 through Day 91
The occurrence of changes in diastolic blood pressure in arms B and C
Time frame: From Day -1 through Day 121
The occurrence of changes in direct bilirubin level
Time frame: From Day -1 through Day 91
The occurrence of changes in heart rate in arm A
Time frame: From Day -1 through Day 91
The occurrence of changes in heart rate in arms B and C
Time frame: From Day -1 through Day 121
The occurrence of changes in hemoglobin level
Time frame: From Day -1 through Day 91
The occurrence of changes in indirect bilirubin level
Time frame: From Day -1 through Day 91
The occurrence of changes in oral temperature in arm A
Time frame: From Day -1 through Day 91
The occurrence of changes in oral temperature in arms B and C
Time frame: From Day -1 through Day 121
The occurrence of changes in physical examination in arm A
Time frame: From Day -1 through Day 91
The occurrence of changes in physical examination in arms B and C
Time frame: From Day -1 through Day 121
The occurrence of changes in platelet count
Time frame: From Day -1 through Day 91
The occurrence of changes in potassium level
Time frame: From Day -1 through Day 91
The occurrence of changes in prothrombin time/international normalized ratio (INR)
Time frame: From Day -1 through Day 91
The occurrence of changes in serum creatinine level
Time frame: From Day -1 through Day 91
The occurrence of changes in sodium level
Time frame: From Day -1 through Day 91
The occurrence of changes in systolic blood pressure in arm A
Time frame: From Day -1 through Day 91
The occurrence of changes in systolic blood pressure in arms B and C
Time frame: From Day -1 through Day 121
The occurrence of changes in total bilirubin level
Time frame: From Day -1 through Day 91
The occurrence of changes in total creatine kinase (CK) level
Time frame: From Day -1 through Day 91
The occurrence of changes in White Blood Cell (WBC) count
Time frame: From Day -1 through Day 91
The occurrence of clinically significant ECG abnormalities
Time frame: From Day -28 through Day 1
The occurrence of QT interval abnormalities
Time frame: From Day -28 through Day 1
The occurrence of SAEs in arm A
Time frame: From Day 1 through Day 91
The occurrence of SAEs in arms B and C
Time frame: From Day 1 through Day 121
The presence of protein, blood, or glucose in urine
Time frame: From Day -1 through Day 91
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE02 in arm A
Time frame: From Day 1 through Day 91
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE02 in arms B and C
Time frame: From Day 1 through Day 121
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE06 in arm A
Time frame: From Day 1 through Day 91
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE06 in arms B and C
Time frame: From Day 1 through Day 121
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE17 in arm A
Time frame: From Day 1 through Day 91
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE17 in arms B and C
Time frame: From Day 1 through Day 121
Maximum observed plasma concentration (Cmax) for XE02 in arm A
Time frame: From Day 1 through Day 91
Maximum observed plasma concentration (Cmax) for XE02 in arms B and C
Time frame: From Day 1 through Day 121
Maximum observed plasma concentration (Cmax) for XE06 in arm A
Time frame: From Day 1 through Day 91
Maximum observed plasma concentration (Cmax) for XE06 in arms B and C
Time frame: From Day 1 through Day 121
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Maximum observed plasma concentration (Cmax) for XE17 in arm A
Time frame: From Day 1 through Day 91
Maximum observed plasma concentration (Cmax) for XE17 in arms B and C
Time frame: From Day 1 through Day 121
The presence of human anti-human antibodies (HAHA)
Time frame: Day 1
The presence of human anti-human antibodies (HAHA)
Time frame: Day 29
The presence of human anti-human antibodies (HAHA)
Time frame: Day 57
The presence of human anti-human antibodies (HAHA)
Time frame: Day 91
The presence of human anti-human antibodies (HAHA) for Arms B and C
Time frame: Day 121
Time to maximum observed plasma concentration (Tmax) for XE02 in arm A
Time frame: From Day 1 through Day 91
Time to maximum observed plasma concentration (Tmax) for XE02 in arms B and C
Time frame: From Day 1 through Day 121
Time to maximum observed plasma concentration (Tmax) for XE06 in arm A
Time frame: From Day 1 through Day 91
Time to maximum observed plasma concentration (Tmax) for XE06 in arms B and C
Time frame: From Day 1 through Day 121
Time to maximum observed plasma concentration (Tmax) for XE17 in arm A
Time frame: From Day 1 through Day 91
Time to maximum observed plasma concentration (Tmax) for XE17 in arms B and C
Time frame: From Day 1 through Day 121