This is a first-in-human, two-part, Phase 1 study that will characterize the safety, tolerability, PK, and immunogenicity of HuL001.
This is a first-in-human, two-part, Phase 1 study that will characterize the safety, tolerability, PK, and immunogenicity of HuL001 after single ascending doses in healthy subjects followed by multiple doses in IPF subjects. The study will be conducted in 2 parts: * Part A will enroll 3 single ascending doses (SAD) cohorts in healthy subjects. (HuL001:Placebo=4:2) * Part B will enroll 1 multiple-dose cohort in IPF subjects. The proposed dose of HuL001 will be selected from the single-dose range of HuL001 evaluated in the healthy subjects of Part A. (HuL001=6)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
24
Anti-ENO1 monoclonal antibody
Mackay Memorial Hospital
New Taipei City, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Frequency, severity, and causality of adverse events (AEs), including solicited local AEs
Frequency, severity, and causality of adverse events (AEs), including solicited local AEs
Time frame: 70 Days in Part A and 84 Days in Part B
Proportion of subjects who report clinically significant abnormal findings in physical examination
Proportion of subjects who report clinically significant abnormal findings in physical examination
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in blood pressure
Change from baseline in systolic and diastolic blood pressure
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in respiratory rate
Change from baseline in respiratory rate
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in heart rate
Change from baseline in heart rate
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in body temperature
Change from baseline in body temperature
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in hematology assessments
The hematology assessments including hematocrit, hemoglobin, platelet count, red blood cell (RBC) count, white blood cell (WBC) count (total and differential), reticulocyte count and absolute neutrophil count.
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in biochemistry assessments
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The biochemistry assessments including alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), amylase, aspartate aminotransferase (AST), bicarbonate, blood urea nitrogen (BUN), calcium, chloride, creatinine, creatinine kinase, gamma glutamyl transferase (GGT), glucose, lactic acid dehydrogenase (LDH), lipid panel (low and high density lipids cholesterol, triglycerides; total cholesterol), magnesium, potassium, sodium, total bilirubin, total protein and uric acid.
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in electrocardiogram (ECG) results (including PR, QRS, QT, QTcF, and RR intervals)
Change from baseline in electrocardiogram (ECG) results
Time frame: 70 Days in Part A and 84 Days in Part B
Tolerability of HuL001 in terms of frequency of events meeting the intra-cohort stopping criteria within the tolerability observation period
Tolerability of HuL001 in terms of frequency of events meeting the intra-cohort stopping criteria within the tolerability observation period
Time frame: 70 Days in Part A and 84 Days in Part B
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- maximum observed concentration (Cmax)
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- maximum observed concentration (Cmax)
Time frame: 70 Days in Part A and 84 Days in Part B
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects-time to reach Cmax (tmax)
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects-time to reach Cmax (tmax)
Time frame: 70 Days in Part A and 84 Days in Part B
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- area under the curve from zero up to time t (AUC0-t)
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- area under the curve from zero up to time t (AUC0-t)
Time frame: 70 Days in Part A and 84 Days in Part B
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- apparent total clearance of the drug from plasma (CL/F)
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- apparent total clearance of the drug from plasma (CL/F)
Time frame: 70 Days in Part A and 84 Days in Part B
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- terminal half-life (t1/2)
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- terminal half-life (t1/2)
Time frame: 70 Days in Part A and 84 Days in Part B
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- apparent volume of distribution during terminal phase (Vz/F)
PK of single ascending doses of HuL001 in healthy subjects and multiple doses of HuL001 in IPF subjects- apparent volume of distribution during terminal phase (Vz/F)
Time frame: 70 Days in Part A and 84 Days in Part B
Proportion of subjects with positive anti-HuL001 antibodies
Proportion of subjects with positive anti-HuL001 antibodies
Time frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in serum levels of cytokines
Change from baseline in serum levels of cytokines
Time frame: 70 Days in Part A and 84 Days in Part B