A Phase 1 Single and Multiple Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Immunogenicity of HuL001 in Healthy Volunteers and Idiopathic Pulmonary Fibrosis Subjects
Overview
- Phase
- Phase 1
- Intervention
- HuL001
- Conditions
- Idiopathic Pulmonary Fibrosis
- Sponsor
- HuniLife Biotechnology, Inc.
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Change from baseline in respiratory rate
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a first-in-human, two-part, Phase 1 study that will characterize the safety, tolerability, PK, and immunogenicity of HuL001.
Detailed Description
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)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who meet the following criteria will be eligible to participate in the study:
- •Healthy and IPF Subjects
- •Female subjects and male subjects with female partners of child-bearing potential must agree to use adequate contraception (2 forms of birth control, one of which must be a barrier method). This criterion must be followed from the time of the first dose of treatment.
- •Able to understand, sign the written informed consent form, and follow the study procedures.
- •With no clinically significant abnormalities in vital signs, 12-lead ECG, and clinical laboratory assessments at screening as judged by the Investigator
- •Corrected QT interval using Fridericia's (QTcF) \< 450 milliseconds (msec).
- •Healthy Subjects only
- •Aged between 20 and 55 years of age inclusive, at the time of signing the informed consent.
- •Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and bilirubin ≤ 1.5x upper limit of normal (ULN) (isolated bilirubin \> 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%).
- •Body weight ≥ 50 kilogram (kg), \< 75 kg and body mass index (BMI) within the range 19.0 - 29.9 kg/m2 (inclusive).
Exclusion Criteria
- •Subjects presenting with any of the following criteria will be excluded from participating in the study:
- •Healthy and IPF Subjects
- •Female subjects who are breastfeeding, pregnant, or planning to become pregnant during the study period.
- •The Investigator considers that the subject is not in the condition to participate in this study.
- •Evidence or history of clinically significant (as judged by the Investigator) hematologic, renal, endocrine, pulmonary (except for IPF subjects), gastrointestinal, cardiovascular (except for IPF subjects), hepatic, psychiatric, immunologic, metabolic, urologic, dermatologic, neurologic or allergic diseases, or other significant clinical findings within 3 months prior to screening.
- •Has participated in a clinical trial and has received an investigational product (IP) within 60 days prior to screening.
- •Previous history of anaphylaxis and severe allergic reaction, generation of neutralizing antibodies, or hypersensitivity to albumin or a protein-based therapeutic, or any other monoclonal antibody.
- •Had blood donation within 60 days or had blood donation over 250 mL within 90 days prior to screening, or cannot commit to stopping blood donation during the study period.
- •Receipt of vaccination within 1 month of screening or plan to receive vaccination during the study.
- •Have significant active infection (acute or chronic) within 28 days prior to screening.
Arms & Interventions
Part A 1 (1 mg/kg HuL001)
6 healthy subjects will be enrolled and randomized to receive 1 dose of HuL001 (n = 4) or 1 dose of placebo (n = 2).
Intervention: HuL001
Part A 2 (3 mg/kg HuL001)
6 healthy subjects will be enrolled and randomized to receive 1 dose of HuL001 (n = 4) or 1 dose of placebo (n = 2).
Intervention: HuL001
Part A 3 (5 mg/kg HuL001)
6 healthy subjects will be enrolled and randomized to receive 1 dose of HuL001 (n = 4) or 1 dose of placebo (n = 2).
Intervention: HuL001
Part B 1 (Selected Dose)
At the end of Part A, the SRC will review the accumulated unblinded data of safety, tolerability, PK (any available data), and immunogenicity (any available data) to select a dose to initiate Part B in IPF subjects. Part B will be conducted in multiple-dose, uncontrolled, and open-label manner to explore the safety, tolerability, PK, and immunogenicity in IPF subjects. Only one cohort will be enrolled to receive 3 repeated doses of the selected HuL001 dose, which will be administered bi-weekly. A total of 6 IPF subjects will be enrolled in this multiple-dose cohort.
Intervention: HuL001
Outcomes
Primary Outcomes
Change from baseline in respiratory rate
Time Frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in respiratory rate
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
Tolerability of HuL001 in terms of frequency of events meeting the intra-cohort stopping criteria within the tolerability observation period
Change from baseline in blood pressure
Time Frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in systolic and diastolic blood pressure
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
Proportion of subjects who report clinically significant abnormal findings in physical examination
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
Frequency, severity, and causality of adverse events (AEs), including solicited local AEs
Change from baseline in heart rate
Time Frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in heart rate
Change from baseline in electrocardiogram (ECG) results (including PR, QRS, QT, QTcF, and RR intervals)
Time Frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in electrocardiogram (ECG) results
Change from baseline in body temperature
Time Frame: 70 Days in Part A and 84 Days in Part B
Change from baseline in body temperature
Change from baseline in hematology assessments
Time Frame: 70 Days in Part A and 84 Days in Part B
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.
Change from baseline in biochemistry assessments
Time Frame: 70 Days in Part A and 84 Days in Part B
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.
Secondary Outcomes
- Proportion of subjects with positive anti-HuL001 antibodies(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)(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)(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)(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)(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)(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)(70 Days in Part A and 84 Days in Part B)
- Change from baseline in serum levels of cytokines(70 Days in Part A and 84 Days in Part B)