Study of a Single Dose of PRS-060 Administered by Oral Inhalation or IV Infusion in Healthy Subjects

Study Overview
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Brief Summary
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A Dose Escalating Study of PRS-060 Administered by Oral Inhalation or IV Infusion in Healthy Subjects

Detailed Description
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PRS-060 is a new drug being developed for treatment of asthma. The main purpose of this study is to investigate the safety, tolerability and pharmacokinetics of single ascending doses of PRS-060 in healthy subjects

Official Title
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A Dose Escalating Single Blind Study to Assess the Safety, Tolerability and Pharmacokinetics of a Single Dose of PRS-060 Administered by Oral Inhalation or IV Infusion in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: PRS-060
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female of non-childbearing potential (post-menopausal or surgically sterilized) subjects of 18 to 55 years of age Body mass index (BMI) of 18-35 Subjects who are non-smokers or ex-smokers who have not smoked in the last 6 months (determined by urine cotinine < 500 ng/ml, at screening visit). Exclusion Criteria: History or clinical manifestations of any clinically significant medical disorder that, in the opinion of the investigator, may put the subject at risk because of participation in the study, influence the results of the study or affect the subject's ability to participate in the study. A history of drug or alcohol abuse. History of, or known significant infection including hepatitis A, B, or C, Human immunodeficiency Virus (HIV), tuberculosis (i.e., positive result for Interferon (INF)-y release assay (IGRA), QuantiFERON TB-Gold), that may put the subject at risk during participation in the study. Any clinically significant illness, infection, medical/surgical procedure, or trauma within 4 weeks of day 1 or planned inpatient surgery or hospitalization during the study period. Subjects with any history of malignancy or neoplastic disease. Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the principal investigator. Subjects who have received live or attenuated vaccine in the 4 weeks prior to day 1 subjects with a disease history suggesting abnormal immune function Inability to communicate well with the Investigator (i.e. language problem, poor mental development or impaired cerebral function) Participation in any clinical study for a New Chemical Entity within the previous 16 weeks or a marketed drug clinical study within the previous 12 weeks or within 5 half- lives, whichever is the longer, before the first dose of study drug. Donation of 450 ml or more blood within the previous 12 weeks Women who are pregnant Males who are sexually active with a female partner of childbearing potential and who have not had a vasectomy and who do not agree to double methods of contraception with at least one barrier from day 1 for 90 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single Group Assignment This is a phase 1, dose escalating study to assess safety, tolerability, and PK of a single dose of PRS-060 administered by oral inhalation or IV infusion to healthy male and female subjects. This study will be conducted utilizing a single-blind, randomized, dose-escalating design.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* PRS-060 Matching Placebo<br>|
| Experimental: PRS-060<br> | Drug: PRS-060<br>* Drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events (AEs) after a single inhaled or IV infusion dose of PRS-060. | The number of participants with treatment related AEs as assessed by CTCAE v4.0. Subjects will be monitored for AEs during study participation (beginning at the time study drug is first administered) until 30 days after dosing. | From time of dose until 30 days after dosing. | 
| Change in blood pressure. | To assess blood pressure (systolic and diastolic) as a criterion of safety and tolerability variables. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in heart rate. | To assess changes in beats per minute (BPM) as a criterion of safety and tolerability variables. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in body temperature. | To assess changes in body temperature as a criterion of safety and tolerability variables as measure in degrees Celsius. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in electrocardiograms (ECGs). | To assess changes in cardiovascular system function (change in QTC parameters) as a criterion of safety and tolerability variables. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in FEV1 (Forced expiratory volume 1-second) | To assess changes in FEV1 (Forced expiratory volume 1-second) as measured in L. | Pre-dose and post-dose at 5,10, 20 minutes,1 and 4 hours | 
| Change in FEV6 (Forced expiratory volume 6-seconds) | To assess changes in FEV6 (Forced expiratory volume 6-seconds) as measured in L. | Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours | 
| Change in peak expiratory flow rate (PEFR) | To assess changes in PEFR (Peak expiratory flow rate) as measured in L/s. | Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours | 
| Change in forced vital capacity (FVC) | To assess changes in FVC (Forced vital capacity) as measured by a percentage (%) predicted. | Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours | 
| Change in sodium levels as part of standard serum chemistry panel. | To assess changes in sodium levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in potassium levels as part of standard serum chemistry panel. | To assess changes in potassium levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in chloride levels as part of standard serum chemistry panel. | To assess changes in chloride levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in bicarbonate levels as part of standard serum chemistry panel. | To assess changes in bicarbonate levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in blood urea nitrogen (BUN) / Urea levels as part of standard serum chemistry panel. | To assess changes in BUN/Urea levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in creatinine levels as part of standard serum chemistry panel. | To assess changes in creatinine levels as measured in umol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total protein levels as part of standard serum chemistry panel. | To assess changes in total protein levels as measured in g/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Changes in total albumin levels as part of standard serum chemistry panel. | To assess changes in total albumin levels as measured in g/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total ALP levels as part of standard serum chemistry panel. | To assess changes in ALP levels as measured in U/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total ALT levels as part of standard serum chemistry panel. | To assess changes in total ALT levels as measured in U/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total AST levels as part of standard serum chemistry panel. | To assess changes in total AST levels as measured in U/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total bilirubin levels as part of standard serum chemistry panel. | To assess changes in total bilirubin levels as measured in umol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total indirect bilirubin levels as part of standard serum chemistry panel. | To assess changes in total indirect bilirubin levels as measured in umol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total amylase levels as part of standard serum chemistry panel. | To assess changes in total amylase levels as measured in U/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total lipase levels as part of standard serum chemistry panel. | To assess changes in total lipase levels as measured in U/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total uric acid levels as part of standard serum chemistry panel. | To assess changes in total uric acid levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total creatine kinase (CK) levels as part of standard serum chemistry panel. | To assess changes in total CK levels as measured in U/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total calcium levels as part of standard serum chemistry panel. | To assess changes in total calcium levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total magnesium levels as part of standard serum chemistry panel. | To assess changes in total magnesium levels as measured in mmol/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total lactate dehydrogenase (LDH) levels as part of standard serum chemistry panel. | To assess changes in total LDH levels as measured in U/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total immunoglobulin (IgG) levels as part of standard serum chemistry panel. | To assess changes in total IgG levels as measured in g/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total immunoglobulin (IgA) levels as part of standard serum chemistry panel. | To assess changes in total IgA levels as measured in g/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Changes in total immunoglobulin (IgE) levels as part of standard serum chemistry panel. | To assess changes in total IgE levels as measured in g/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in total immunoglobulin (IgM) levels as part of standard serum chemistry panel. | To assess changes in total IgM levels as measured in g/L. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in hematocrit as part of standard hematology panel. | To assess changes in total hematocrit levels as measured by %. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in red blood cell (RBC) counts as part of standard hematology panel. | To assess changes in total red blood cell (RBC) counts as measured by 10^6/uL. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in platelet (PLT) counts as part of standard hematology panel. | To assess changes in platelet counts as measured by 10^9/uL. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in white blood cell (WBC) counts as part of standard hematology panel. | To assess changes in white blood cell (WBC) counts as measured by 10^3/uL. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in neutrophil percentage as part of standard hematology panel. | To assess changes in neutrophil percentage as measured by %. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in lymphocyte percentage as part of standard hematology panel. | To assess changes in lymphocyte percentage as measured by %. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in eosinophil percentage as part of standard hematology panel. | To assess changes in eosinophil percentage as measured by %. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in basophil percentage as part of standard hematology panel. | To assess changes in basophil percentage as measured by %. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in monocyte percentage as part of standard hematology panel. | To assess changes in monocyte percentage as measured by %. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in clarity as part of a standard urinalysis panel. | To assess changes in clarity of the urine sample. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in specific gravity as part of a standard urinalysis panel. | To assess changes in specific gravity of the urine sample. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in pH as part of a standard urinalysis panel. | To assess changes in pH of the urine sample. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in protein levels as part of a standard urinalysis panel. | To assess changes in protein levels of the urine sample. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in glucose levels as part of a standard urinalysis panel. | To assess changes in glucose levels of the urine sample as measured by a positive or negative result. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in ketone levels as part of a standard urinalysis panel. | To assess changes in ketone levels of the urine sample as measured by a positive or negative result. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in blood levels as part of a standard urinalysis panel. | To assess changes in blood levels of the urine sample as measured by a positive or negative result. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in nitrite levels as part of a standard urinalysis panel. | To assess changes in nitrite levels of the urine sample. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 
| Change in leukocyte esterase levels as part of a standard urinalysis panel. | To assess changes in leukocyte esterase levels of the urine sample. | Screening, day 1, day 2, day 3 and 30 days after dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK assessment: Cmax (observed maximum serum concentration taken directly from the individual concentration-time curve) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours | 
| PK assessment Tmax (Time to reach maximum serum concentration, taken directly from the individual concentration-time curve) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 20 and 40 minutes, 1, 1.5, 2, 3, 4, 8,12,15,18, 36 and 48 hours and at 30 days) | 
| PK assessment: t1/2 (Terminal half-life) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 20 and 40 minutes, 1, 1.5, 2, 3, 4, 8,12,15,18, 36 and 48 hours and at 30 days | 
| PK assessment: AUC(0-last) (Area under the serum concentration-curve from time zero to the time of last quantifiable analyte concentration) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 20 and 40 minutes, 1, 1.5, 2, 3, 4, 8,12,15,18, 36 and 48 hours and at 30 days | 
| PK assessment: AUC (Area under the concentration-time curve in the serum zero (pre-dose) extrapolated to infinite time) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 20 and 40 minutes, 1, 1.5, 2, 3, 4, 8,12,15,18, 36 and 48 hours and at 30 days | 
| PK assessment: AUC(0-24) (Area under the plasma concentration-curve) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 20 and 40 minutes, 1, 1.5, 2, 3, 4, 8,12,15,18, 36 and 48 hours and at 30 days | 
| PK assessment: Vz/F (Apparent volume of distribution during terminal phase) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 20 and 40 minutes, 1, 1.5, 2, 3, 4, 8,12,15,18, 36 and 48 hours and at 30 days | 
| PK assessment: CL/F (Apparent oral clearance estimated as dose divided by AUC) | Evaluation of the PK of a single inhaled or IV infusion dose of PRS-060 | Pre-dose and post-dose at 5, 20 and 40 minutes, 1, 1.5, 2, 3, 4, 8,12,15,18, 36 and 48 hours and at 30 days | 
| PK assessment of urine | Evaluation of PRS-060 levels in the urine after a single inhaled or IV infusion dose of PRS-060 | Pre-dose and continuously during the following time-intervals: 0-4, 4-8, 8-12, 12-18, 18-24, 24-30, 30-36, 36-42 and 42-48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Anticalin, PRS-060, Healthy Volunteers, Pieris, IL-4 receptor alpha, IL-13, IL-4