Clinical trial NCT03384290: Study of a Single Dose of PRS-060 Administered by Oral Inhalation or IV Infusion in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Asthma
Anticalin
PRS-060
Healthy Volunteers
Pieris
IL-4 receptor alpha
IL-13
IL-4
Lead sponsor: Pieris Australia Pty Ltd
Sponsor class: INDUSTRY
First posted: 2017-12-27
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with Adverse Events (AEs) after a single inhaled or IV infusion dose of PRS-060.
timeFrame: From time of dose until 30 days after dosing.
measure: Change in blood pressure.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in heart rate.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in body temperature.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in electrocardiograms (ECGs).
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in FEV1 (Forced expiratory volume 1-second)
timeFrame: Pre-dose and post-dose at 5,10, 20 minutes,1 and 4 hours
measure: Change in FEV6 (Forced expiratory volume 6-seconds)
timeFrame: Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours
measure: Change in peak expiratory flow rate (PEFR)
timeFrame: Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours
measure: Change in forced vital capacity (FVC)
timeFrame: Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours
measure: Change in sodium levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in potassium levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in chloride levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in bicarbonate levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in blood urea nitrogen (BUN) / Urea levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in creatinine levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total protein levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Changes in total albumin levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total ALP levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total ALT levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total AST levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total bilirubin levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total indirect bilirubin levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total amylase levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total lipase levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total uric acid levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total creatine kinase (CK) levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total calcium levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total magnesium levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total lactate dehydrogenase (LDH) levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total immunoglobulin (IgG) levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total immunoglobulin (IgA) levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Changes in total immunoglobulin (IgE) levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in total immunoglobulin (IgM) levels as part of standard serum chemistry panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in hematocrit as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in red blood cell (RBC) counts as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in platelet (PLT) counts as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in white blood cell (WBC) counts as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in neutrophil percentage as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in lymphocyte percentage as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in eosinophil percentage as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in basophil percentage as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in monocyte percentage as part of standard hematology panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in clarity as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in specific gravity as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in pH as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in protein levels as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in glucose levels as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in ketone levels as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in blood levels as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in nitrite levels as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
measure: Change in leukocyte esterase levels as part of a standard urinalysis panel.
timeFrame: Screening, day 1, day 2, day 3 and 30 days after dosing.
Secondary outcomes:
measure: PK assessment: Cmax (observed maximum serum concentration taken directly from the individual concentration-time curve)
timeFrame: Pre-dose and post-dose at 5, 10, 20 minutes,1 and 4 hours
measure: PK assessment Tmax (Time to reach maximum serum concentration, taken directly from the individual concentration-time curve)
timeFrame: 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)
measure: PK assessment: t1/2 (Terminal half-life)
timeFrame: 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
measure: PK assessment: AUC(0-last) (Area under the serum concentration-curve from time zero to the time of last quantifiable analyte concentration)
timeFrame: 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
measure: PK assessment: AUC (Area under the concentration-time curve in the serum zero (pre-dose) extrapolated to infinite time)
timeFrame: 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
measure: PK assessment: AUC(0-24) (Area under the plasma concentration-curve)
timeFrame: 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
measure: PK assessment: Vz/F (Apparent volume of distribution during terminal phase)
timeFrame: 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
measure: PK assessment: CL/F (Apparent oral clearance estimated as dose divided by AUC)
timeFrame: 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
measure: PK assessment of urine
timeFrame: 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
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Limited
state: Victoria
Study officials:
affiliation: Nucleus Network
name: Jason Lickliter, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: