Clinical trial NCT03574805: Study of Multiple Doses of PRS-060 Administered by Oral Inhalation in Subjects With Mild Asthma
Official title: A Dose-Escalating, Single-Blind Study to Assess the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of PRS-060 Administered by Oral Inhalation in Subjects With Mild Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Asthma
Anticalin
PRS-060
Pieris
IL-4 receptor alpha
IL-13
IL-4
Lead sponsor: Pieris Australia Pty Ltd
Sponsor class: INDUSTRY
First posted: 2018-07-02
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study of Multiple Doses of PRS-060 Administered by Oral Inhalation in Subjects with Mild Asthma

Detailed description: PRS-060 is a drug candidate being developed for the treatment of asthma. The main purpose of this study is to investigate the safety, tolerability, and pharmacokinetics of multiple doses of PRS-060 administered by inhalation in subjects with mild asthma.

Eligibility criteria: Inclusion Criteria:

* Body Mass Index (BMI) of 18 to 35
* Subjects who are non-smokers or ex-smokers who have smoked no more than twice in 3 months prior to screening (determined by urine continine \< 500 ng/mL, at Screening visit)
* Males and non-pregnant, non-breastfeeding females
* Males who are sexually active with women of childbearing potential must agree to follow a highly effective method(s) of contraception for the duration of treatment with study drug as well as for an additional 90 days post-treatment completion. Women of childbearing potential who are sexually active with a fertile male must agree to follow instructions for double methods of contraception for the duration of their participation in the trial and for 90 days post-treatment completion
* Documented diagnosis of mild asthma
* 18 to 55 years of age
* Lung function ≥ 70% predicted for FEV1 and FEV1/FVC ratio ≥ 0.7
* FeNO ≥ 35 ppb at Screening and during pre-qualification for the study

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 \[IFN\]-γ release assay \[IGRA\], QuantiFERON® TB-Gold), that may put the subject at risk during participation in the study
* History of cancer within the last 10 years (20 years for breast cancer) except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured. Any history of lymphoma is not allowed
* 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
* Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the Principal Investigator
* Significant history of recurrent ongoing 'dry eye syndrome' of any cause that may be chronic or acute, that may affect the interpretation of safety data associated with the potential for ADAs targeted to PRS-060 (structurally related to tear lipocalin)
* 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
* History of anaphylaxis following any biologic therapy and known history of allergy or reaction to any component of the investigational product formulation
* 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, or breastfeeding, or planning to become pregnant within the study period or 90 days post-treatment completion
* 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 a highly effective method of contraception from Day 1 to 90 days post-treatment completion. Females of childbearing potential who are sexually active with a fertile male partner who do not agree to double methods of contraception with at least one barrier from Day 1 to 90 days post-treatment completion
* Life-threatening asthmatic episode in the past
* C-reactive protein (CRP) above 5 mg/L
* Use of the following medicines within the specified time before screening:

  * Long-acting β2 agonists; none for 4 weeks prior to Screening
  * Anti-IgE or anti-IL-5 therapy; for 6 months prior to Screening
  * Inhaled corticosteroids (\> 500 μg per day of beclometasone dipropionate \[BDP\] or equivalent) within 16 weeks prior to Screening
  * Inhaled corticosteroids; none for 4 weeks prior to screening
  * Oral or injectable steroids for the treatment of asthma or respiratory tract infection within 5 years prior to Screening
  * Intranasal steroids within 4 weeks prior to Screening
  * Topical steroids within 4 weeks prior to Screening
  * Leukotriene antagonists within 2 weeks prior to Screening
  * Xanthines (excluding caffeine), anticholinergics, or cromoglycate within 1 week prior to Screening
  * PRS-060 at anytime

Primary outcomes:
measure: Number of participants with adverse events (AEs) after an inhaled dose of PRS-060
timeFrame: From time of dose until 30 days after dosing
measure: Change in blood pressure
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in heart rate
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in body temperature
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in electrocardiograms (ECGs)
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in forced expiratory volume 1-second (FEV1) as part of spirometry
timeFrame: Screening, during treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in forced vital capacity (FVC) as part of spirometry
timeFrame: Screening, during treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in peak expiratory flow rate (PEFR) as part of spirometry
timeFrame: Screening, during treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in sodium levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in potassium levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in chloride levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days)
measure: Change in bicarbonate levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in blood urea nitrogen (BUN)/Urea levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in creatinine levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in total protein levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in albumin levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in alkaline phosphate (ALP) levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in ALT levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Changes in AST levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in total bilirubin levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in direct bilirubin levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in indirect bilirubin levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in amylase levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in lipase levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in uric acid levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in creatine kinase (CK) levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in calcium levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in magnesium levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in lactate dehydrogenase (LDH) levels as part of standard serum chemistry panel.
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in total immunoglobulin (IgG) levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Changes in total immunoglobulin (IgA) levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Changes in total immunoglobulin (IgE) levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in total immunoglobulin (IgM) levels as part of standard serum chemistry panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in hematocrit as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in hemoglobin levels as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in red blood cells (RBC) counts as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in platelet (PLT) counts as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in white blood cells (WBC) counts as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in neutrophil percentage as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in lymphocyte percentage as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in eosinophil percentage a part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in basophil percentage as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in monocyte percentage as part of standard hematology panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in clarity as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in specific gravity as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in pH as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in protein levels as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in glucose levels as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in ketone levels as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in blood levels as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in nitrite levels as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: Change in leukocyte esterase levels as part of a standard urinalysis panel
timeFrame: Screening, during treatment, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
Secondary outcomes:
measure: PK assessment: Cmax (observed maximum serum concentration taken directly from the individual concentration-time curve)
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: PK assessment: Tmax (time to reach maximum serum concentration, taken directly from the individual concentration-time curve)
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: PK assessment: t1/2(terminal half-life)
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 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: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: PK assessment: AUC (area under the concentration-time curve in the serum zero [pre-dose] extrapolated to infinite time)
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: PK assessment: AUC (0-24) (area under the plasma concentration-curve)
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: PK assessment: Vz/F (apparent volume of distribution during terminal phase)
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: PK assessment: CL/F (apparent oral clearance estimated as dose divided by AUC)
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: PK assessment of urine
timeFrame: During treatment and confinement
measure: Serum ADA assessment using bridging Immunoassay Enhanced Chemiluminescence (ECL) method
timeFrame: During treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
measure: FeNO assessment
timeFrame: Screening, during treatment and confinement, 7 days after dosing (±1 day), and 30 days after dosing (±3 days).
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Q-Pharm
state: Queensland
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
city: Melbourne
country: Australia
facility: Nucleus Network Limited
state: Victoria
city: Nedlands
country: Australia
facility: Linear
state: West Australia
Study officials:
References: