None listed
Conditions
Brief summary
This study is designed to evaluate the anti-inflammatory effect of orally inhaled PB01 as a single dose (30mg) on lung inflammation produced by an orally inhaled LPS challenge in healthy male participants aged 18 and 55 years.
Interventions
PB01 solution for oral inhalation is administered using a nebuliser and consists of PB01 in 20mM sodium phosphate buffer and 500mM sodium chloride, pH7.
A randomised, double blind, placebo-controlled, two period crossover study in healthy male participants. Over the two Treatment Periods, all participants will be randomised to receive a single orally inhaled dose of either 30mg PB01 or Placebo (in either sequence) at each Treatment Period. Investigational Medicinal Product (IMP) will be admin
PB01 solution for oral inhalation is administered using a nebuliser and consists of PB01 in 20mM sodium phosphate buffer and 500mM sodium chloride, pH7. A randomised, double blind, placebo-controlled, two period crossover study in healthy male participants. Over the two Treatment Periods, all participants will be randomised to receive a single orally inhaled dose of either 30mg PB01 or Placebo (in either sequence) at each Treatment Period. Investigational Medicinal Product (IMP) will be administered by an Aerogen Aeroneb Go vibrating mesh nebuliser for a duration of 15 minutes. Participants will be trained on the use of the Aeroneb Go nebuliser. An inhaled lipopolysaccharide (LPS) challenge (30 microgram) will be administered 1 hour post commencement of the IMP dose administration. The total dose of 30 microgram LPS (from Escherichia coli 026:B6 (Sigma)) will be delivered by a total of 5 inhalations using a calibrated breath activated nebuliser. Following Screening, eligible participants will be admitted to the study unit on Treatment Period 1 Day 1 and will be randomised in a 1:1 ratio to receive either PB01 followed by Placebo or Placebo followed by PB01 in a two period crossover design. IMP will be administered on Treatment Period 1 Day 1 followed by the LPS challenge. Administration of the IMP and LPS will be performed at the study unit under the supervision of the clinical site personnel and participants will be confined to the study unit overnight (i.e. 24 hours) and discharged from the study unit after completion of all study procedures on Treatment Period 1 Day 2. There will be a minimum of 24 days and a maximum of 65 days wash-out between dosing on Treatment Period 1 Day 1 and Treatment Period 2 Day 1. At least 72 hrs and no more than 10 days prior to Treatment Period 2 Day 1 participants will attend a Baseline Visit which will include sputum sampling to determine eligibility to continue to Treatment Period 2. On Treatment Period 2 Day 1, participants will be admitted to the study unit for IMP administration followed by the LPS challenge under the supervision of the clinical site personnel and participants will be confined to the study unit overnight (i.e. 24 hours) and discharged from the study unit after completion of all study procedures on Treatment Period 2 Day 2. An End of Study visit will be performed 7 days (+ 5 days) after the last dose of IMP (i.e on Day 8 (+5)). The maximum planned study duration will be 99 days per participant. The investigator is responsible for maintaining accurate IMP accountability records throughout the study. Drug accountability will be performed by the monitor during monitoring visits to reconcile the number of IMP vials dispensed with that used/returned.
Sponsors
Paranta Biosciences Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Able to speak, read and understand English sufficiently to understand the purposes and risks of the study and to provide written informed consent. Healthy males aged 18 to 55 years inclusive at the time of consent. Body Mass Index (BMI) of greater than or equal to 18 to less than or equal to 32.0 kg/m2. Normal pulmonary function and performance on pulmonary function tests, defined as Forced expiratory volume measured in one second, expressed in litres (FEV1), and Forced vital capacity, expressed in litres (FVC) both greater than or equal to 80% of their predicted value for age, ethnicity, sex and height. Participants must be willing and able to comply with scheduled visits, study restrictions, treatment plan, laboratory tests and other study procedures. Participants must be willing not to donate sperm and to comply with the medically acceptable contraceptive requirements of the study from first dose of IMP to 30 days after the last IMP administration. Ability to produce a sputum sample, sufficient to produce at least 50 mg sputum plugs with a viability factor of not less than 40%, total cell count range greater than or equal to 0.50 to less than or equal to 14 x 106 cells per gram, comprising less than or equal to 55% neutrophils, less than or equal to 20% squamous epithelial cells and less than or equal to 3% eosinophils.
Exclusion criteria
Participants will not be eligible to participate in the study if they meet any of the following criteria: Clinically significant respiratory disease including airway inflammation, haemoptysis or other respiratory disease (except for completely-resolved childhood asthma and symptom free for greater than 5 years). Current smokers or ex-smokers who have given up smoking for less than 12 months and/or have a smoking pack history of greater than 5 pack years (1 pack year equals 20 cigarettes per day for 1 year or 5 cigarettes per day for 4 years). Participants with any currently active infection, or who have a previous respiratory tract infection that resolved less than 4 weeks prior to screening or to randomisation, or any other previous infection that resolved less than 7 days prior to screening or to randomisation. Any clinically significant abnormalities on physical examination, medical history, 12-lead electrocardiogram (ECG), or vital signs as judged by the investigator and in consultation with the sponsor if required. Any clinically significant abnormalities on clinical laboratory tests (clinical chemistry, liver function, haematology, coagulation profile and urinalysis) at screening. Note: These screening laboratory samples must be obtained no more than 7 days prior to randomisation. Clinically significant abnormality of renal function, defined as Cockcroft Gault creatinine clearance less than 70 ml/min. Note: These screening laboratory samples must be obtained no more than 7 days prior to randomisation. Clinically significant abnormality of hepatic function defined as AST or ALT greater than 1.5 times the upper limit of normal. Note: These screening laboratory samples must be obtained no more than 7 days prior to randomisation. History or evidence of, or positive test for Hepatitis B, Hepatitis C and HIV. Positive urine drug screen, urine cotinine test or alcohol breath test at screening or prior to randomisation, or a history of drug or alcohol abuse and/or dependence within the past year prior to screening. Administration of any investigational agent within 8 weeks or 5 half-lives (whichever is longer) prior to screening. History of clinically significant allergic disease requiring medical treatment with medications as judged by the investigator and in consultation with the sponsor if required. History of hypersensitivity to follistatin or drugs of the same pharmacological class. Surgical or medical conditions which could significantly alter drug absorption, distribution, metabolism or excretion. Major surgery within 3 months prior to screening or anticipated surgery in the study period. Blood or plasma donation of more than 500 mL during the 3 months prior to screening or randomisation. History of or current clinically-significant gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, oncological, immunological, neurological, ophthalmological, haematological or psychiatric disorder or any other condition, which in the opinion of the investigator and in consultation with the sponsor if required would jeopardize the safety of the participant or the validity of the study results. History of significant drug hypersensitivity, milk protein allergy, hypersensitivity to inhalation challenges, or any history of anaphylactic reactions. Participants who have undergone an lipopolysaccharide (LPS) challenge within the previous month prior to screening or a history of significant adverse reaction to LPS challenge. Unable to use nebuliser. An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.
Outcome results
None listed