Clinical trial NCT05473533: Study of Single and Multiple Doses of PRS-220 Administered by Oral Inhalation in Healthy Subjects
Official title: A Phase 1, Randomized, Blinded, Placebo Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of PRS 220 Administered by Oral Inhalation in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Idiopathic pulmonary fibrosis (IPF)
Anticalin
PRS-220
Healthy Volunteers
Pieris
CTGF
Lead sponsor: Pieris Australia Pty Ltd
Sponsor class: INDUSTRY
First posted: 2022-07-26
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a phase 1, dose escalating study to assess safety, tolerability, and PK of single and multiple doses of PRS-220 administered by oral inhalation to healthy male and female subjects. This study will be conducted utilizing a blinded, randomized, dose-escalating design.
Primary purpose: TREATMENT

Brief summary: A dose escalating study of PRS-220 administered by oral inhalation in healthy subjects

Detailed description: PRS-220 is a new drug being developed for treatment of idiopathic pulmonary fibrosis (IPF). The main purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of single and multiple ascending doses of PRS-220 in healthy subjects.

Eligibility criteria: Inclusion Criteria:

1. The subject is able to provide written ICF prior to Screening.
2. The subject is healthy male or female (only if female satisfies criteria to be classified as a "woman of non-childbearing potential"), between the ages of 18 and 64 (inclusive) at Screening.

   • Women of non-childbearing potential are defined as:
   * Post-menopausal (12 consecutive months of spontaneous amenorrhea without an alternative medical cause); or is
   * Surgically sterile (having undergone one of the following procedures: hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) and at least six weeks post-sterilization.

   Males must be surgically sterile or abstinent or not engaged in sexual relations with a woman of childbearing potential (WOCBP) or, if engaged in sexual relations with a WOCBP, the subject must agree to consistently use an adequate method of contraception, which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner. A highly effective method of contraception is one that has a failure rate of \< 1% when used consistently and correctly.
3. The subject has a body mass index (BMI) between18 and 32 kg/m2 (inclusive) at Screening.
4. The subject has a forced expiratory volume in one second (FEV1) ≥80% of the predicted value at Screening.
5. Percent predicted forced expiratory volume in one second (ppFEV1) measurements during Screening (any time between Day -28 and Day -2) and Check-in (Day -1) (at least 3 days apart; and, centrally confirmed) with absolute difference \<10 percentage units, ppFEV1.
6. The subject agrees to comply with all protocol requirements.

Exclusion Criteria:

1. The subject has clinically significant (at the discretion of the investigator) abnormalities in physical examination, vital signs, hematology/chemistry/urinalysis, or ECG at Screening that would render a subject unsuitable for inclusion. Including but not limited to:

   * Alanine aminotransferase (ALT) \>1.5× upper limit of normal (ULN), aspartate aminotransferase (AST) \>1.5× ULN, gamma-glutamyl transferase (GGT) \>1.5× ULN, or alkaline phosphatase \>1.5× ULN
   * C-reactive protein (CRP) \>2.9 mg/L
   * After at least five minutes of supine rest, have a systolic blood pressure \<90 or \>140 mmHg or diastolic blood pressure \<40 or \>90 mmHg at Screening
2. The subject has any significant medical condition that may put the subject at risk if participating in this study, at the discretion of the investigator (resolved childhood asthma can be included).
3. The subject has a history of malignancy within the past five years, except for basal cell carcinoma, squamous cell carcinoma, and cervical cancer in situ.
4. The subject has upper respiratory tract infections within 14 days prior to the first dose of the study drug product (Day 1); or lower respiratory tract infection within three months prior to Screening (with regard to COVID 19, sites should adhere to local guidelines).
5. The subject has any clinically significant illness, medical/surgical procedure, or trauma within eight weeks prior to the first dose of the study drug product (Day 1).
6. The subject has any history of smoking (e.g., cigarettes, e-cigarettes/vaping, marijuana, cigars) within one month prior to Screening.
7. The subject has received treatment with another investigational drug product within the past 30 days (or five half-lives or the length of the drug's pharmacodynamic effect, whichever is longer) prior to the first dose of the study drug product (Day 1).
8. The subject has a history of severe allergic reaction to any component of PRS-220 including its excipients.
9. The subject has a history of alcohol and/or other substance abuse or addiction within 12 months prior to Screening, as determined by the investigator, or a positive test result for alcohol or drugs of abuse at Screening or prior to the first dose of the study drug product (Day 1).
10. The subject has taken any of the following medications:

    * Prescription medication or herbal supplements within 14 days (or five half-lives, whichever is longer) prior to the first dose of the study drug product
    * Non-prescription medication, vitamins (e.g., biotin), or minerals within seven days prior to the first dose of the study drug product

    Note: Acetaminophen (paracetamol, \<4 g per day), nonsteroidal anti-inflammatory drugs (NSAID) medication, or salicylic acid containing topical preparation may be used within one day prior to the first dose of the study drug product.
11. The subject is consuming excessive amounts of caffeine, defined as more than four servings of coffee, tea, cola, or other caffeinated beverages per day (one serving is approximately 120 mg of caffeine); or the subject refuses to abstain from caffeine-containing foods or caffeinated beverages (e.g., coffee, tea, cola, energy drinks) within three days prior to Day -1 and until discharge from the clinical research unit.
12. The subject has previously enrolled in this study.
13. The subject has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at Screening.
14. The subject has donated blood or blood products \>450 mL within 30 days before the first dose of study drug product. The subject has donated plasma \>450 mL within seven days prior to the first dose of the study drug product.

Primary outcomes:
measure: Safety & tolerability - AEs
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - SAEs
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - TEAEs
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Vital signs (change in blood pressure)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Vital signs (change in heart rate)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Vital signs (change in body temperature)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Vital signs (change in respiratory rate)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Vital signs (change in oxygen saturation)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - 12-lead ECGs
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Spirometry (FEV1)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Spirometry (PEFR)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Spirometry (FVC)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (sodium)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (potassium)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (chloride)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (calcium)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (magnesium)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (bicarbonate)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (urea/urea nitrogen)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (creatinine)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (albumin)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (bilirubin)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (uric acid)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (creatine kinase)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Serum chemistry (lactate dehydrogenase)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (hematocrit)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (red blood cell count)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (platelet count)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (white blood cell count)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (neutrophil percentage)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (lymphocyte percentage)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (eosinophil percentage)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (basophil percentage)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Hematology (monocyte percentage)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (turbidity)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (specific gravity)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (pH)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (protein)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (glucose)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (ketone)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (blood)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Safety & tolerability - Urinalysis (nitrite)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Tolerability - Taste characteristics
timeFrame: Once after first dose on Day 1 (SAD, MAD) and again on Day 15 (MAD)
Secondary outcomes:
measure: Pharmacokinetics of PRS-220 - Serum concentrations (AUC0-t)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (AUC0-inf)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (AUC0-tau)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (AR)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (Cmax)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (Tmax)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (Kel)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (t1/2)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Pharmacokinetics of PRS-220 - Serum concentrations (MRT)
timeFrame: 29 days (SAD), 57 days (MAD)
measure: Immunogenicity - Anti-drug antibodies (ADA)
timeFrame: 29 days (SAD), 57 days (MAD)
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network Pty Ltd.
state: Victoria
Study officials:
References: