A Phase 1 Study of AP02 (Nintedanib Solution for Inhalation) Delivered via the PARI eFlow®Nebulizer System in Healthy Volunteers and Patients with Idiopathic Pulmonary Fibrosis orProgressive Fibrosing Interstitial Lung Disease

Phase 1

Completed

• Conditions: Progressive, Fibrosing Interstitial Lung Diseases; Idiopathic Pulmonary Fibrosis; Respiratory - Other respiratory disorders / diseases

• Registration Number: ACTRN12620001141932
• Lead Sponsor: Avalyn Pharma Pty Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-11-02
• Study Completion: 2022-12-12
• Last Update Posted: 23 January 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

A subject must meet all of the following inclusion criteria to be eligible to enroll in the clinical trial:

Inclusion Criteria for all Cohorts:
1. Males or females 18 to 55 years of age.
2. Female subjects must be:
• Of non-childbearing potential [surgically sterilized or post–menopausal (12 months with no menses without alternative medical cause)] OR
• Not pregnant, breast feeding or planning to become pregnant AND willing to comply with the medically acceptable contraceptive requirements of the study from Screening to at least 30 days after the last study drug administration.
3. Must be able to communicate with site personnel and to understand and voluntarily sign the Informed Consent Form (ICF).
4. Have not had any coronavirus disease 2019 vaccines within 7 days of the AP02 dose (Day 1) and, willing to not receive any coronavirus vaccine 7 days after receiving AP02.
5. Have not had any Influenza virus vaccines within 7 days of the AP02 dose (Day 1) and, willing to not receive any Influenza virus vaccine 7 days after receiving AP02.

Additional Inclusion Criteria for Cohort 6 only:
6. Diagnosis of IPF based on American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) 2018 Guidelines OR
Diagnosis of PFILD by at least one of the following criteria within 24 months of screening visit:
a. Clinically significant decline in Forced Vital Capacity (FVC) % predicted based on a relative decline of greater than or equal to 10%
b. Marginal decline in FVC % predicted based on a relative decline of greater than or equal to 5 to less than 10% combined with worsening of respiratory symptoms
c. Marginal decline in FVC % predicted based on a relative decline of greater than or equal to 5 to less than 10% combined with increasing extent of fibrotic changes on chest imaging
d. Worsening of respiratory symptoms as well as increasing extent of fibrotic changes on chest imaging [Note: Changes attributable to comorbidities e.g. infection, heart failure must be excluded. Off label medications used in the clinical practice to treat PFILD include but are not limited to corticosteroid, azathioprine, mycophenolate mofetil (MMF), n-acetylcysteine (NAC), rituximab, cyclophosphamide, cyclosporine, tacrolimus].
7. Males or females 18 to 80 years of age.

Exclusion Criteria

The presence of any of the following exclusion criteria excludes a subject from study enrollment:

Exclusion Criteria for all Cohorts:
1. History of previous allergy or sensitivity to nintedanib.
2. History of reactive airways disease (such as asthma or chronic obstructive pulmonary disease (COPD), cystic fibrosis, or bronchiectasis (Cohorts 1-5 only). Cohort 6 will exclude cystic fibrosis and bronchiectasis but will allow a history of COPD or asthma. Patients with fully resolved childhood asthma with no recurrences or medical needs as an adult are permitted.
3. History of bleeding disorders or currently being treated with anticoagulants.
4. Human Immunodeficiency Virus Positive (HIV+) Result.
5. Active Hepatitis B or C.
6. Cigarette/e-Cigarette smoking or use of other nicotine or tobacco containing products within 7 days prior to study drug administration.
7. Positive for drugs of abuse or alcohol use at screening or admission to Phase 1 facility. A breathalyzer test will be used to screen for the presence of alcohol. A standard urine panel will be used to test for the following substances (with repeat testing for confirmation, as needed) (Cohorts 1-5 only):
• Opiates
• Methadone
• Cocaine
• Tetrahydrocannabinol
• Benzodiazepines
• Amphetamines / Methamphetamines
• Barbiturates
• 3,4-methylenedioxy-methamphetamine
• Phencyclidine
8. Participation in a clinical study with administration of an investigational drug product within the previous 30 days or 5 half-lives (t1/2) of the previously administered investigational product.
9. Donation of blood or significant blood loss within the 8 weeks prior to admission to Phase 1 facility.
10. Donation of plasma within the week prior to admission to Phase 1 facility.
11. Any other condition, which in the view of the investigator is likely to interfere with the study or put the subject at risk.
12. Use of any medication, which in the opinion of the investigator that that might interact with study drug or may lead to abnormal chemistry of hematology tests.
13. Aspartate aminotransferase or alanine aminotransferase (AST or ALT) > 1.5X upper limit of normal.
14. Clinically significant abnormality in the opinion of the principal investigator in baseline hematology or chemistry tests.
15. Use of anti-platelet drugs with the exception of low-dose aspirin for patients in Cohort 6.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of AP02 in normal healthy volunteers (NHV). Safety and tolerability will be assessed by reviewing the incidence and severity of adverse events, serious adverse events and suspected unexpected serious adverse reactions; clinically significant changes from pre-dose to post-dose in physical examination, vital signs, laboratory values, oximetry and spirometry results. Adverse events will be collected from the time of informed consent until the completion of the follow-up visit. Adverse events will be followed until event resolution and will be coded using the Medical Dictionary for Regulatory Activities (MedDRA).[Immediately post-dose, at 24 hours post dose and at 7 days post dose]