None listed
Conditions
Brief summary
Idiopathic Pulmonary Fibrosis (IPF) is a debilitating, progressive lung disease with poor prognosis and limited current treatment. It is characterised by distorted lung architecture, loss of respiratory function, poor quality of life and unresolved pathogenesis. In 2014, the FDA and TGA approved the first two oral drugs for the treatment of IPF, however they only slow the progression of IPF. As such, there continues to be a need for a more effective treatment method for this fatal disease. To address this need, Samumed has developed a small molecule inhibitor of the Wnt pathway, SM04646. Studies have suggested that dysregulation of the Wnt/b-catenin pathway is associated with the pathophysiology of IPF. A number of preclinical pharmacology efficacy studies have been carried out which indicate that SM04646 blocks the progression of lung fibrosis in animal models of IPF. A Phase I study has also been conducted recently in Australia using single ascending doses (SAD) of SM04646 in healthy volunteers. No dose limiting toxicities or serious adverse events were reported. The current study is a Phase I open label, multiple ascending-dose (MAD) safety study of SM04646 inhalation solution in subjects with mild to moderate IPF. SM04646 will be administered as a single use nebulised inhalation. Dose levels will be 2.0mg, 7.0mg, and 20.0mg. Subjects will be treated for 28 consecutive daily doses and will be followed for approximately 30 days after last treatment. Samumed is conducting this trial to evaluate the safety, tolerability and systemic exposure of SM04646 Inhalation solution in IPF patients. Safety monitoring throughout the study will allow for the estimation of the maximum recommended dose to be used for future studies conducted with individuals with IPF
Interventions
This is a Phase 1 Open-Label Study in Subjects with Mild to Moderate Idiopathic Pulmonary Fibrosis (IPF), using a Multiple Ascending Dose (MAD) inhalation of nebulised SM04646.
A previous study has been conducted using single doses of SM04646 in healthy volunteers. This is the first study in humans where multiple doses of SM04646 will be given. It is also the first study where SM04646 will be given to subjects with the health condition of IPF.
SM04646 will be supplied as a single-use nebulize
This is a Phase 1 Open-Label Study in Subjects with Mild to Moderate Idiopathic Pulmonary Fibrosis (IPF), using a Multiple Ascending Dose (MAD) inhalation of nebulised SM04646. A previous study has been conducted using single doses of SM04646 in healthy volunteers. This is the first study in humans where multiple doses of SM04646 will be given. It is also the first study where SM04646 will be given to subjects with the health condition of IPF. SM04646 will be supplied as a single-use nebulized Inhalation Solution in vehicle containing mannitol and tyloxapol. Subjects will be treated with 28 consecutive daily doses of nebulized SM04646 Inhalation Solution and will be followed for approximately 30 days after last treatment. At a minimum, study medication administration on Days 1, 2, 7, 14, 21, and 28 will be performed by qualified and designated study staff at the study centre; on all other dosing days, study medication administration will be performed either at the study site or at the subject’s home with support from a medically qualified staff member. Dose escalation levels will be 2.0 mg, 7.0 mg, and 20.0 mg. Enrollment of subsequent dose level cohorts will occur only after the safety data from the previous dose level cohort are reviewed and approval for dose-escalation is granted by the Safety Review Committee (SRC). Upon review and approval of escalation to a subsequent dose level, no further subjects will be enrolled at the current dose level. The exception to this, however, is if there is a Dose Limiting Toxicity (DLT). A DLT is defined as any of the following occurring within the 28-day dosing period or within follow-up and determined to be at least possibly related to the study medication by the Principal Investigator: * A Grade 3 or higher adverse event (AE) per the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 * A serious adverse event (SAE) The SRC will convene after each DLT and following the completion of the dosing period for each dose level cohort (after Day 28) to determine if further enrolment may continue for a given cohort or if all further enrolment is to cease. If 3 or more unique subjects experience DLTs following the first dose of study medication administration in a given cohort, the Maximum Tolerated Dose (MTD) will be considered exceeded and dosing for the study will cease. If all cohorts are enrolled without exceeding the MTD, the Maximum Recommended Dose (MRD) will be the highest dose cohort enrolled.
Sponsors
Samumed Pacific Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
- Diagnosis of Idiopathic pulmonary fibrosis (IPF) - Forced vital capacity (FVC) greater than or equal to 50% - Lung diffusing capacity (DLCO) greater than or equal to 35% - FEV1/FVC greater than or equal to 0.70 after administration of a bronchodilator - Resting O2 saturation greater than or equal to 90% after 10 minutes at rest on room air - Full understanding of the requirements of the study and willingness and ability to comply with all study visits and procedures - Able to comprehend and willing to sign an informed consent form (ICF) - Able to tolerate and complete placebo (vehicle) inhalation
Exclusion criteria
- Women who are pregnant or lactating - Women who are not post-menopausal who are sexually active and are not willing to use birth control - Males who are sexually active and not willing to use a condom - Males unwilling to refrain from sperm donation - Subjects unwilling to refrain from blood and plasma donation - A history of abuse of prescription or illicit drugs - Positive urine drug screen - Recent occurrence of serious illness requiring hospitalization - Current smoker, or recent history of smoking - Recent use of non-inhaled tobacco- or nicotine-containing products - Regular alcohol abuse - Known hypersensitivity to the active substance or any excipients - Lung transplantation anticipated during the duration of the trial - Receipt of any of the following medication or treatment: a. Nintedanib or Pirfenidone within 7 days prior to screening b. Previous therapeutic radiation treatment of the lungs, mediastinum, or chest wall c. Participation in a clinical research trial that included the receipt of an investigational product or any experimental therapeutic procedure d. Immunosuppressive medications e. Use of any therapy targeted to treat IPF f. Use of any cytokine modulator g. Recent use of a bronchodilator - History of any of the following conditions: a. Pulmonary embolism or pulmonary hypertension b. Poor creatinine clearance c. Active TB infection or history of incompletely treated latent TB infection d. History of malignancy within the last 5 years e. Connective tissue disease f. Congenital respiratory conditions g. Chronic obstructive pulmonary disease (COPD) or asthma h. Recent respiratory tract infection i. Recent acute exacerbation of IPF j. HIV, hepatitis C, or active hepatitis B infection k. Hepatic cirrhosis l. Recent symptomatic coronary artery disease or myocardial infarction (MI) m. Hypertension n. Hypotension o. Any condition that is dependent on oxygen therapy - Any condition that constitutes a risk or contraindication for participation - Abnormal haematology values or blood chemistry values - History of cardiac arrhythmia - Subjects who are immediate family members of personnel directly affiliated with the study at the investigative site, or are directly affiliated with the study at the investigative site - Subjects employed by Samumed Pacific Pty Ltd, or any of its affiliates or development partners (responsible for the conduct of the study) - Subjects who are immediate family members of personnel directly affiliated with the study at the investigative site, or are directly affiliated with the study at the investigative site - Subjects employed by Samumed Pacific Pty Ltd, or any of its affiliates or development partners responsible for the conduct of the study
Outcome results
None listed