Open-Label Dose-Escalation Treatment Study of Patients With IPF

Study Overview
=================
Brief Summary
-----------------
Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive fibrotic lung disease resulting in increasing shortness of breath, cough, and low oxygen levels as a result of lung tissue scarring . The goal of this open-label (no placebo) study is to evaluate the safety and tolerability of artesunate at three different doses in patients with IPF. The secondary goals are to explore the blood biomarkers present in IPF patients at the beginning of the study and to study how those biomarkers change following treatment with artesunate. Participants will have 7 visits to the study site over 20 weeks which will include physician exams, vital signs, questionnaires, research and safety blood samples, and taking artesunate capsules by mouth for 12 weeks. Artesunate is used world-wide for the treatment of severe malaria but has also been found to block specific proteins that cause lung scarring and may provide an additional treatment to slow the fibrotic process in the lung and improve survival and quality of life for patients with IPF.

Official Title
-----------------
A Dose-Escalation Study Evaluating the Safety and Tolerability of Artesunate in Patients With Idiopathic Pulmonary Fibrosis

Conditions
-----------------
Idiopathic Pulmonary Fibrosis

Intervention / Treatment
-----------------
* Drug: Artesunate Oral Product


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants, aged 40 years or older. Diagnosis of IPF based upon ATS/ERS/JRS/ALAT 2018 guidelines (55). FVC percent of predicted ≥ 40%; historical FVC for entry in the study is permitted if within 3 months of screening. Diffusing capacity of lung for carbon monoxide (DLco) (hemoglobin-adjusted) ≥ 30%; historical DLco for entry in the study is permitted if within 3 months of screening. Participants currently receiving treatment for IPF with nintedanib or pirfenidone are allowed, provided these drugs have been given at a stable dose for at least 6 weeks before the Screening visit (stable dose is defined as the highest dose tolerated by the participant during ≥ 6 weeks). Female participants of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) and all male participants with sexual partners of childbearing potential must use highly effective methods of birth control during their participation in the study and for 60 days after the last administration of study drug. Highly effective methods of birth control are defined as those with 99% or greater efficacy. Participants must agree to abstain from egg or sperm donation through 60 days, after administration of the last dose of study drug. Able to read and sign a written informed consent form (ICF). Exclusion Criteria: Receiving any nonapproved agent intended for treatment of fibrosis in IPF or Participation in other clinical trials. Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, or sinusitis that can affect FVC measurement during screening. Known acute IPF exacerbation or suspicion by the Investigator of such, within 3 months of screening. The extent of emphysema is greater than the fibrotic changes on the most recent HRCT scan as determined by PI. Any medical condition, not limited to cardiac, hepatic, renal disease or malignancy in recent months that will make the patients ineligible for the study, as deemed significant by PI. Any of the following liver function test criteria above specified limits: total bilirubin >2× the upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× ULN; alkaline phosphatase > 2.5× ULN, pending PI's discretion. Hemoglobin levels < 10.0 g/dL. Pregnant or lactating females. Likely to have lung transplantation during the study (being on transplantation list is acceptable). Currently receiving and expected to remain on treatment during the study with: amodiaquine, and efavirenz, nevirapine and ritonavir.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label, dose escalation treatment study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Artesunate<br> | Drug: Artesunate Oral Product<br>* Artesunate capsules administered orally twice daily beginning at 10 mg for 4 weeks, followed by 20 mg for 4 weeks, and then 30 mg for 4 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who experience treatment-related adverse events |  | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
shortness of breath, fibrosis, cough, hypoxemia