Dose-Escalation Study of Artesunate Patients With IPF

A Dose-Escalation Study Evaluating the Safety and Tolerability of Artesunate in Participants With Idiopathic Pulmonary Fibrosis (SAFE-IPF)

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 . This will be a single-center randomized, double-blinded, placebo-controlled study of 20 weeks including up to 4 weeks for screening, followed by 12 weeks of oral artesunate treatment across 3 dose levels (dose escalation every 4 weeks), and 4 weeks of a washout (follow-up) period in participants with Idiopathic Pulmonary Fibrosis (IPF). The primary objective of the study is to evaluate the safety and tolerability of artesunate at 3 dose levels, and to select the dose(s) to carry forward into additional clinical testing. The secondary objective includes exploring the blood biomarkers present in participants with IPF at baseline and to investigate how those biomarkers change following artesunate treatment. The exploratory objectives include assessing the changes in the K-BILD and Leicester cough questionnaire scores and change in pulmonary function after artesunate administration.

Inclusion Criteria

Each participant must meet the following criteria to be enrolled in this study:

1. Age 40 years or older.

2. Diagnosis of IPF based upon ATS/ERS/JRS/ALAT 2018 guidelines (56)

3. FVC percent of predicted ≥ 30%; historical FVC for entry in the study is permitted if within 3 months of screening.

4. Diffusing capacity of lung for carbon monoxide (DLco) (hemoglobin-adjusted) ≥ 25%; historical DLco for entry in the study is permitted if within 3 months of screening.

5. Participants receiving nintedanib, pirfenidone, and/or nerandomilast for the treatment of idiopathic pulmonary fibrosis (IPF), including combination therapy (e.g., nintedanib plus nerandomilast or pirfenidone plus nerandomilast), are eligible for enrollment. All background IPF therapies must be stable for at least 6 weeks prior to the Screening visit and taken continuously with no or only rare interruptions.

6. Female participants of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) and all male participants with sexual partners of childbearing potential agree to use highly effective methods of birth control during their participation in the study and for 60 days after the last administration of study drug. Women of child-bearing potential are defined as any female who has experienced menarche and who is not permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.

   Highly effective methods of birth control are defined as those with 99% or greater efficacy and includes:

   Use of hormonal contraception that inhibits ovulation, administered orally, by injection, implant, transdermal patch, or vaginal ring Vasectomized male partner Sexual abstinence, only if it is the participant's consistent and preferred lifestyle Infertile partner, confirmed by medical evaluation

7. Participants must agree to abstain from egg or sperm donation through 60 days after administration of the last dose of study drug.

8. Able to read and sign a written informed consent form (ICF).

7.3 Exclusion Criteria Participants who meet any of the following criteria will be excluded from the study.

1. Receiving any nonapproved agent intended for treatment of fibrosis in IPF or participation in other treatment clinical trials.
2. Clinical evidence of active infection within 30 days of screening, including but not limited to bronchitis, pneumonia, or sinusitis that can affect FVC measurement during screening.
3. Known acute IPF exacerbation, or suspicion by the Investigator of such, within 3 months of screening.
4. The extent of emphysema is greater than the fibrotic changes on the most recent HRCT scan as determined by PI.
5. Any medical condition, not limited to cardiac, hepatic, renal disease or malignancy, in recent months that will make the participants unsuitable for the study, as judged by the PI.
6. Any of the following liver test results above the listed specified limits: total bilirubin >2× the upper limit of normal (ULN); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3× ULN; alkaline phosphatase (ALP) > 2.5× ULN, pending PI's discretion.
7. Hemoglobin < 10.0 g/dL.
8. Pregnant or lactating.
9. Likely to undergo lung transplantation during the study (being on transplantation list is acceptable).
10. Currently receiving and expected to remain on treatment during the study with drugs interacting with artesunate including amodiaquine, and efavirenz, nevirapine and ritonavir.