Artesunate for Idiopathic Pulmonary Fibrosis

(SAFE-IPF Trial)

Overseen By Evgenios Neofytou, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joseph C. Wu

Must be taking: Nintedanib, Pirfenidone

Must not be taking: Amodiaquine, Efavirenz

Disqualifiers: Active infection, Acute IPF exacerbation, Emphysema, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests artesunate, a drug typically used for malaria, to determine if it can benefit individuals with Idiopathic Pulmonary Fibrosis (IPF), a lung disease that causes scarring and makes breathing difficult. The primary goal is to assess the safety and tolerability of artesunate at various doses in people with IPF. Researchers will also examine blood markers to observe changes before and after treatment. Participants must have IPF and already be on stable doses of other IPF treatments, such as nintedanib or pirfenidone. As a Phase 1 trial, this research aims to understand how artesunate works in people, offering participants the opportunity to be among the first to receive this treatment for IPF.

Will I have to stop taking my current medications?

If you are currently taking nintedanib or pirfenidone for IPF, you can continue as long as the dose has been stable for at least 6 weeks before the study. However, you cannot participate if you are taking amodiaquine, efavirenz, nevirapine, or ritonavir.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that artesunate, a drug commonly used to treat severe malaria, might also help with lung problems. Studies have explored its potential to block proteins that cause lung scarring, offering promise for conditions like Idiopathic Pulmonary Fibrosis (IPF).

Regarding safety, studies have found artesunate to be generally well-tolerated. Its widespread use for malaria provides some confidence about its safety in humans. However, more specific studies are needed to fully understand its effects on lung diseases like IPF.

Research on animals has shown that artesunate can reduce lung injury. However, this remains early-stage research in humans. While the treatment might be safe, its use for lung conditions is still under exploration and closely monitored for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IPF?

Unlike the standard treatments for idiopathic pulmonary fibrosis, which often include antifibrotic medications like pirfenidone and nintedanib, artesunate is derived from the plant Artemisia annua and traditionally used to treat malaria. Researchers are excited about artesunate because it offers a new mechanism of action by potentially reducing lung fibrosis through its anti-inflammatory and antifibrotic properties. This could provide a novel approach to managing this condition, offering hope for more effective symptom relief and improved lung function.

What evidence suggests that artesunate might be an effective treatment for idiopathic pulmonary fibrosis?

Research has shown that artesunate, a medicine often used for malaria, might also help reduce lung scarring in idiopathic pulmonary fibrosis (IPF). Studies have found that artesunate can lower lung inflammation and scarring in lung disease models by blocking certain proteins that cause lung scarring, potentially slowing the disease. Other research indicates that artesunate reduces inflammation and oxidative stress, which benefits lung health. These findings suggest that artesunate might help people with IPF live longer and improve their quality of life. Although initial results are promising, more research is needed to fully understand its effectiveness in treating IPF. Participants in this trial will receive artesunate to further investigate its potential benefits for IPF. ^{1 2 3 6 7}

Who Is on the Research Team?

Joshua Mooney, MD, MS

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 40 or older with Idiopathic Pulmonary Fibrosis (IPF), who are already on stable IPF treatments like nintedanib or pirfenidone. Participants must have a certain level of lung function and agree to use effective birth control. Those with severe other diseases, recent infections affecting lung function tests, specific liver test abnormalities, low hemoglobin levels, or taking certain drugs can't join.

Inclusion Criteria

I have been on a stable dose of nintedanib or pirfenidone for my IPF for at least 6 weeks.

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

I am using or willing to use effective birth control during and for 60 days after the study.

Exclusion Criteria

I have had a sudden worsening of my lung condition in the last 3 months.

Your last chest scan showed more damage from emphysema than from fibrosis.

I don't have any major health issues that would exclude me from the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive artesunate capsules by mouth for 12 weeks to evaluate safety and tolerability at three different doses

12 weeks

7 visits (in-person) over 20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Artesunate

Trial Overview The study is testing the safety and effects of artesunate oral capsules at three different doses in IPF patients over 20 weeks. Artesunate is known for treating malaria but may help reduce lung scarring in IPF. The study includes regular visits for exams, blood samples to check biomarkers related to fibrosis before and after treatment.

How Is the Trial Designed?

Group I: Artesunate Experimental Treatment 2 Interventions

Experimental group

Group II: Placebo Active Control 1 Intervention

Control

Artesunate is already approved in United States, European Union for the following indications:

Approved in United States as Artesunate for:

• Malaria
• Cervical intraepithelial neoplasia (CIN2/3) - Investigational

Approved in European Union as Artesunate for:

• Malaria

Who Is Running the Clinical Trial?

Joseph C. Wu

Lead Sponsor

Trials

3

Recruited

40+

Published Research Related to This Trial

The IFIGENIA trial demonstrated that N-acetylcysteine, when used alongside prednisone and azathioprine, significantly slowed the decline in lung function in patients with idiopathic pulmonary fibrosis over 12 months.

Pirfenidone is the first approved antifibrotic drug for idiopathic pulmonary fibrosis in the EU, showing efficacy in slowing lung function decline and reducing disease progression in over 1,100 patients across four clinical trials, though it may cause side effects like gastrointestinal discomfort and skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of pulmonary fibrosis. New substances and new interventions]. Costabel, U., Bonella, F.[2021]

A 77-year-old man with familial idiopathic pulmonary fibrosis (FIPF) showed significant improvement in symptoms and lung function after being treated with pirfenidone, an antifibrotic agent, for over two years.

This case suggests that pirfenidone may be effective not only for sporadic idiopathic pulmonary fibrosis but also for familial cases, indicating its potential broader applicability in treating different forms of IPF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone Improves Familial Idiopathic Pulmonary Fibrosis without Affecting Serum Periostin Levels. Koga, Y., Hachisu, Y., Tsurumaki, H., et al.[2020]

In a randomized trial with 23 colorectal cancer patients, oral artesunate showed potential anti-cancer effects, with 67% of patients experiencing significant tumor cell apoptosis compared to 55% in the placebo group.

Artesunate was generally well tolerated, and during a median follow-up of 42 months, only 1 patient in the artesunate group experienced cancer recurrence compared to 6 in the placebo group, suggesting a possible benefit in preventing cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. Krishna, S., Ganapathi, S., Ster, IC., et al.[2018]

A comprehensive safety analysis of pirfenidone, involving 789 patients over a median exposure of 2.6 years, shows that it is generally safe and well tolerated for treating idiopathic pulmonary fibrosis (IPF).

The most common side effects were mild to moderate gastrointestinal and skin-related events, with serious liver enzyme elevations occurring in only 2.7% of patients, indicating a low risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis. Valeyre, D., Albera, C., Bradford, WZ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7893118/

Artemisinin and artemisinin derivatives as anti-fibrotic ... In another report, artesunate treatment decreased pulmonary inflammation and lung fibrosis resulting from bleomycin-induced pulmonary fibrosis ...

2. withpower.com withpower.com/trial/phase-1-pulmonary-fibrosis-10-2023-b53ce?fbclid=IwZXh0bgNhZW0CMTEAAR6C8zRosvM-9QTuwxzEia7PjMPkn8V0x9QZnBJ6qXbSfSMYCzDKbXHVaWBHog_aem_Gnp8-V5c2OkZ_ndTkpmQ4Q

Artesunate for Idiopathic Pulmonary Fibrosis Artesunate is known for treating malaria but may help reduce lung scarring in IPF. The study includes regular visits for exams, blood samples to check ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11800322/

State of the ART: Drug Screening Reveals Artesunate as a ... A recent study by Zhang et al. published in the journal Cell employed a drug screening system and identified artesunate (ART) as a promising ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0944711322003385

A review of its therapeutic insights in respiratory diseases Artesunate is promising to treat multiple common respiratory disorders via various mechanisms, such as anti-inflammation, anti-oxidative stress, anti- ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1602581/full

Artemisinin and its derivatives: all-rounders that may ... Artemisinin and its derivatives have anti-viral, anti-inflammatory, anti-fibrotic, immunoregulatory, and anti-cancer activities.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05988463?term=Artesunate&cond=fibrosis&rank=1

Open-Label Dose-Escalation Treatment Study of Patients ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7217791/

Anti-malarial drug, artemisinin and its derivatives for the ... Artesunate treatment attenuated lung injury in paraquat-intoxicated rats via reductions in TGFβ1, IL-10 and TNF-α [70]. 30 mg/kg of artesunate ...