Artesunate for Idiopathic Pulmonary Fibrosis

(DIAMOND 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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Artesunate for treating idiopathic pulmonary fibrosis?

Research suggests that Artesunate, a drug commonly used to treat malaria, may also help with lung diseases by affecting certain pathways in the body that are involved in lung scarring (pulmonary fibrosis). Additionally, Artesunate has shown potential in treating various cancers, indicating its broader therapeutic effects. ^{1 2 3 4 5}

How is the drug Artesunate different from other treatments for idiopathic pulmonary fibrosis?

Artesunate is unique because it is derived from artemisinin, a compound traditionally used to treat malaria, and its use in idiopathic pulmonary fibrosis (IPF) is novel compared to existing antifibrotic drugs like pirfenidone, which are specifically designed to slow lung function decline in IPF. ^{6 7 8 9 10}

Research Team

Joshua Mooney, MD, MS

Principal Investigator

Stanford University

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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.

Participant Groups

Group I: Artesunate Experimental Treatment 1 Intervention

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+

Findings from Research

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 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]

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 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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Artesunate restraining MAPK passage by smad7 to resist pulmonary fibrosis. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Artesunate: A review of its therapeutic insights in respiratory diseases. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The effects of artesunate on the expression of EGFR and ABCG2 in A549 human lung cancer cells and a xenograft model. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Pirfenidone Improves Familial Idiopathic Pulmonary Fibrosis without Affecting Serum Periostin Levels. [2020]

7. Iran pubmed.ncbi.nlm.nih.gov

Comparison of Longevity in Patients with Idiopathic Pulmonary Fibrosis Using Pirfenidone Versus Triple Therapy with Prednisolone, Azathioprine, and Acetylcysteine. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of pulmonary fibrosis. New substances and new interventions]. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A multicentre retrospective observational study on Polish experience of pirfenidone therapy in patients with idiopathic pulmonary fibrosis: the PolExPIR study. [2021]

10. Australia pubmed.ncbi.nlm.nih.gov

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis. [2022]