Artesunate for Pulmonary Arterial Hypertension

((STOP-PAH) Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Joseph C. Wu

Must be taking: PDE5 inhibitors, guanylate cyclase stimulators

Disqualifiers: Serious concomitant morbidity, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called artesunate for individuals with pulmonary arterial hypertension (PAH), a condition where high blood pressure affects the arteries in the lungs. The main goal is to determine if taking artesunate daily is safe and tolerable for those with PAH who are already on other treatments. Participants will take varying doses over several weeks to identify the optimal and safest amount. Suitable candidates for this trial are those with PAH who are on at least two other treatments and still experience symptoms that impact their daily lives. 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 new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should already be on certain treatments for pulmonary arterial hypertension, so you might continue those.

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

Previous studies have examined the safety of artesunate in various situations. The research shows that intravenous artesunate generally does not cause major safety issues in trauma patients and is usually well-tolerated. However, limited information exists on its safety when taken orally, especially at the doses planned for this study.

Artesunate is already approved for treating severe malaria, indicating its safety in those cases. However, this trial is in an early phase, primarily focusing on assessing its safety in humans. Researchers are still gathering information to ensure its safety for treating pulmonary arterial hypertension, a type of high blood pressure affecting the lungs.

Possible side effects of artesunate include changes in blood cell counts and, in rare cases, more serious issues like seizures or organ problems. The trial will closely monitor participants for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Artesunate is unique because it offers a new approach to treating pulmonary arterial hypertension (PAH) by leveraging its anti-inflammatory and anti-proliferative properties. Unlike current treatments like endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogs, which primarily focus on dilating blood vessels or preventing blood clot formation, artesunate targets the underlying biological processes that contribute to the disease. Researchers are excited about artesunate because it could address the progression of PAH more effectively, potentially improving outcomes for patients with this challenging condition.

What evidence suggests that artesunate might be an effective treatment for pulmonary arterial hypertension?

Research suggests that artesunate, the investigational treatment in this trial, might help treat pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the lungs. Studies have shown that artesunate can help blood vessels relax by utilizing nitric oxide, a natural chemical in the body. Animal studies found that it also reduces the thickening of blood vessel walls. These effects indicate that it could improve blood flow in people with PAH. While more research is needed in humans, these early results are promising. ^{1 6 7 8 9}

Who Is on the Research Team?

Roham Zamanian, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for patients with Pulmonary Arterial Hypertension (PAH). Specific eligibility criteria are not provided, but typically participants would need to have a confirmed diagnosis of PAH and be in stable condition to participate.

Inclusion Criteria

My heart and lung condition is stable even after taking various treatments.

Exclusion Criteria

Participants with serious concomitant morbidity per investigator assessment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral artesunate in a dose-escalation study

20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment during a washout period

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Artesunate

Trial Overview The study is testing the safety and how well people can tolerate different doses of an oral medication called Artesunate. It's a Phase 1 trial that lasts for 20 weeks at a single center where everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Open Label Treatment Arm Experimental Treatment 1 Intervention

Dose escalating study with a Follow-up (washout) Period: Total study period of the open-label study: 14 weeks Screening Period: up to 4 weeks Treatment Period (20 mg TID): 4 weeks Treatment Period (40 mg TID): 4 weeks Treatment Period (60 mg TID): 4 weeks Follow-up (washout) Period: 2 weeks after treatment period ends

Who Is Running the Clinical Trial?

Joseph C. Wu

Lead Sponsor

Trials

3

Recruited

40+

Published Research Related to This Trial

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]

Artesunate, an antimalarial drug, is rapidly converted to its active form, dihydroartemisinin, with peak levels of artesunate reached within 5 minutes and dihydroartemisinin within approximately 37.5 minutes after oral administration in rats.

The conversion and absorption of artesunate are influenced by the pH of the gastrointestinal tract, leading to faster absorption in the stomach compared to higher pH environments, which affects the drug's overall efficacy and action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of artesunate after single oral administration to rats. Olliaro, PL., Nair, NK., Sathasivam, K., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06872112

NCT06872112 | A Study Evaluating the Safety and ... This is a 20-week, Phase 1, single-center, open-label, dose-escalation study evaluating the safety and tolerability of daily oral artesunate in patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9232380/

Artemisinin and Its Derivate Alleviate Pulmonary Hypertension ... These results suggest that ARS administration attenuates vascular constriction in a NO-dependent manner. Figure 1. Figure 1. Open in a new ...

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

A review of its therapeutic insights in respiratory diseases Recent studies have found that artesunate may have multiple pharmacological effects, indicating its significant therapeutic potential in multiple respiratory ...

4. researchgate.net researchgate.net/publication/361396548_Artemisinin_and_Its_Derivate_Alleviate_Pulmonary_Hypertension_and_Vasoconstriction_in_Rodent_Models

(PDF) Artemisinin and Its Derivate Alleviate Pulmonary ... Conclusions: In conclusion, these results indicate that treatment with ARS or DHA can inhibit PA vasoconstriction, PASMC proliferation and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7691927/

Long-term outcomes in pulmonary arterial hypertension by ... The Patient Registry for the Characterization of Primary Pulmonary Hypertension reported a median survival of almost six years for patients in FC I or FC II ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10425486/

Safety and efficacy of artesunate treatment in severely ... This study aimed at determining whether intravenous artesunate is safe and effective in reducing multiple organ dysfunction syndrome in trauma patients with ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/213036s004lbl.pdf

artesunate for injection - accessdata.fda.gov No notable safety issues were identified in limited published safety and outcome data for Artesunate for ... artesunate is rapidly converted to DHA by blood ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/artesunate-amivas-epar-product-information_en.pdf

Artesunate Amivas, INN-Artesunate There are insufficient clinical data to establish the safety and efficacy of Artesunate Amivas in infants below 6 months of age. Pharmacokinetic modelling ...

9. go.drugbank.com go.drugbank.com/drugs/DB09274

Artesunate: Uses, Interactions, Mechanism of Action Data regarding overdoses of artesunate are rare. ... Patients experiencing an overdose may present with pancytopenia, melena, seizures, multiorgan failure, and ...