Opelconazole for Pulmonary Aspergillosis

No longer recruiting at 26 trial locations

Overseen By Chief Medical Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pulmocide Ltd

Must be taking: Anti-mold medication

Must not be taking: Mold active antifungals

Disqualifiers: Fungal disease, Drug abuse, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a treatment called opelconazole (also known as PC945) to prevent lung infections caused by the fungus aspergillus in lung transplant recipients. Some participants will receive opelconazole, while others will receive the current standard treatment to determine which is more effective at preventing infections. The trial seeks individuals who have recently undergone a lung transplant and have not received other organ transplants. Participants should be prepared to begin the study's treatments shortly after their transplant or following a positive test for aspergillus. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain antifungal treatments or investigational drugs. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that opelconazole, the treatment under study, is generally well-tolerated. Clinical trial data have not revealed any major safety concerns after single or multiple doses. Opelconazole is designed for slow absorption in the lungs and low levels in the rest of the body, reducing the risk of side effects. Additionally, studies suggest it is unlikely to interact with other medications. Overall, the evidence indicates that opelconazole is a safe option for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for preventing pulmonary aspergillosis in lung transplant recipients, which typically involves mold-active antifungal treatments, Opelconazole (PC945) offers a novel approach. This treatment is unique because it is administered directly to the lungs as an inhaled therapy, allowing for targeted action right where the infection risk is highest. Researchers are excited about Opelconazole because its localized delivery could potentially minimize systemic side effects and enhance effectiveness by concentrating the medication in the lungs. This targeted approach might lead to more efficient prevention or treatment of fungal infections in these vulnerable patients.

What evidence suggests that opelconazole might be an effective treatment for preventing fungal aspergillus infections in lung transplant patients?

Research has shown that opelconazole, also known as PC945, could help treat fungal infections, particularly in lung transplant patients. In this trial, participants will receive either opelconazole or the standard of care. Studies have found that opelconazole works well against many fungi, including Aspergillus, in both lab tests and animal studies. One study with mice showed it significantly reduced fungal growth, suggesting potential effectiveness for these infections. Opelconazole has also been tested as an inhaled treatment, which could directly target lung infections. While more research is needed to confirm its effectiveness in people, early results are promising for preventing fungal infections in at-risk patients. ^{2 4 5 6 7}

Who Is on the Research Team?

Vice President Clinical Development

Principal Investigator

Pulmocide Ltd

Are You a Good Fit for This Trial?

Inclusion Criteria

Subject or Legally Authorized Representative has provided written or electronic informed consent in a manner approved by the applicable Institutional Review Board (IRB) or Ethics Committee

Subject is able to perform and willing to comply with the study visits, laboratory assessments, and other study-related procedures

You don't have any signs of a lung infection caused by fungus.

Exclusion Criteria

Subject who would normally receive nebulized amphotericin B as the only mold active antifungal agent as initial SoC prophylaxis or pre-emptive therapy

Subject has received a mold active antifungal agent post transplant (Note: a subject who receives a mold active antifungal agent within 24 hours before, during, or after the transplant procedure will not be excluded if the mold active medication was stopped within 72 hours of returning to the ICU after the transplant surgery, or prior to randomization (whichever happens first)

Subject who is receiving, or who is due to receive at any time during the study, an investigational medicinal agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prophylaxis or Pre-emptive Therapy

Participants receive opelconazole or standard of care for prevention or pre-emptive therapy against pulmonary aspergillosis

12 weeks

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PC945
• Standard of Care

How Is the Trial Designed?

Group I: Opelconazole Experimental Treatment 1 Intervention

14.8 mg opelconazole administered twice daily for 12 weeks

Group II: Standard of Care (SoC) Active Control 1 Intervention

Mold-active SoC prophylaxis/pre-emptive therapy

PC945 is already approved in European Union, United States for the following indications:

Approved in European Union as Opelconazole for:

• Aspergillosis

Approved in United States as Opelconazole for:

• Invasive Pulmonary Aspergillosis (IPA)

Who Is Running the Clinical Trial?

Pulmocide Ltd

Lead Sponsor

Trials

10

Recruited

530+

Published Research Related to This Trial

PC945 is a novel inhaled antifungal agent specifically designed to target pulmonary Aspergillus infections, showing potent efficacy in preclinical studies and well-tolerated in healthy volunteers and asthmatics with limited systemic exposure.

In two lung transplant patients with invasive pulmonary Aspergillus infections resistant to other treatments, PC945 successfully treated the infection without causing systemic side effects, highlighting its potential as a safe and effective option for immunocompromised individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections. Murray, A., Cass, L., Ito, K., et al.[2020]

PC945, a new antifungal triazole delivered via nebulization, showed significantly higher concentrations in the lungs compared to plasma, which may enhance its effectiveness against lung Aspergillus infections while minimizing systemic side effects.

The drug was well tolerated in clinical trials with healthy subjects and those with mild asthma, showing only mild to moderate adverse events and no significant changes in lung function, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent. Cass, L., Murray, A., Davis, A., et al.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05238116

Study Details | NCT05238116 | Safety and Efficacy of ...

A double-blind, randomized, placebo-controlled study to assess the safety and efficacy of nebulized PC945 when added to systemic antifungal therapy.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7765807/

PC945, a Novel Inhaled Antifungal Agent, for the Treatment ...

PC945 was found to be effective against a broad spectrum of pathogenic fungi, including Aspergillus spp. Candida spp., Trichophyton rubrum, ...

3.

academic.oup.com

academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaf384/8292774

In vitro and clinical data demonstrate negligible risk of drug ...

Positive control compounds showed >30-fold greater induction outcomes than with opelconazole (omeprazole for CYP1A2 and rifampicin for CYP3A4).

4.

pulmocide.com

pulmocide.com/opelconazole/

Opelconazole - A potent inhaled antifungal

Opelconazole has already shown significant efficacy against Aspergillus fumigatus in an immunocompromised mouse model, exhibiting more than a 47-fold increased ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05238116?intr=Opelconazole&rank=2

Study Details | Safety and Efficacy of PC945 (Opelconazole) in ...

An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

6.

file.medchemexpress.com

file.medchemexpress.com/batch_PDF/HY-117766/PC945-SDS-MedChemExpress.pdf

Safety Data Sheet

Ensure adequate ventilation. Provide accessible safety shower and eye wash station. Personal protective equipment. Eye protection. Safety ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7749516/

Safety and nonclinical and clinical pharmacokinetics of ...

PC945 pharmacokinetics translated from nonclinical species to humans showed slow absorption from lungs and low systemic exposure.