PC945 + Antifungal Therapy for Invasive Pulmonary Aspergillosis

Recruiting at 200 trial locations

Overseen By Senior Medical Director of Clinical Development

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pulmocide Ltd

Must be taking: Antifungal therapy

Must not be taking: Investigational agents

Disqualifiers: Allergy, Hypersensitivity, Others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

123 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PC945 (also known as Opelconazole), inhaled through a nebulizer, to determine its effectiveness alongside other antifungal medicines for invasive pulmonary aspergillosis (IPA). Researchers aim to discover if adding PC945 benefits patients when other treatments fall short. Participants must have a confirmed IPA infection that hasn't improved with standard antifungal treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking an investigational drug without regulatory approval, you may not be eligible to participate.

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

Research shows that PC945, an inhaled medicine, is being tested for safety and effectiveness against lung infections. Studies have found it to be generally safe for use. The treatment involves inhaling the medicine through a nebulizer, which delivers it directly to the lungs. Early results suggest that side effects are usually mild, such as cough or throat irritation. Importantly, early patient reports have not directly linked any serious health problems to the drug.

This treatment is in a later stage of testing, indicating that substantial safety information is already available. Earlier tests would have ceased if major safety concerns had arisen. Overall, PC945 appears promising for treating serious lung infections, with safety data supporting its use in clinical settings. ^{1 2 3 4 5}

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

Researchers are excited about PC945 for invasive pulmonary aspergillosis because it introduces a new delivery method by being administered directly to the lungs via a nebulizer. This targeted approach allows the drug to act at the site of infection, potentially increasing its effectiveness and reducing systemic side effects compared to oral or intravenous antifungals. Additionally, PC945 is designed to complement existing antifungal therapies, offering a synergistic effect that might enhance treatment outcomes for patients with this serious condition.

What evidence suggests that PC945 might be an effective treatment for invasive pulmonary aspergillosis?

Research has shown that PC945, an inhaled medicine, may help treat invasive pulmonary aspergillosis (IPA), a serious lung infection. In this trial, some participants will receive PC945 alongside their regular treatment, while others will receive a placebo. Early results from patients who used PC945 showed positive effects. Studies provide strong evidence from lab tests and early clinical reports that PC945 can help manage this infection. The treatment targets the fungus in the lungs directly, potentially making it a strong addition to current antifungal treatments. Overall, the data so far are encouraging for those facing this difficult condition. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with a confirmed or likely diagnosis of invasive pulmonary aspergillosis (IPA) that hasn't improved despite standard antifungal treatment. Participants must not have allergies to PC945 or placebo components, should not have used PC945 before, and can't be in another clinical study.

Inclusion Criteria

Participant has proven or probable IPA according to the modified 2019 European Organization for Research and Treatment of Cancer/ Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) consensus definitions or according to the 2010 International Society for Heart and Lung Transplantation (ISHLT) consensus statements for the definitions of infections in cardiothoracic transplant recipients

My fungal infection didn't improve after proper treatment.

Exclusion Criteria

Participant who has recently received, is receiving or due to receive at any time during the study, an investigational medicinal agent that does not have any regulatory approved indications. Subjects who are participating in any other trials e.g., Observational, diagnostic or using medications with an approved indication may be allowed to participate after consultation with the sponsor on an individual basis

Participant with a known or suspected concomitant medical condition or post-surgery complication that, in the opinion of the Investigator, may jeopardize adherence to the protocol requirements or impede the accurate measurement of efficacy or may be an unacceptable additional risk to the Participant should he/she participate in the study

I have previously taken the medication PC945.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nebulized PC945 or placebo twice daily in combination with systemic antifungal therapy

8 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PC945
• Placebo

Trial Overview The trial tests the effectiveness of an inhaled drug called PC945 combined with other systemic antifungal treatments against IPA. Some participants will receive PC945 while others will get a placebo, alongside their usual antifungal therapy.

How Is the Trial Designed?

Group I: PC945 Experimental Treatment 1 Intervention

PC945 dose, administered via nebulizer, twice daily

Group II: Placebo Placebo Group 1 Intervention

PC945-placebo administered via nebulizer, twice daily

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, 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]

PC945, a novel triazole, demonstrated potent antifungal effects against Aspergillus fumigatus in immunocompromised mice, significantly reducing lung fungal loads and associated biomarkers compared to standard treatments like posaconazole and voriconazole.

Extended prophylaxis with low-dose PC945 was more effective than shorter treatment regimens, indicating that repeated dosing enhances its efficacy, suggesting its potential as a new inhaled therapy for treating fungal infections in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice. Kimura, G., Nakaoki, T., Colley, T., et al.[2018]

Recent advancements in the management of invasive aspergillosis include the development of potent and relatively non-toxic antifungal drugs, which have led to safer and earlier interventions, resulting in reduced mortality rates and improved patient outcomes.

Voriconazole is now the preferred drug for primary therapy, while posaconazole is emerging as a promising prophylactic option; however, there are concerns about the emergence of less-susceptible Aspergillus species during treatment, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future therapeutic options in the management of invasive aspergillosis. Krishnan-Natesan, S., Chandrasekar, PH.[2021]

In a study comparing generic amphotericin B to the brand name Fungizone in rabbits with invasive pulmonary aspergillosis, both formulations showed similar efficacy and safety profiles.

The research indicates that generic amphotericin B can be a suitable alternative to Fungizone for treating this serious fungal infection, especially during the drug shortage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of generic amphotericin B in experimental pulmonary aspergillosis. Petraitis, V., Petraitiene, R., Lin, P., et al.[2018]

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]

Intravenous antifungals, specifically amphotericin B and echinocandins, showed an overall response rate of 61% in treating chronic pulmonary aspergillosis (CPA) based on a meta-analysis of 12 studies involving 380 patients.

While liposomal amphotericin B was generally well tolerated, it caused renal function loss in 25% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous therapy for chronic pulmonary aspergillosis: A systematic review and meta-analysis. Bongomin, F., Asio, LG., Olum, R., et al.[2021]

In a murine model of invasive pulmonary aspergillosis, preexposure to itraconazole (ITC) significantly reduced the efficacy of amphotericin B (AMB), with survival rates dropping from 60% in non-ITC-preexposed mice to 0-20% in ITC-preexposed mice at higher AMB doses.

Mice preexposed to ITC showed a consistently higher fungal burden in the lungs, indicating that ITC may antagonize the effects of AMB, as evidenced by significant increases in viable fungal counts and chitin levels, suggesting that prior treatment with ITC could impair the effectiveness of subsequent AMB therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Itraconazole preexposure attenuates the efficacy of subsequent amphotericin B therapy in a murine model of acute invasive pulmonary aspergillosis. Lewis, RE., Prince, RA., Chi, J., et al.[2021]

Higher doses of amphotericin (5 mg/kg/d) using lipid carriers can be safely administered to treat pulmonary invasive aspergillosis in immunocompromised patients, potentially improving outcomes compared to the standard dose of 1 to 1.25 mg/kg/d.

Intraconazole is an effective follow-up treatment after amphotericin for managing pulmonary invasive aspergillosis, providing a sequential therapy approach for better disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Curative antifungal treatment of invasive pulmonary aspergillosis]. Andrès, E., Courouau, F., Kurtz, JE., et al.[2013]

In a study of 20 patients with invasive aspergillosis treated with itraconazole, 75% achieved complete remission, suggesting itraconazole is an effective alternative to traditional therapies like amphotericin B.

A review of 12 published studies indicated an overall response rate of 63% for itraconazole in treating invasive aspergillosis, highlighting its potential as a viable treatment option for immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapy of invasive aspergillosis with itraconazole: our own experiences and review of the literature]. Kreisel, W.[2013]

In a study of 5,410 patients with invasive pulmonary aspergillosis (IPA), voriconazole was the most commonly prescribed initial treatment, used by 49% of patients, followed by fluconazole (11%) and posaconazole (7%).

The majority of patients remained on voriconazole (80%) or isavuconazole (78%) during treatment, while those starting with fluconazole, echinocandins, or posaconazole were more likely to switch medications, indicating potential challenges with these alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment pathways, switches, and inappropriate treatment during invasive pulmonary aspergillosis: real-world experiences from a global research network study. Henao-Martínez, AF., Chastain, DB., Thompson, GR.[2023]

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 ... The outcome of PC945 treatment has been reported in the first two patients who developed invasive pulmonary aspergillosis due to infections with ...

3. pulmocide.com pulmocide.com/opelconazole/

Opelconazole - A potent inhaled antifungal Robust data from in vitro, in vivo, and clinical outcomes in patients with refractory invasive pulmonary aspergillus supported studying opelconazole in a Phase ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20543271

Clinical Trials The purpose of this study is to assess the effectiveness of nebulized PC945 in combination with systemic antifungal therapy for the treatment of refractory ...

5. 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 ... ... invasive pulmonary aspergillosis (IPA). Following 14 days of twice daily dosing, plasma concentrations were expected to be within 80% of ...

6. 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 ...