A Safety Study of PC945 (Opelconazole) Prophylaxis or Pre-emptive Therapy Against Pulmonary Aspergillosis in Lung Transplant Recipients (OPERA-S Study)

Recruiting at 24 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

102 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called opelconazole to prevent lung infections caused by Aspergillus fungus in people who have had a lung transplant. The study will last for several months, followed by a safety check. Opelconazole works by stopping the fungus from growing in the lungs, helping to prevent serious infections.

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.

What data supports the effectiveness of the drug PC945 (Opelconazole) for treating lung infections?

Research shows that PC945, an inhaled antifungal drug, is effective against lung infections caused by fungi like Aspergillus and Candida. It has been shown to work well in preclinical studies and in two lung transplant patients with difficult-to-treat infections, without causing significant side effects. ^{1 2 3 4 5}

Is PC945 safe for human use?

PC945, also known as Opelconazole, has been tested in healthy people and those with mild asthma, and it was generally well tolerated. The side effects were mild to moderate and went away before the study ended, with no significant changes in lung function observed. ^{1 4 5 6 7}

Research Team

Vice President Clinical Development

Principal Investigator

Pulmocide Ltd

Eligibility Criteria

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

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

Treatment Details

Interventions

• PC945
• Standard of Care

Participant Groups

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+

Findings from Research

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Tablets or oral suspension for posaconazole in lung transplant recipients? Consequences for trough concentrations of tacrolimus and everolimus. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection. [2020]

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

Posaconazole: An Update of Its Clinical Use. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Update on azole antifungals. [2015]