Inhaled Itraconazole for Allergic Bronchopulmonary Aspergillosis

Recruiting at 17 trial locations

Overseen By Brent Jones, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pulmatrix Inc.

Must not be taking: Systemic azoles, CYP3A4 substrates

Disqualifiers: Congestive heart failure, COPD, others

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

Compensation: Varies

Number of Visits: 6

Duration: 16 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing PUR1900, a medicine you inhale to treat lung infections caused by fungi. It focuses on adults with asthma who also have a fungal lung condition called ABPA. The medicine works by going straight to the lungs to fight the infection. The study will check if PUR1900 is safe and effective for these patients.

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 must not be on medications that interact with itraconazole or have used certain antifungal agents recently. Your asthma medication regimen should be stable before starting the trial.

How does the drug inhaled itraconazole differ from other treatments for allergic bronchopulmonary aspergillosis?

Inhaled itraconazole is unique because it is administered directly to the lungs, which may enhance its effectiveness in treating allergic bronchopulmonary aspergillosis by targeting the site of infection more directly compared to oral medications. This method could potentially reduce systemic side effects and improve drug delivery to the affected area. ^{1 2 3 4 5}

Research Team

Chris Cabell, MD

Principal Investigator

Pulmatrix Inc.

Eligibility Criteria

Adults over 18 with asthma and ABPA who can perform a spirometry test, have an FEV1 ≥50% of predicted normal, and demonstrate correct inhalation technique. They must not be pregnant or planning pregnancy, agree to contraception if applicable, and have stable asthma medication use. Excluded are those with severe liver issues, recent serious infections or surgeries, certain heart conditions, recent azole antifungal use, or history of significant drug/alcohol abuse.

Inclusion Criteria

I have been diagnosed with ABPA based on specific tests and criteria.

I agree to use birth control if I can have children.

Can demonstrate the correct inhalation technique and achieve a minimum inspiratory flow rate of 45 L/min for the use of the delivery device at screening and before dosing on Day 1.

Exclusion Criteria

Has a history of any clinically significant drug or alcohol abuse in the past 6 months before screening, as judged by the Investigator.

I haven't had a serious infection needing strong medication in the last 28 days.

I have no planned surgeries or other studies that could affect this trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive either 40mg or 20mg of PUR1900 or Placebo for 112 days, complete an eDiary, answer questions about their asthma, and perform peak respiratory flow measurements at home. Clinic visits occur approximately once a month.

16 weeks

4 visits (in-person)

Observation

Participants are monitored for safety and effectiveness after treatment, with a final clinic visit at the end of the observation period.

8 weeks

1 visit (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term with the study drug.

Treatment Details

Interventions

• Itraconazole
• Placebo

Trial Overview The trial is testing PUR1900 (Itraconazole Powder) as an inhaled treatment for ABPA in asthmatic patients. It will assess safety/tolerance and the effect on ABPA symptoms over a period including a screening phase (28 days), treatment phase (112 days), and observation phase (56 days). Participants will also record daily health diaries.

Participant Groups

Group I: PUR1900 40 mg Experimental Treatment 1 Intervention

4 PUR1900 (10 mg itraconazole) Capsules with 20 mg total powder (10 mg itraconazole plus 10 mg excipients) administered via oral inhalation, using the RS01 Monodose inhaler once daily for 112 days at approximately the same time each day.

Group II: PUR1900 20 mg Experimental Treatment 1 Intervention

2 PUR1900 (10 mg itraconazole) Capsules with 20 mg total powder (10 mg itraconazole plus 10 mg excipients) and 2 Placebo Capsules with with 11.8 mg total powder (excipients only) administered via oral inhalation, using the RS01 Monodose inhaler once daily for 112 days at approximately the same time each day.

Group III: Placebo Placebo Group 1 Intervention

4 Placebo Capsules with with 11.8 mg total powder (excipients only) administered via oral inhalation, using the RS01 Monodose inhaler once daily for 112 days at approximately the same time each day.

Itraconazole is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Approved in European Union as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Approved in Canada as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Approved in Japan as Sporanox for:

• Fungal infections
• Histoplasmosis
• Aspergillosis
• Blastomycosis

Who Is Running the Clinical Trial?

Pulmatrix Inc.

Lead Sponsor

Trials

16

Recruited

410+

Findings from Research

In a study involving 44 patients with moderate to severe asthma, both fluticasone aerosol combined with theophylline tablets and salmeterol/fluticasone propionate aerosol significantly improved lung function and reduced inflammation markers after 12 weeks of treatment, with no significant differences between the two groups.

Both treatment regimens were found to be safe, as there were no significant abnormalities in blood biochemistry, ECG results, or vital signs, suggesting that fluticasone combined with theophylline could be a viable option for asthma management, especially in primary care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intervention Studies of Inhaled Corticosteroids Combined with Long-acting Theophylline or Long-acting β2-agonists in Patients with Moderate to Severe Asthma: A Randomized, Controlled Study. Wang, Y., Chen, P., Dai, A., et al.[2019]

References

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

Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease. [2019]

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

[Asthma control with the salmeterol-fluticasone-combination disc compared to standard treatment]. [2015]

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

Intervention Studies of Inhaled Corticosteroids Combined with Long-acting Theophylline or Long-acting β2-agonists in Patients with Moderate to Severe Asthma: A Randomized, Controlled Study. [2019]

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

A long-term study of the antiinflammatory effect of low-dose budesonide plus formoterol versus high-dose budesonide in asthma. [2015]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility and development of the fluticasone/formoterol combination formulation (Flutiform(®)) for the treatment of asthma. [2021]