Inhaled Itraconazole for Allergic Bronchopulmonary Aspergillosis

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an inhaled antifungal treatment called PUR1900 (itraconazole) for people with asthma who also have allergic bronchopulmonary aspergillosis (ABPA), a lung condition caused by a fungal allergy. The trial aims to determine if PUR1900 is safe, effective, and whether the fungus A. fumigatus develops resistance to it. Participants will receive different doses of the treatment or a placebo and will monitor their asthma symptoms at home. This trial may suit adults with asthma and ABPA who have experienced at least one asthma flare-up requiring steroid treatment in the past year. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important research.

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.

Is there any evidence suggesting that PUR1900 is likely to be safe for humans?

Research shows that the inhaled form of itraconazole, called PUR1900, is generally safe and well-tolerated. Earlier studies found that PUR1900 delivers more medication directly to the lungs and less to the bloodstream. This is positive because it may lead to fewer side effects compared to oral administration. Participants in these studies reported few serious side effects, indicating that the treatment was well-accepted by the body. This inhaled method is designed to treat allergic bronchopulmonary aspergillosis (ABPA), a lung condition in people with asthma. For those considering joining this trial, evidence from past studies suggests that PUR1900 has been safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for Allergic Bronchopulmonary Aspergillosis (ABPA), which often involve oral antifungal medications like itraconazole in pill form, PUR1900 is an inhaled version of itraconazole. This delivery method allows the medication to go directly to the lungs, where it can potentially act more effectively and with fewer systemic side effects. Researchers are excited about this approach because it might offer a more targeted treatment, reducing the need for higher doses and lessening the impact on the rest of the body. Plus, with the potential for better lung-specific efficacy, it could improve symptoms more quickly than existing options.

What evidence suggests that this trial's treatments could be effective for allergic bronchopulmonary aspergillosis?

Research has shown that itraconazole can reduce symptoms and the need for steroids in treating allergic bronchopulmonary aspergillosis (ABPA). In past studies, patients taking itraconazole pills required fewer steroids and experienced fewer flare-ups. This trial will test inhaled itraconazole, specifically PUR1900, which might be safer and more effective than the pill form. The inhaled version targets the lungs directly, potentially improving outcomes for people with ABPA. Overall, itraconazole is considered a promising option for managing ABPA symptoms. Participants in this trial may receive either the PUR1900 40 mg or PUR1900 20 mg inhaled treatment, or a placebo. ^{1 2 3 6 7}

Who Is on the Research Team?

Chris Cabell, MD

Principal Investigator

Pulmatrix Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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.

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJM200003163421102

A Randomized Trial of Itraconazole in Allergic ... We conducted a randomized, double-blind trial of treatment with either 200 mg of itraconazole twice daily or placebo for 16 weeks in patients who met ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02440009

A Randomized Trial of Itraconazole in Acute Stages ... We hypothesize that itraconazole when given in the acute stages of ABPA will decrease the chances of relapse and progression to glucocorticoid-dependent ABPA.

3. journal.chestnet.org journal.chestnet.org/article/S0012-3692(16)37011-8/fulltext

Effects of Itraconazole Therapy in Allergic Bronchopulmonary ... Conclusion. These results demonstrate the efficacy of itraconazole in ABPA in reducing or eliminating the need for glucocorticoid therapy, along with clinical, ...

4. jaci-inpractice.org jaci-inpractice.org/article/S2213-2198(25)00253-3/fulltext

Real-World Effectiveness of Biologic Therapy in Allergic ... Current treatment relies on oral corticosteroids (OCS) and triazole antifungal therapy, but there is increasing evidence of the benefits of biologic therapies.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7098863/

A phase 1/1b study of PUR1900, an inhaled formulation ... 18 Thus, inhaled itraconazole offers the possibility to improve upon both the efficacy and safety profile associated with oral itraconazole in ABPA, a disease ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6483796/

Azoles for allergic bronchopulmonary aspergillosis associated ... Two trials demonstrate that itraconazole reduced the inflammation associated with ABPA and improves clinical outcomes over 16 weeks. As both the intensity ...

7. annallergy.org annallergy.org/article/S1081-1206(18)30936-0/abstract

A PHASE 1/1B STUDY OF AN INHALED FORMULATION ... ITRA was safe and well-tolerated under the study conditions tested, and achieved significantly higher lung and lower plasma exposure compared to oral ...