Health Condition 1: B441- Other pulmonary aspergillosis
Conditions
Interventions
Intervention1: PUR1900: 10mg, 20mg or 35mg of PUR1900 using Dry Powder Inhaler, once daily for 28 days
Control Intervention1: Placebo: Placebo will be administered orally using Dry Powder Inhaler, onc
Sponsors
Pulmatrix Inc
PPD Pharmaceuticals Development India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Can provide written informed consent before the performance of any study-specific procedures. 2. Is a male or female, 18 to 75 years old (inclusive) at the time of signing the informed consent. 3. Has a body mass index of 18.0 to 35.0 kg/m2 (inclusive) at screening. 4. Has a historical diagnosis of asthma, as per the Global Initiative for Asthma (GINA) 2018 update. 5. Has a confirmed historical diagnosis of ABPA, as per the Modified International Society for Human and Animal Mycology (ISHAM) working group 2013 criteria. 6. Is currently considered to be in one of the following stages of ABPA: Stage 2 (Response), Stage 4 (Remission), Stage 5a (Treatment-dependent ABPA), or Stage 5b (Glucocorticoid-dependent asthma) (Section 13.3). 7. Has a serum immunoglobulin (Ig) E =1000 IU/mL during screening (Visit 1 or Visit 2). 8. Can perform a valid, reproducible spirometry test with demonstration of a prebronchodilator FEV1 =50% of predicted normal for age, sex, race, and height at a screening visit. 9. Has a documented stable asthma medication regimen during screening (Day -28 to Day 1), including SABA, LABA, and LTRA use and inhaled and/or oral GCS. 10. Subjects who are sexually active, male subjects able to father a child, and female subjects of childbearing potential must agree to follow the contraception requirements outlined in Section 5.8.4 of this protocol. 11. Can demonstrate the correct inhalation technique for the use of the delivery device at screening and before dosing on Day 1. 12. Is willing and able to comply with all study procedures and assessments, including scheduled visits, drug dosing plan, study procedures, laboratory tests, and study restrictions.
Exclusion criteria
Exclusion criteria: 1. Has used any anti-IgE (eg, Xolair® [omalizumab]) or anti-interleukin-5 (IL-5) biologics (eg, Cinqair® [reslizumab], Nucala® [mepolizumab], or Fasenra® [benralizumab]) in the 6 months before first dose of study drug. 2. Is a female of childbearing potential who is pregnant or lactating or who plans to become pregnant during the study (all female subjects must have a negative pregnancy test at screening and predose on Day 1). A woman is considered to be of childbearing potential unless she is either permanently sterile (hysterectomy, bilateral salpingectomy, bilateral oophorectomy, bilateral tubal occlusion/ligation) or postmenopausal (had no menses for 12 months without an alternative medical cause). 3. Is taking or has taken any prescribed or over-the-counter (OTC) drug that is a CYP3A4 inhibitor or substrate in the 14 days (or 5 half-lives, whichever is longer) before first dose of study drug and for the duration of the study (exclusion also applies to the whole fruit or juices of grapefruit and Seville or pomelo oranges). 4. Is taking or has taken any herbal remedies or CYP3A4 inducers in the 28 days before first dose of study drug. 5. Has used any systemic azole antifungal agent in the 6 months before first dose of study drug. 6. Has a history of life-threatening asthma within the last 5 years, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest, and/or hypoxic seizures. 7. Had an occurrence of asthma or ABPA exacerbations within the 28 days before screening or during the 28-day period before Day 1. 8. Had an occurrence of clinically significant bacterial, viral, or fungal infection that required systemic (oral or intravenous) antibiotics, antivirals, or antifungals within the 28 days before screening. Topical treatments, other than antifungals, are allowed. 9. Received any investigational medical product in a clinical research study within the previous 3 months before dosing in this study. 10. Is a study site employee, an immediate family member of a study site employee, or a sponsor employee. 11. Has previously received PUR1900. 12. Has a history of any significant drug or alcohol abuse in the past 2 years before screening, as judged by the investigator. 13. Has current tobacco or inhaled marijuana use or history of smoking tobacco or marijuana within the last 6 months before screening. 14. Is a current user of e-cigarettes or has used these products within the last 6 months before screening. 15. Has the absence of suitable veins for multiple venipunctures/cannulation as assessed by the investigator or designee at screening. 16. Has evidence or history of clinically significant abnormal serum chemistry, hematology, or urinalysis at screening, as judged by the investigator (particularly elevation of liver enzymes or bilirubin). 17. Has a positive urine test result for drugs of abuse, alcohol, or cotinine at screening (unless, in the opinion of the investigator, this can be explained by the subject’s current medications). 18. Has a positive human immunodeficiency virus (HIV; type A and type B) antibody result: a subject who is HIV antibody positive is not excluded if a subsequent CD4 count is =200 cells/µL. 19. Has evidence or a history of clinically
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Primary outcome to evaluate safety and tolerability will be measured by: • Incidence of treatment-emergent adverse events • Incidence of intraday FEV1 declines (from predose to postdose) of =10%, =15%, and =20% • Vital sign measurements (respiratory rate, blood pressure, heart rate, oxygen saturation by pulse oximetry, oral or tympanic temperature) • Physical examination findings • Clinical laboratory parameters • 12-Lead electrocardiogram findingsTimepoint: Time Frame: From Day 1 through Follow Up (which is 7 to 10 days after the last dose) | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the pharmacokinetics of multiple doses of inhaled PUR1900 in plasma and sputumTimepoint: Pharmacokinetic parameters of itraconazole and hydroxy-itraconazole in plasma, including, but not limited to, Cmax, Tmax, AUC, CL/F, and Vz/F Sputum concentrations of itraconazole and hydroxy-itraconazole on Day 2, on Day 14, and at follow-up;To evaluate the effect of PUR1900 on biomarkers of inflammation (sputum eosinophils and serum IgE)Timepoint: Change from baseline (Day -9 to Day -6) to Day 28 in sputum eosinophil count Change from baseline (Day -9 to Day -6) to Day 28 in percentage of sputum eosinophils Change from baseline (Day 1) to Day 28 in IgE plasma concentration;To evaluate the effect of PUR1900 on pulmonary function following single- and multiple-dose administration of PUR1900Timepoint: Change from baseline (Day 1) to Day 28 in FEV1 Change from baseline (Day 1) to Day 28 in FVC, PEF, and FEV1/FVC;To evaluate the effect of PUR1900 on the Aspergillus fumigatus burden in the sputum, as assessed by quantitative PCR and sputum cultureTimepoint: Change from baseline (Day 1) to Day 28 in A fumigatus burden in sputum as assessed by quantitative PCR and sputum culture;To evaluate the impact of PUR1900 on respiratory symptoms, as measured by the ACQ-6Timepoint: Change from baseline (Day 1) to Day 28 in ACQ-6 score | — |
Countries
Australia, India, Poland, United Kingdom, United States of America
Contacts
Public ContactRashmi Chitgupi
PPD Pharmaceutical Development India Private Limited
Outcome results
None listed