Pilot Trial of Inhaled Molgramostim in Non-tuberculous Mycobacterial (NTM) Infection

Inclusion Criteria

• History of chronic pulmonary infection with MAC or M. abscessus (defined as at least 2 documented positive sputum cultures in the prior 2 years, of which at least one was obtained in the 6 months prior to Screening).
• Subject fulfills one of the following criteria:
• Subjects who remain sputum culture positive while currently on a multidrug NTM guideline based antimycobacterial regimen, which has been ongoing for at least 6 months prior to the Baseline Visit
• Subjects who remain sputum culture positive but have either stopped a multidrug NTM guideline based antimycobacterial regimen at least 28 days prior to Screening due to lack of response or intolerance, or never started such treatment.
• Ability to produce at least 2 mL of sputum or be willing to undergo an induction that produces at least 2 mL of sputum for clinical evaluation.
• Female or male ≥18 years of age.
• Females who have been post-menopausal for more than 1 year or females of childbearing potential after a confirmed menstrual period using a highly efficient method of contraception (i.e. a method with less than 1% failure rate such as combined hormonal contraception, progesterone-only hormonal contraception, intrauterine device, intrauterine hormone- releasing system, bilateral tubal occlusion, vasectomized partner, sexual abstinence), during and until thirty (30) days after last dose of trial treatment. Females of childbearing potential must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at dosing at Baseline (Visit 2) and must not be lactating.
• Males agreeing to use condoms during and until thirty (30) days after last dose of medication, or males having a female partner who is using adequate contraception as described above.
• Willing and able to provide signed informed consent.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures specified in the protocol as judged by the investigator

Exclusion Criteria

• Subjects diagnosed with cystic fibrosis.
• Prior therapy with inhaled or systemic GM-CSF.
• Subjects with hemoptysis of ≥60 mL in a 24 hour period within 4 weeks prior to Screening.
• Concurrent disease with a life expectancy of less than 6 months.
• History of, or present, myeloproliferative disease, leukemia or other hematological malignancy.
• Active pulmonary malignancy (primary or metastatic); or any malignancy requiring chemotherapy or radiation therapy within one year prior to Screening or anticipated during the study period.
• Active allergic bronchopulmonary mycosis or connective tissue disease, inflammatory bowel disease or other autoimmune disorder requiring therapy associated with significant immunosuppression, such as systemic corticosteroids at a dose equivalent of 10 mg/day or more of prednisolone, within 3 months prior to Screening or anticipated during the study period.
• Pulmonary tuberculosis requiring treatment or treated within 2 years prior to Screening.
• HIV infection or other disease associated with significant immunodeficiency.
• History of lung transplantation.
• Any change in chronic NTM multi-drug antimycobacterial regimen within 28 days prior to Screening.
• Treatment with any investigational medicinal product within 3 months of Screening.
• Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product
• Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial.