A Pilot Study to Assess the Effect of Intermittent iNO on the Treatment of NTM Lung Infection in CF and Non-CF Patients

A Pilot Study to Assess the Effect of Intermittent Inhaled Nitric Oxide on the Treatment of Nontuberculous Mycobacteria (NTM) Lung Infection in Cystic Fibrosis and Non-Cystic Fibrosis Patients

The purpose of this open-label, multicenter, non-randomized, pilot study is to assess the safety of high dose intermittent iNO for treatment of NTM infection in CF and non-CF patients.

The study will include 20 patients from up to four clinical sites in Australia. The overall treatment plan includes 2 weeks of inhalation treatments (intensive phase) of iNO four times per day at 4.5-hour intervals followed by 10 weeks of inhalation treatments (maintenance phase) at the maximum tolerated dose (a maximum of 250 ppm NO) inhaled twice daily.

Inclusion Criteria:

• Subjects diagnosed with refractory NTM (MAC or MAbs) pulmonary infection
• CF and Non-CF patients

Exclusion Criteria:

• Diagnosis of methemoglobinemia or MetHb ≥2% at screening; treatment with any drug known to increase MetHb; known or suspected hemoglobinopathy.
• History of or current myeloproliferative disease, leukemia or other hematological malignancy; known or suspected immunodeficiency disease.
• Subjects with advanced cardiovascular disease or CHF
• Use of an investigational drug during the 30 days prior to enrollment.
• History of frequent epistaxis (>1 episode/month); significant hemoptysis (during the 30 days prior to enrollment.
• Subject on non-constant dose of systemic steroids within 30 days prior to enrollment; subjects on constant systemic steroids if the daily dose is higher than 10 mg/d prednisolone or equivalent.
• Active pulmonary malignancy (primary or metastatic) or any malignancy; history of lung transplantation.
• Pulmonary tuberculosis requiring treatment or treated within 2 years prior to screening.
• Uncontrolled hypertension within 3 months prior to or at screening
• Diagnosis of significant pulmonary hypertension indicated on echocardiogram at screening
• Clinically significant renal or liver laboratory abnormalities
• History of daily, continuous oxygen supplementation.
• Women of childbearing potential - pregnant or breastfeeding, or not on medically acceptable double methods of contraception from enrollment until Day 84.
• Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study.
• Patient receiving drugs that have a contraindication with NO