A Phase 2 IV Gallium Study for Patients With Cystic Fibrosis (IGNITE Study)

This is a phase 2, multi-center, randomized, placebo-controlled trial in adults with CF chronically infected with P. aeruginosa. The study will evaluate the safety and clinical efficacy of a five day infusion of IV gallium nitrate (IV gallium). The purpose of this study is to assess the efficacy of IV gallium to improve pulmonary function as measured by a 5% or greater relative improvement in forced expiratory volume in one second (FEV1) from baseline to Day 28.

Inclusion criteria

• Greater than or equal to 18 years of age at Screening
• Documented chronic colonization with P. aeruginosa defined as dentification in two sputum or oropharyngeal cultures within the year prior to Day 1
• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

• sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)
• two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
• Abnormal nasal potential difference (NPD; change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)
• FEV1 ≥ 25 % of predicted value at Screening
• Able to expectorate sputum
• Serum liver function tests ≤ 2.5 x upper limit of normal at Screening
• Serum urea nitrogen (BUN) ≤ 1.5 x upper limit of normal at Screening
• Serum creatinine ≤ 2.0 mg/dl and ≤ 1.5 x upper limit of normal at Screening
• Hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/mm3, and white blood cells (WBC)

≥ 4,500/mm3 at Screening

• Ionized calcium ≥ lower limit of normal at Screening
• Written informed consent obtained from subject or subject's legal representative
• Able to communicate with the Investigator and comply with the requirements of the protocol
• If female and of childbearing potential, must have a negative pregnancy test on Day 1 prior to receiving study drug
• If female and of childbearing potential, is willing to use adequate contraception for the duration of the study through Visit 5, as determined by the investigator
• If male and able to father a child, is willing to use adequate contraception for the duration of the study through Visit 5, as determined by the investigator
• Clinically stable with no significant changes in health status within 14 days prior to Day 1

Exclusion criteria

• Use of inhaled antibiotics within seven days prior to Day 1
• Unable or unwilling to withhold use of chronic inhaled antibiotics through Day 28
• Use of intravenous, inhaled, or oral antibiotics for an acute indication within 14 days prior to Day 1
• Use of bisphosphonates within seven days prior to Day 1
• History of osteoporosis (defined as the most recent dexa scan with a T-score ≤ -2.5 with the dexa scan performed within the five years prior to Screening)
• Lactating female
• Known sensitivity to gallium