Phase 2 Study of Intravenous Gallium Nitrate in the Treatment of Cystic Fibrosis

描述（由申请人提供）：

DESCRIPTION (provided by applicant): A novel anti-infective approach is to exploit stresses already imposed on invading organisms in vivo. Iron (Fe) metabolism is a key vulnerability of infecting bacteria because organisms require iron for growth. The applicant proposed that a strategy using the metal gallium (Ga) to disrupt bacterial iron metabolism holds promise as an antimicrobial approach. Due to its chemical similarity to iron, the applicants state that gallium can substitute for iron in many biologic systems and inhibit iron-dependent processes. The applicant has complied data to show that gallium kills the opportunistic pathogen Pseudomonas aeruginosa (including antibiotic resistant strains), is active against biofilms, and treats 3 different models of Pseudomonas aeruginosa infections. These data, the fact that gallium nitrate (trade name, Ganite) is FDA approved for intravenous (IV) administration, and the dearth of new antibiotics in development indicate to the applicant that gallium could be a promising new therapeutic for Pseudomonas aeruginosa infections. An initial Phase 1b study in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa indicated to the applicant that IV gallium appeared to be safe, well tolerated, has a good pharmacokinetic profile, and is associated with a clinically meaningful improvement in lung function 14 days and 28 days after the start of a 5 day infusion of IV gallium. The applicant proposes a proof of concept Phase 2 clinical trial to confirm the prior findings of efficacy and provide further data regarding the safety and pharmacokinetics of IV gallium in cystic fibrosis subjects infected with Pseudomonas aeruginosa. The Specific Aims of the study are to: 1) assess the pulmonary function response rate at day 28 in cystic fibrosis patients receiving a 5-day continuous IV gallium and placebo; and 2) to assess the safety and pharmacokinetics of a 5 day continuous IV infusions of gallium in adult cystic fibrosis subjects compared to placebo.