A Phase 1b, Multi-center Study of IV Gallium Nitrate in Patients with Cystic Fibrosis who are colonized with Nontuberculosis Mycobacterium (The ABATE Study).

一项针对非结核分枝杆菌定植的囊性纤维化患者静脉注射硝酸镓的 1b 期多中心研究（ABATE 研究）。

• 批准号: 10237132
• 负责人: Christopher Hooper Goss
• 金额: $ 71.64万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10237132
• 关键词: Phase; 1b; Multi; center; Study

Project Summary: Nontuberculous Mycobacteria (NTM) infection in cystic fibrosis (CF) is common, particularly Mycobacterium avium complex (MAC) and M. abscessus complex and appears to be increasing in prevalence. New approaches are needed as current drug regimens involve prolonged administration of drugs with significant toxicity and rates of treatment failure are high. Despite prolonged courses of multidrug therapy, effective cure for MAC lung disease is just under 60% in subjects without immune suppression or CF. In regard to M. abscessus complex, treatment response has been variable. M. abscessus ssp. massiliense demonstrated a better treatment response with more sustained negative cultures compared to M. abscessus ssp. abscessus (88 vs 25%) in non-CF disease. Thus, novel treatments are needed to improve clinical outcomes. While still controversial, recent evidence supporting patient to patient spread of M. abscessus complex in CF centers raises the urgency of development of better treatments in CF. We propose to exploit the iron vulnerability of both MAC and M. abscessus complex by using the metal gallium as a "Trojan horse" to disrupt iron metabolism. Gallium has a nearly identical ionic radius as Fe, and some bacterial uptake systems are unable to distinguish gallium from iron. Gallium disrupts iron-dependent processes because Ga3+ cannot be reduced in physiological conditions, and iron's biological functions involves redox cycling. Thus, gallium incorporation into iron-containing proteins disrupts their functioning. Previous work by our group and others found that gallium compounds had antibacterial activity against a number of human pathogens including Pseudomonas aeruginosa, Fransella tulerensis, Acinetobacter baumanai, Klebsiella pneumoniae, and other important pathogens including MAC and M. abscessus complex. Our prior trials (phase 1b and 2b) in CF patients infected with P. aeruginosa demonstrated that a single course of IV gallium was safe and showed evidence of efficacy. Here we propose a phase 1b open label phase 1b bridging study to assess the safety and pharmacokinetics of two sequential 5-day infusions of gallium nitrate in adults with CF who are infected with either MAC and M. abscessus complex at a dose of 200 mg/m2/day. We will also assess for preliminary microbiologic effect using the study population and a contemporary control population enrolled in a parent observational PREDICT trial (PRospective Evaluation of NTM Disease In CysTic Fibrosis; NCT02073409), a 10 center observational study of NTM in CF funded by the US CF Foundation.

项目总结:

项目成果

Lung function decline is mitigated following liver transplantation in people with cystic fibrosis: A retrospective cohort study.

囊性纤维化患者肝移植后肺功能下降得到缓解：一项回顾性队列研究。

• DOI: 10.1097/lvt.0000000000000232
• 发表时间: 2024
• 期刊: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
• 作者: Albaiz,FaisalA;Ramos,KathleenJ;Sykes,Jenna;Stanojevic,Sanja;Ma,Xiayi;Quon,BradleyS;Marshall,BruceC;Cromwell,ElizabethA;Ostrenga,JoshuaS;Faro,Albert;Elbert,Alexander;Goss,ChristopherH;Stephenson,AnneL
• 通讯作者: Stephenson,AnneL

Variability in azithromycin practices among lung transplant providers in the International Society for Heart and Lung Transplantation Community.

• DOI: 10.1016/j.healun.2021.10.008
• 发表时间: 2022-01
• 期刊: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
• 作者: Kapnadak SG;Morrell ED;Wai TH;Goss CH;Shah PD;Merlo CA;Hachem RR;Ramos KJ
• 通讯作者: Ramos KJ

The effect of oral and intravenous antimicrobials on pulmonary exacerbation recovery in cystic fibrosis.

• DOI: 10.1016/j.jcf.2021.02.012
• 发表时间: 2021-11
• 期刊: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
• 作者: VanDevanter EJ;Heltshe SL;Skalland M;Lechtzin N;Nichols D;Goss CH
• 通讯作者: Goss CH

COVID-19 outcomes in people with cystic fibrosis.

• DOI: 10.1097/mcp.0000000000000823
• 发表时间: 2021-11-01
• 期刊: Current opinion in pulmonary medicine
• 影响因子: 3.3
• 作者: Burgel PR;Goss C
• 通讯作者: Goss C

The impact of SARS-CoV-2 on the cystic fibrosis foundation therapeutics development network.

• DOI: 10.1016/j.jcf.2020.12.007
• 发表时间: 2021-03
• 期刊: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
• 作者: Pearson K;Mayer-Hamblett N;Goss CH;Retsch-Bogart GZ;VanDalfsen JM;Burks P;Rosenbluth D;Clancy JP;Hoffman A;Nichols DP
• 通讯作者: Nichols DP