IV Gallium Study for Patients With Cystic Fibrosis Who Have NTM (ABATE Study)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of two 5-day infusion cycles of IV gallium in adult patients with CF who are infected with NTM. Funding Source - FDA OOPD

Detailed Description
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This is a prospective, multicenter open-label study in adults with CF who are colonized with M. avium complex and/or M. abscessus complex. Subjects will receive two 5-day infusion cycles of IV gallium. The study will evaluate the safety and antimycobacterial effect of two 5-day infusions of IV gallium.

Official Title
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A Phase 1b, Multi-center Study of Intravenous (IV) Gallium Nitrate in Patients With Cystic Fibrosis (CF) Who Are Colonized With Nontuberculous Mycobacteria (NTM) (The ABATE Study)

Conditions
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Nontuberculous Mycobacterium Infection

Intervention / Treatment
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* Drug: Gallium nitrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained from subject or subject's legal representative Be willing and able to adhere to the study visit schedule and other protocol requirements All sexes ≥ 18 years of age at Visit 1 Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype. Documentation of persistently positive NTM culture results that are positive for the same species or sub-species (either M. avium complex, M. abscessus complex, or both M. avium and M. abscessus). Persistently positive cultures are those which meet ONE of the following criteria, after first ignoring any negative culture results that occur within 7 days of a positive culture: The two most recent NTM culture results from sputum or BAL taken at least 28 days apart are positive. OR At least one NTM culture result in the previous 4 months from sputum or BAL is positive. If there are four or more cultures in the last 12-months at least 3 out of the 4 most recent cultures must be positive for NTM. If there are three or fewer cultures in the past 12 months, then at least 2 of the 3 most recent cultures must be positive for NTM even if some of those cultures are more than 12 months ago. Current NTM species or subspecies has never been treated or previous treatment was associated with clearance of NTM and completed > 2 years prior to Day 1 FEV1 ≥ 25 % of predicted value at Screening Able to expectorate sputum Clinically stable with no significant changes in health status within 7 days prior to Day 1 Enrolled in the CFF Patient Registry (CFF PR) Willing to discontinue chronic azithromycin use for the duration of the study Exclusion Criteria: Any of the following abnormal lab values at screening: Hemoglobin <10g/dL Platelets <100,000/mm3 Absolute neutrophil count < 1500/mm3 Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) ≥3 x upper limit of normal Serum creatinine > 2.0 mg/dl and ≥1.5 x upper limit of normal Ionized calcium ≤ lower limit of normal (only performed if total calcium is ≤ lower limit of normal) History of solid organ or hematological transplantation Use of bisphosphonates within 7 days prior to Day 1 Known sensitivity to gallium Use of any investigational drug and/or participated in any interventional clinical trial within 28 days prior to Day 1 In the opinion of the Investigator, features of active NTM disease are present (e.g., clinical worsening is likely due to NTM disease despite definitive treatment of co-pathogens and/or acute exacerbations) Undergoing treatment for NTM disease or anticipate beginning treatment within 3 months Current diagnosis of osteoporosis For people of childbearing potential: Positive pregnancy test at Visit 1 or Lactating or Unwilling to practice a medically acceptable form of contraception (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent), unless surgically sterilized or postmenopausal during the study For people able to father a child: unwilling to use adequate contraception (as determined by the investigator) during the study Has any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives New initiation of chronic therapy (e.g., CFTR modulators, ibuprofen, azithromycin, inhaled tobramycin, Cayston, etc.) within 28 days prior to Visit 1 (Day 1) Use of azithromycin within 14 days prior to the screening visit.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infusion of IV Gallium<br>Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device using an ambulatory infusion pump infused over 24 hours for 5 sequential days for each cycle. There is a maximum of 2 cycles. | Drug: Gallium nitrate<br>* Study subjects will receive an infusion of gallium nitrate.<br>* Other names: ganite;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events of Special Interest | Proportion of patients experiencing one or more Adverse Events of Special Interest (AESI). AESIs include the occurrence of either (1) a serious adverse event (SAE) of grade 3 or higher including hospitalizations or (2) study drug discontinuation because of an AE. | Baseline to Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically significant abnormal laboratory measures. (safety) | Proportion of patients experiencing clinically significant abnormal laboratory measures. Clinically significant abnormal laboratory measures are identified by the site investigator. | Baseline to Day 57 | 
| NTM clearance (efficacy) | Proportion of subjects who were NTM culture positive at baseline and have at least 2 sequential negative NTM cultures between visits 2 (Day 6) and 7 (Day 111). Those negative cultures must be at least 2 weeks apart. | Day 6 to Day 111 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Gallium Nitrate, IV Gallium, Nontuberculous mycobacterium, NTM, Mycobacterium abscessus, mycobacterium avium