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

• ClinicalTrials.gov Identifier: NCT04294043
• Recruitment Status: Recruiting
• First Posted: March 3, 2020
• Last Update Posted: January 12, 2023
• Sponsor: Chris Goss
• Collaborator: Cystic Fibrosis Foundation
• Information provided by (Responsible Party): Chris Goss, Seattle Children's Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Nontuberculous Mycobacterium Infection	Drug: Gallium nitrate	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: June 17, 2021
• Estimated Primary Completion Date: September 30, 2023
• Estimated Study Completion Date: June 30, 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: Infusion of IV Gallium; 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; Study subjects will receive an infusion of gallium nitrate.; Other Names: Ga; GaN3O9; IV gallium; ganite

Outcome Measures

Primary Outcome Measures :

1. Adverse Events of Special Interest [ Time Frame: Baseline to Day 57 ]
   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.

Secondary Outcome Measures :

1. Clinically significant abnormal laboratory measures. (safety) [ Time Frame: Baseline to Day 57 ]
   Proportion of patients experiencing clinically significant abnormal laboratory measures. Clinically significant abnormal laboratory measures are identified by the site investigator.
2. NTM clearance (efficacy) [ Time Frame: Day 6 to Day 111 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Written informed consent obtained from subject or subject's legal representative
2. Be willing and able to adhere to the study visit schedule and other protocol requirements
3. All sexes ≥ 18 years of age at Visit 1
4. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype.

5. 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:

   1. The two most recent NTM culture results from sputum or BAL taken at least 28 days apart are positive.

      OR

   2. 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.
6. 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
7. FEV1 ≥ 25 % of predicted value at Screening
8. Able to expectorate sputum
9. Clinically stable with no significant changes in health status within 7 days prior to Day 1
10. Enrolled in the CFF Patient Registry (CFF PR)
11. Willing to discontinue chronic azithromycin use for the duration of the study

Exclusion Criteria:

1. 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)
2. History of solid organ or hematological transplantation
3. Use of bisphosphonates within 7 days prior to Day 1
4. Known sensitivity to gallium
5. Use of any investigational drug and/or participated in any interventional clinical trial within 28 days prior to Day 1
6. 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)
7. Undergoing treatment for NTM disease or anticipate beginning treatment within 3 months
8. Current diagnosis of osteoporosis

9. 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
10. For people able to father a child: unwilling to use adequate contraception (as determined by the investigator) during the study
11. 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
12. New initiation of chronic therapy (e.g., CFTR modulators, ibuprofen, azithromycin, inhaled tobramycin, Cayston, etc.) within 28 days prior to Visit 1 (Day 1)
13. Use of azithromycin within 14 days prior to the screening visit.

Contacts and Locations

Contacts

Contact: Natallia Cameron; 206-884-7550; Natallia.Cameron@seattlechildrens.org

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35294

Contact: Justin Wade jdwade@uabmc.edu

United States, Colorado

National Jewish Health; Recruiting

Denver, Colorado, United States, 80206

Contact: Alix Wilson wilsona@njhealth.org

United States, Maryland

Johns Hopkins University; Recruiting

Baltimore, Maryland, United States, 21205

Contact: Britany Zeglin bzeglin1@jhmi.edu

United States, Ohio

Nationwide Children's Hospital; Recruiting

Columbus, Ohio, United States, 43205

Contact: Diana Gilmore diana.gilmore@nationwidechildrens.org

United States, Pennsylvania

University of Pittsburgh Medical Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15224

Contact: Elizabeth Hartigan elizabeth.hartigan@chp.edu

United States, South Carolina

Medical University of South Carolina; Recruiting

Charleston, South Carolina, United States, 29425

Contact: Ashley Warden jonesash@musc.edu

United States, Texas

University of Texas Southwestern; Recruiting

Dallas, Texas, United States, 75390

Contact: Ashley Keller Ashley.Keller@UTSouthwestern.edu

United States, Vermont

University of Vermont Medical Center; Recruiting

Burlington, Vermont, United States, 05401

Contact: Julie Sweet julie.sweet@uvmhealth.org

United States, Washington

University of Washington Medical Center; Recruiting

Seattle, Washington, United States, 98195

Contact: Teresa Gambol TGambol@medicine.washington.edu

Sponsors and Collaborators

Chris Goss

Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Christopher H. Goss, MD, MSc; University of Washington, Seattle Children's Hospital

More Information

• Responsible Party: Chris Goss, Professor of Medicine and Pediatrics, University of Washington, Seattle Children's Hospital
• ClinicalTrials.gov Identifier: NCT04294043
• Other Study ID Numbers: ABATE-IP-18; R01FD006848 ( U.S. FDA Grant/Contract )
• First Posted: March 3, 2020
• Last Update Posted: January 12, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Chris Goss, Seattle Children's Hospital:

Cystic Fibrosis; Gallium Nitrate; IV Gallium; Nontuberculous mycobacterium; NTM; Mycobacterium abscessus; mycobacterium avium

Additional relevant MeSH terms:

Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Gallium nitrate; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Antineoplastic Agents