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

Nontuberculous Mycobacterium Infection Clinical Trial

— ABATE  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04294043
• Other study ID #: ABATE-IP-18
• Secondary ID: R01FD006848
• Status: Recruiting
• Phase: Phase 1
• Start date: June 17, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: January 2024
• Source: Seattle Children's Hospital
• Contact: Natallia Cameron
• Phone: 206-884-7550
• Email: Natallia.Cameron[@]seattlechildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 Office of Orphan Products Development (OOPD)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 30, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 bronchoalveolar lavage (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. forced expiratory volume at one second (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., cystic fibrosis transmembrane conductance regulator (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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Mycobacterium Infections
• Mycobacterium Infections, Nontuberculous
• Nontuberculous Mycobacterium Infection

Intervention

Drug:
• Gallium nitrate
Study subjects will receive an infusion of gallium nitrate.

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	The Minnesota Cystic Fibrosis Center	Minneapolis	Minnesota
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Chris Goss	Cystic Fibrosis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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