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

Sponsor

Chris Goss (Other)

Overall Status

Recruiting

CT.gov ID

NCT04294043

Collaborator

Cystic Fibrosis Foundation (Other)

Enrollment

Locations

Arm

39.5

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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

Anticipated 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 :

Jun 17, 2021

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Sep 30, 2024

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

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:

GaN3O9

IV gallium

ganite

Outcome Measures

Primary Outcome Measures

Adverse Events of Special Interest [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

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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
Greater than or equal to 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 and one or more of the following criteria:

Sweat chloride ≥ 60 milliequivalent (mEq)/liter by quantitative pilocarpine iontophoresis test (QPIT)
Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Abnormal nasal potential difference (NPD) (change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)

Documentation of NTM culture positive defined as follows:

Two positive NTM culture results from sputum (or BAL) at least 28 days apart (these are the two qualifying positive cultures)
Both qualifying positive culture results include M. avium complex, M. abscessus complex, or both M. avium and M. abscessus
Both qualifying positive culture results include the same species or subspecies
No cultures negative for NTM since the first of the two qualifying positive culture results

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
Forced expiratory volume in 1 second (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 Cystic Fibrosis Foundation Patient Registry (CFFPR)
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
White blood cells (WBC) < 4,500/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 (greater than 21 days) within 28 days prior to the Enrollment Visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	National Jewish Health	Denver	Colorado	United States	80206
3	University of Florida	Gainesville	Florida	United States	32610
4	Johns Hopkins University	Baltimore	Maryland	United States	21205
5	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
6	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15224
7	Medical University of South Carolina	Charleston	South Carolina	United States	29425
8	University of Texas Southwestern	Dallas	Texas	United States	75390
9	University of Vermont Medical Center	Burlington	Vermont	United States	05401
10	University of Washington Medical Center	Seattle	Washington	United States	98195