IV Gallium Study for Patients With Cystic Fibrosis Who Have NTM (ABATE Study)
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 |
---|---|---|
|
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
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:
|
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
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 |
Sponsors and Collaborators
- Chris Goss
- Cystic Fibrosis Foundation
Investigators
- Principal Investigator: Christopher H. Goss, MD, MSc, University of Washington, Seattle Children's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ABATE-IP-18
- R01FD006848