Back to resultsA Phase 2 IV Gallium Study for Patients With Cystic Fibrosis (IGNITE Study)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gallium nitrate
Normal Saline
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, Gallium Nitrate, IV Gallium, Pseudomonas aeruginosa
Eligibility Criteria
Inclusion Criteria:
- Greater than or equal to 18 years of age at Screening
- Documented chronic colonization with P. aeruginosa defined as dentification in two sputum or oropharyngeal cultures within the year prior to Day 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 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)
- FEV1 ≥ 25 % of predicted value at Screening
- Able to expectorate sputum
- Serum liver function tests ≤ 2.5 x upper limit of normal at Screening
- Serum urea nitrogen (BUN) ≤ 1.5 x upper limit of normal at Screening
- Serum creatinine ≤ 2.0 mg/dl and ≤ 1.5 x upper limit of normal at Screening
Hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/mm3, and white blood cells (WBC)
≥ 4,500/mm3 at Screening
- Ionized calcium ≥ lower limit of normal at Screening
- Written informed consent obtained from subject or subject's legal representative
- Able to communicate with the Investigator and comply with the requirements of the protocol
- If female and of childbearing potential, must have a negative pregnancy test on Day 1 prior to receiving study drug
- If female and of childbearing potential, is willing to use adequate contraception for the duration of the study through Visit 5, as determined by the investigator
- If male and able to father a child, is willing to use adequate contraception for the duration of the study through Visit 5, as determined by the investigator
- Clinically stable with no significant changes in health status within 14 days prior to Day 1
Exclusion criteria:
- Use of inhaled antibiotics within seven days prior to Day 1
- Unable or unwilling to withhold use of chronic inhaled antibiotics through Day 28
- Use of intravenous, inhaled, or oral antibiotics for an acute indication within 14 days prior to Day 1
- Use of bisphosphonates within seven days prior to Day 1
- History of osteoporosis (defined as the most recent dexa scan with a T-score ≤ -2.5 with the dexa scan performed within the five years prior to Screening)
- Lactating female
- Known sensitivity to gallium
Sites / Locations
- AL Adult Birmingham / The Children's Hospital Atlanta
- UC San Diego Medical Center
- Denver Adult / National Jewish Health
- Shands Hospital
- Jackson Memorial Hospital; University of Miami Hospital; University of Miami Hospital and Clinics
- Atlanta Emory Adult / Emory University Hospital
- Chicago Northwestern Adult / Northwestern Memorial Hospital
- Iowa City University of Iowa Adult / University of Iowa Hospitals & Clinics
- Lexington, KY Adult / University of Kentucky Chandler Medical Center
- Portland, ME Adult
- Baltimore Hopkins Adult / John Hopkins Hospital
- Boston CHB Adult / Boston Children's Hospital (BCH)
- Minneapolis CC and Adult / University of Minnesota Medical Center, Fairview
- Omaha Adult / The Nebraska Medical Center
- Lebanon, NH Dartmouth-Hitchcock CC and Adult / Dartmouth Hitchcock Medical Center
- Cleveland CC and Peds, Hospital of Cleveland
- Columbus CC and Peds / Nationwide Children's Hospital
- Toledo, OH CC and Peds / The Toledo Hospital; Toledo Children's Hospital
- Oklahoma City Adult / Presbyterian Hospital at OU Medical Center
- Pittsburgh Adult, Children's Hospital of Pittsburgh UPMC
- SC CC and Adult Charleston / MUSC
- Salt Lake City Adult, Intermountain Cystic Fibrosis Center
- Seattle UW Adult / University of Washington Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
5 day of infusion of gallium nitrate
5 day of infusion of normal saline
Arm Description
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.
Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga
Outcomes
Primary Outcome Measures
Number of Participants With 5% or Greater Relative Change in FEV1 (Liters) From Baseline to Day 28
Difference between treatment groups in the proportion of subjects with 5% or greater relative change in FEV1 (liters) from baseline to Day 28.
Secondary Outcome Measures
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence is defined as the number and percentage of participants with at least one event over the 56 day follow-up period.
Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Rate is defined as the number of events per participant follow-up week.
Relative Change in FEV1 (Liters) From Baseline to Day 56
Difference between treatment groups in the relative change in FEV1 (liters) from Baseline to Day 56
Absolute Change in P. Aeruginosa Sputum Density (log10 (CFU)) From Baseline to Day 56
Difference between treatment groups in the absolute change in P. aeruginosa sputum density (log10 (CFU)) from Baseline to Day 56 based on quantitative cultures.
Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), From Baseline to Day 56
Difference between treatment groups in the absolute change in respiratory symptoms, as measured by the the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), from Baseline to Day 56. The Cystic Fibrosis Respiratory Symptoms Daily Diary asks a participant to state the extent of their 8 respiratory symptoms : difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.
Full Information
NCT ID
NCT02354859
First Posted
July 30, 2014
Last Updated
March 20, 2019
Sponsor
University of Washington
Collaborators
Cystic Fibrosis Foundation
1. Study Identification
Unique Protocol Identification Number
NCT02354859
Brief Title
A Phase 2 IV Gallium Study for Patients With Cystic Fibrosis (IGNITE Study)
Official Title
A Phase 2, Multi-Center, Randomized, Placebo-Controlled Study of IV Gallium Nitrate in Patients With Cystic Fibrosis (IGNITE Study)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
March 2016 (Actual)
Primary Completion Date
February 1, 2018 (Actual)
Study Completion Date
February 1, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
Cystic Fibrosis Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy of IV gallium to improve pulmonary function as measured by a 5% or greater relative improvement in forced expiratory volume in one second (FEV1) from baseline to Day 28.
Funding Source - FDA OOPD
Detailed Description
This is a phase 2, multi-center, randomized, placebo-controlled trial in adults with CF chronically infected with P. aeruginosa. The study will evaluate the safety and clinical efficacy of a five day infusion of IV gallium nitrate (IV gallium). The purpose of this study is to assess the efficacy of IV gallium to improve pulmonary function as measured by a 5% or greater relative improvement in forced expiratory volume in one second (FEV1) from baseline to Day 28.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Cystic Fibrosis, Gallium Nitrate, IV Gallium, Pseudomonas aeruginosa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
119 (Actual)
8. Arms, Groups, and Interventions
Arm Title
5 day of infusion of gallium nitrate
Arm Type
Active Comparator
Arm Description
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.
Arm Title
5 day of infusion of normal saline
Arm Type
Placebo Comparator
Arm Description
Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga
Intervention Type
Drug
Intervention Name(s)
Gallium nitrate
Other Intervention Name(s)
Ga, GaN3O9
Intervention Description
Study subjects will receive an infusion of either placebo or gallium nitrate.
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
Sodium Chloride, NS
Intervention Description
Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Primary Outcome Measure Information:
Title
Number of Participants With 5% or Greater Relative Change in FEV1 (Liters) From Baseline to Day 28
Description
Difference between treatment groups in the proportion of subjects with 5% or greater relative change in FEV1 (liters) from baseline to Day 28.
Time Frame
Baseline to Day 28
Secondary Outcome Measure Information:
Title
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Incidence is defined as the number and percentage of participants with at least one event over the 56 day follow-up period.
Time Frame
Day 1 to Day 56
Title
Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Rate is defined as the number of events per participant follow-up week.
Time Frame
Day 1 to Day 56
Title
Relative Change in FEV1 (Liters) From Baseline to Day 56
Description
Difference between treatment groups in the relative change in FEV1 (liters) from Baseline to Day 56
Time Frame
Day 1 to Day 56
Title
Absolute Change in P. Aeruginosa Sputum Density (log10 (CFU)) From Baseline to Day 56
Description
Difference between treatment groups in the absolute change in P. aeruginosa sputum density (log10 (CFU)) from Baseline to Day 56 based on quantitative cultures.
Time Frame
Day 1 to Day 56
Title
Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), From Baseline to Day 56
Description
Difference between treatment groups in the absolute change in respiratory symptoms, as measured by the the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), from Baseline to Day 56. The Cystic Fibrosis Respiratory Symptoms Daily Diary asks a participant to state the extent of their 8 respiratory symptoms : difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.
Time Frame
Day 1 to Day 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Greater than or equal to 18 years of age at Screening
Documented chronic colonization with P. aeruginosa defined as dentification in two sputum or oropharyngeal cultures within the year prior to Day 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 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)
FEV1 ≥ 25 % of predicted value at Screening
Able to expectorate sputum
Serum liver function tests ≤ 2.5 x upper limit of normal at Screening
Serum urea nitrogen (BUN) ≤ 1.5 x upper limit of normal at Screening
Serum creatinine ≤ 2.0 mg/dl and ≤ 1.5 x upper limit of normal at Screening
Hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/mm3, and white blood cells (WBC)
≥ 4,500/mm3 at Screening
Ionized calcium ≥ lower limit of normal at Screening
Written informed consent obtained from subject or subject's legal representative
Able to communicate with the Investigator and comply with the requirements of the protocol
If female and of childbearing potential, must have a negative pregnancy test on Day 1 prior to receiving study drug
If female and of childbearing potential, is willing to use adequate contraception for the duration of the study through Visit 5, as determined by the investigator
If male and able to father a child, is willing to use adequate contraception for the duration of the study through Visit 5, as determined by the investigator
Clinically stable with no significant changes in health status within 14 days prior to Day 1
Exclusion criteria:
Use of inhaled antibiotics within seven days prior to Day 1
Unable or unwilling to withhold use of chronic inhaled antibiotics through Day 28
Use of intravenous, inhaled, or oral antibiotics for an acute indication within 14 days prior to Day 1
Use of bisphosphonates within seven days prior to Day 1
History of osteoporosis (defined as the most recent dexa scan with a T-score ≤ -2.5 with the dexa scan performed within the five years prior to Screening)
Lactating female
Known sensitivity to gallium
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher H Goss, MD
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
AL Adult Birmingham / The Children's Hospital Atlanta
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
UC San Diego Medical Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Denver Adult / National Jewish Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Shands Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Jackson Memorial Hospital; University of Miami Hospital; University of Miami Hospital and Clinics
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Atlanta Emory Adult / Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Chicago Northwestern Adult / Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Iowa City University of Iowa Adult / University of Iowa Hospitals & Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Lexington, KY Adult / University of Kentucky Chandler Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40506-9983
Country
United States
Facility Name
Portland, ME Adult
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Baltimore Hopkins Adult / John Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Boston CHB Adult / Boston Children's Hospital (BCH)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Minneapolis CC and Adult / University of Minnesota Medical Center, Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Omaha Adult / The Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-5300
Country
United States
Facility Name
Lebanon, NH Dartmouth-Hitchcock CC and Adult / Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Cleveland CC and Peds, Hospital of Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Columbus CC and Peds / Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Toledo, OH CC and Peds / The Toledo Hospital; Toledo Children's Hospital
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43606
Country
United States
Facility Name
Oklahoma City Adult / Presbyterian Hospital at OU Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Pittsburgh Adult, Children's Hospital of Pittsburgh UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
SC CC and Adult Charleston / MUSC
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Salt Lake City Adult, Intermountain Cystic Fibrosis Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Seattle UW Adult / University of Washington Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Once the study is complete and the primary paper is published, de-identified data will be available from the Cystic Fibrosis Therapeutics Development Network Coordinating Center upon approval of a formal data request.
Learn more about this trial
A Phase 2 IV Gallium Study for Patients With Cystic Fibrosis (IGNITE Study)
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