A Phase 2 IV Gallium Study for Patients With Cystic Fibrosis (IGNITE Study)
- Registration Number
- NCT02354859
- Lead Sponsor
- University of Washington
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 119
-
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
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Able to communicate with the Investigator and comply with the requirements of the protocol
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If female and of childbearing potential, must have a negative pregnancy test on Day 1 prior to receiving study drug
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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
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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
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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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 5 day of infusion of normal saline Normal Saline Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga 5 day of infusion of gallium nitrate Gallium nitrate 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.
- Primary Outcome Measures
Name Time Method Number of Participants With 5% or Greater Relative Change in FEV1 (Liters) From Baseline to Day 28 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
Name Time Method Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 to Day 56 Rate is defined as the number of events per participant follow-up week.
Relative Change in FEV1 (Liters) From Baseline to Day 56 Day 1 to Day 56 Difference between treatment groups in the relative change in FEV1 (liters) from Baseline to Day 56
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 to Day 56 Incidence is defined as the number and percentage of participants with at least one event over the 56 day follow-up period.
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 Day 1 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.
Absolute Change in P. Aeruginosa Sputum Density (log10 (CFU)) From Baseline to Day 56 Day 1 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.
Trial Locations
- Locations (23)
Jackson Memorial Hospital; University of Miami Hospital; University of Miami Hospital and Clinics
🇺🇸Miami, Florida, United States
AL Adult Birmingham / The Children's Hospital Atlanta
🇺🇸Birmingham, Alabama, United States
Columbus CC and Peds / Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Pittsburgh Adult, Children's Hospital of Pittsburgh UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Lexington, KY Adult / University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Minneapolis CC and Adult / University of Minnesota Medical Center, Fairview
🇺🇸Minneapolis, Minnesota, United States
UC San Diego Medical Center
🇺🇸La Jolla, California, United States
Shands Hospital
🇺🇸Gainesville, Florida, United States
Denver Adult / National Jewish Health
🇺🇸Denver, Colorado, United States
Boston CHB Adult / Boston Children's Hospital (BCH)
🇺🇸Boston, Massachusetts, United States
Lebanon, NH Dartmouth-Hitchcock CC and Adult / Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Portland, ME Adult
🇺🇸Portland, Maine, United States
Omaha Adult / The Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Atlanta Emory Adult / Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Chicago Northwestern Adult / Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Iowa City University of Iowa Adult / University of Iowa Hospitals & Clinics
🇺🇸Iowa City, Iowa, United States
Baltimore Hopkins Adult / John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Cleveland CC and Peds, Hospital of Cleveland
🇺🇸Cleveland, Ohio, United States
Toledo, OH CC and Peds / The Toledo Hospital; Toledo Children's Hospital
🇺🇸Toledo, Ohio, United States
Oklahoma City Adult / Presbyterian Hospital at OU Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
SC CC and Adult Charleston / MUSC
🇺🇸Charleston, South Carolina, United States
Salt Lake City Adult, Intermountain Cystic Fibrosis Center
🇺🇸Salt Lake City, Utah, United States
Seattle UW Adult / University of Washington Medical Center
🇺🇸Seattle, Washington, United States