A Phase 2 IV Gallium Study for Patients With Cystic Fibrosis (IGNITE Study)

Phase 2

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: Normal Saline
Drug: Gallium nitrate

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

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:
1. sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)
2. two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
3. 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

Exclusion Criteria

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): AL Adult Birmingham / The Children's Hospital Atlanta
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Birmingham, Alabama, United States
UC San Diego Medical Center
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La Jolla, California, United States
Denver Adult / National Jewish Health
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Denver, Colorado, United States
Shands Hospital
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Gainesville, Florida, United States
Jackson Memorial Hospital; University of Miami Hospital; University of Miami Hospital and Clinics
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Miami, Florida, United States
Atlanta Emory Adult / Emory University Hospital
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Atlanta, Georgia, United States
Chicago Northwestern Adult / Northwestern Memorial Hospital
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Chicago, Illinois, United States
Iowa City University of Iowa Adult / University of Iowa Hospitals & Clinics
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Iowa City, Iowa, United States
Lexington, KY Adult / University of Kentucky Chandler Medical Center
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Lexington, Kentucky, United States
Portland, ME Adult
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Portland, Maine, United States
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AL Adult Birmingham / The Children's Hospital Atlanta
🇺🇸Birmingham, Alabama, United States