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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2, Multi-Center, Randomized, Placebo-Controlled Study of IV Gallium Nitrate in Patients With Cystic Fibrosis (IGNITE Study)

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Gallium nitrate
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5 day of infusion of gallium nitrate<br>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. | Drug: Gallium nitrate<br>* Study subjects will receive an infusion of either placebo or gallium nitrate.<br>* Other names: Ga, GaN3O9;|
| Placebo Comparator: 5 day of infusion of normal saline<br>Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga | Drug: Normal Saline<br>* Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.<br>* Other names: Sodium Chloride, NS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 to Day 56 | 
| Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) | Rate is defined as the number of events per participant follow-up week. | Day 1 to Day 56 | 
| 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 | Day 1 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. | Day 1 to Day 56 | 
| 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. | Day 1 to Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis, Gallium Nitrate, IV Gallium, Pseudomonas aeruginosa