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

Overview

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

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 1, 2018

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.

Interventions

  • Drug: Gallium nitrate
    • Study subjects will receive an infusion of either placebo or gallium nitrate.
  • Drug: Normal Saline
    • Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.

Arms, Groups and Cohorts

  • Active Comparator: 5 day of infusion of 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.
  • Placebo Comparator: 5 day of infusion of normal saline
    • Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga

Clinical Trial Outcome Measures

Primary Measures

  • Number of Participants With 5% or Greater Relative Change in FEV1 (Liters) From Baseline to Day 28
    • Time Frame: 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 Measures

  • Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
    • Time Frame: 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.
  • Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
    • Time Frame: 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
    • Time Frame: Day 1 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
    • Time Frame: 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.
  • 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
    • Time Frame: 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Washington
  • Collaborator
    • Cystic Fibrosis Foundation
  • Provider of Information About this Clinical Study
    • Principal Investigator: Chris Goss, Professor, Medicine/Pulmonary & Critical Care Medicine – University of Washington
  • Overall Official(s)
    • Christopher H Goss, MD, Principal Investigator, University of Washington

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