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

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

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

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Gallium nitrate; Drug: Normal Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • AL Adult Birmingham / The Children's Hospital Atlanta
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • Denver Adult / National Jewish Health
  • Florida
    • Gainesville, Florida, United States, 32610
      • Shands Hospital
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital; University of Miami Hospital; University of Miami Hospital and Clinics
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Atlanta Emory Adult / Emory University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Chicago Northwestern Adult / Northwestern Memorial Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Iowa City University of Iowa Adult / University of Iowa Hospitals & Clinics
  • Kentucky
    • Lexington, Kentucky, United States, 40506-9983
      • Lexington, KY Adult / University of Kentucky Chandler Medical Center
  • Maine
    • Portland, Maine, United States, 04102
      • Portland, ME Adult
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Baltimore Hopkins Adult / John Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston CHB Adult / Boston Children's Hospital (BCH)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Minneapolis CC and Adult / University of Minnesota Medical Center, Fairview
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5300
      • Omaha Adult / The Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Lebanon, NH Dartmouth-Hitchcock CC and Adult / Dartmouth Hitchcock Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland CC and Peds, Hospital of Cleveland
    • Columbus, Ohio, United States, 43205
      • Columbus CC and Peds / Nationwide Children's Hospital
    • Toledo, Ohio, United States, 43606
      • Toledo, OH CC and Peds / The Toledo Hospital; Toledo Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma City Adult / Presbyterian Hospital at OU Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Pittsburgh Adult, Children's Hospital of Pittsburgh UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • SC CC and Adult Charleston / MUSC
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Salt Lake City Adult, Intermountain Cystic Fibrosis Center
  • Washington
    • Seattle, Washington, United States, 98195
      • Seattle UW Adult / University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Gallium nitrate; Study subjects will receive an infusion of either placebo or gallium nitrate.; Other Names: Ga, GaN3O9
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	Drug: Normal Saline; Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.; Other Names: Sodium Chloride, NS

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Christopher H Goss, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: February 2, 2015
• First Posted (Estimate): February 3, 2015

Study Record Updates

• Last Update Posted (Actual): March 21, 2019
• Last Update Submitted That Met QC Criteria: March 20, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Pseudomonas aeruginosa; Gallium Nitrate; IV Gallium
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Antineoplastic Agents; Calcium-Regulating Hormones and Agents; Gallium nitrate
• Other Study ID Numbers: STUDY00002609; 2R01FD003704-03A1 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.