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

Study Description

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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

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Gallium nitrate; Drug: Normal Saline	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	120 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Multi-Center, Randomized, Placebo-Controlled Study of IV Gallium Nitrate in Patients With Cystic Fibrosis (IGNITE Study)
Actual Study Start Date :	March 2016
Actual Primary Completion Date :	February 1, 2018
Actual Study Completion Date :	February 1, 2018

Arms and Interventions

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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 Name: 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 Name: Sodium Chloride, NS

Outcome Measures

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Primary Outcome Measures :

1. Improvement in pulmonary function as measured by a 5% or greater relative improvement in forced expiratory volume in one second (FEV1). [ 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 Outcome Measures :

1. Safety and tolerability of IV gallium, as measured by incidence of adverse events (AEs), changes in clinical safety labs, and hospitalizations. [ Time Frame: Day 1 to Day 56 ]
   Difference between treatment groups in safety parameters including the incidence of adverse events (AEs), changes in clinical safety labs, and hospitalizations.
2. Improvement in measures of lung function including relative change in FEV1, absolute change in FEV1, and forced vital capacity (FVC). [ Time Frame: Day 1 to Day 56 ]
   Improvement in lung function as measured by relative change in FEV1, absolute change in FEV1, and forced vital capacity (FVC), measured by difference between treatment groups in the change in pulmonary function parameters .
3. Reduction of P. aeruginosa in the lungs of CF patients based on quantitative cultures of sputum. [ Time Frame: Day 1 to Day 56 ]
   Reduction of P. aeruginosa sputum density in the lungs of CF patients based difference between treatment groups', based on quantitative cultures.
4. Improvement of respiratory symptoms as measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS). [ Time Frame: Day 1 to Day 56 ]
   Improvement in respiratory symptoms as measured by the difference between treatment groups in the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS).
5. Sputum and blood PK profile of IV gallium [ Time Frame: Day 1 - Day 56 ]
   Sputum and blood PK profile of IV gallium measured by the determination of the steady state concentration (Css) and elimination half life (t1/2β ) in those subjects receiving IV gallium.
6. Rate of acquired resistance of P. aeruginosa to gallium. [ Time Frame: Day 1 to Day 56 ]
   Rate of acquired resistance of P. aeruginosa to gallium, measured by the difference between treatment groups in the emergence of other CF pathogens, including gallium-resistant P. aeruginosa.
7. Anti-inflammatory properties of IV gallium [ Time Frame: Day 1 to Day 56 ]
   Difference between treatment groups in the change in blood inflammatory markers.
8. Reduction in the use of antibiotics for an acute indication. [ Time Frame: Day 1 to Day 56 ]
   Reduction in the use of antibiotics for an acute indication measured by the difference between treatment groups in the rate of antibiotic usage including IV, oral, and inhaled for an acute indication.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Sponsors and Collaborators

University of Washington

Cystic Fibrosis Foundation

Investigators

Principal Investigator:	Christopher H Goss, MD	University of Washington

More Information

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Responsible Party:	Chris Goss, Professor, Medicine/Pulmonary & Critical Care Medicine, University of Washington
ClinicalTrials.gov Identifier:	NCT02354859 History of Changes
Other Study ID Numbers:	STUDY00002609; 2R01FD003704-03A1 ( U.S. FDA Grant/Contract )
First Posted:	February 3, 2015
Last Update Posted:	May 21, 2018
Last Verified:	May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
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.

Keywords provided by Chris Goss, University of Washington:

Cystic Fibrosis; Gallium Nitrate; IV Gallium; Pseudomonas aeruginosa

Additional relevant MeSH terms:

Fibrosis; Cystic Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases	Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Gallium nitrate; Antineoplastic Agents