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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02354859
• Other study ID #: STUDY00002609
• Secondary ID: 2R01FD003704-03A
• Status: Completed
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: February 1, 2018

Study information

• Verified date: March 2019
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: February 1, 2018
• Est. primary completion date: February 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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

Locations

Country	Name	City	State
United States	Atlanta Emory Adult / Emory University Hospital	Atlanta	Georgia
United States	Baltimore Hopkins Adult / John Hopkins Hospital	Baltimore	Maryland
United States	AL Adult Birmingham / The Children's Hospital Atlanta	Birmingham	Alabama
United States	Boston CHB Adult / Boston Children's Hospital (BCH)	Boston	Massachusetts
United States	SC CC and Adult Charleston / MUSC	Charleston	South Carolina
United States	Chicago Northwestern Adult / Northwestern Memorial Hospital	Chicago	Illinois
United States	Cleveland CC and Peds, Hospital of Cleveland	Cleveland	Ohio
United States	Columbus CC and Peds / Nationwide Children's Hospital	Columbus	Ohio
United States	Denver Adult / National Jewish Health	Denver	Colorado
United States	Shands Hospital	Gainesville	Florida
United States	Iowa City University of Iowa Adult / University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	UC San Diego Medical Center	La Jolla	California
United States	Lebanon, NH Dartmouth-Hitchcock CC and Adult / Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Lexington, KY Adult / University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Jackson Memorial Hospital; University of Miami Hospital; University of Miami Hospital and Clinics	Miami	Florida
United States	Minneapolis CC and Adult / University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota
United States	Oklahoma City Adult / Presbyterian Hospital at OU Medical Center	Oklahoma City	Oklahoma
United States	Omaha Adult / The Nebraska Medical Center	Omaha	Nebraska
United States	Pittsburgh Adult, Children's Hospital of Pittsburgh UPMC	Pittsburgh	Pennsylvania
United States	Portland, ME Adult	Portland	Maine
United States	Salt Lake City Adult, Intermountain Cystic Fibrosis Center	Salt Lake City	Utah
United States	Seattle UW Adult / University of Washington Medical Center	Seattle	Washington
United States	Toledo, OH CC and Peds / The Toledo Hospital; Toledo Children's Hospital	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	Cystic Fibrosis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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