Trial Outcomes & Findings for IL-17 Neutrophils in CF Lung Inflammation (NCT NCT02025829)

Results Overview

In the Exacerbation/IV Antibiotics Cohort--Subjects will serve as their own controls. The percentage of neutrophils (in sputum) positive for IL-17 was determined by flow cytometry for each subject at the beginning and end of treatment for a pulmonary exacerbation. Sputum IL-17 neutrophil counts will be compared to the change in lung function (FEV1) as determined by spirometry (American Thoracic Society standards).

Recruitment status

COMPLETED

Target enrollment

14 participants

Primary outcome timeframe

End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbation

Results posted on

2019-02-15

Participant Flow

Participant milestones

Participant milestones
Measure	Clinically Stable Patients with cystic fibrosis and are clinically stable, 10 subjects with one copy of F508del and 4 subjects with at least one copy of G551D	Exacerbation Patients with cystic fibrosis admitted for treatment of a pulmonary exacerbation with IV antibiotics, 10 subjects with one copy of F508del
Overall Study STARTED	3	11
Overall Study COMPLETED	3	11
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

IL-17 Neutrophils in CF Lung Inflammation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clinically Stable n=3 Participants Patients with cystic fibrosis and are clinically stable, 10 subjects with one copy of F508del and 4 subjects with at least one copy of G551D	Exacerbation n=11 Participants Patients with cystic fibrosis admitted for treatment of a pulmonary exacerbation with IV antibiotics, 10 subjects with one copy of F508del	Total n=14 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	11 participants n=7 Participants	14 participants n=5 Participants

PRIMARY outcome

Timeframe: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbation

Population: Regarding "Clinically Stable" Arm: Because very few neutrophils at the end of treatment for a pulmonary exacerbation were positive for IL-17, it was determined not to undertake studies examining sputum neutrophils during periods of clinical stability.

In the Exacerbation/IV Antibiotics Cohort--Subjects will serve as their own controls. The percentage of neutrophils (in sputum) positive for IL-17 was determined by flow cytometry for each subject at the beginning and end of treatment for a pulmonary exacerbation. Sputum IL-17 neutrophil counts will be compared to the change in lung function (FEV1) as determined by spirometry (American Thoracic Society standards).

Outcome measures

Outcome measures
Measure	Begining of Exacerbation n=11 Participants Study volunteer at the beginning of IV antibiotic treatment for a pulmonary exacerbation	End of Exacerbation n=11 Participants Study volunteer at the completion of 2 weeks IV antibiotic treatment for a pulmonary exacerbation
Change in Sputum IL-17 Neutrophils	55 % of neutrophils positive for IL-17 Standard Deviation 23	4 % of neutrophils positive for IL-17 Standard Deviation 9

SECONDARY outcome

Timeframe: Samples will be obtained at one outpatient clinic visit during the next calendar year

Population: Data not collected and will never be analyzed.

In the Clinically Stable Cohort--Measurement of sputum inflammatory mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and neutrophil elastase

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbation

In the Exacerbation/IV Antibiotics Cohort--Measurement of sputum inflammatory mediators by multiplex assay for IL-1β, IL-6, IL-8, and IL-17A. Neutrophil elastase determined by colorimetric assay. Measurements at the beginning of IV antibiotic treatment and after 2 weeks antibiotic treatment for a pulmonary exacerbation

Outcome measures

Outcome measures
Measure	Begining of Exacerbation n=11 Participants Study volunteer at the beginning of IV antibiotic treatment for a pulmonary exacerbation	End of Exacerbation n=11 Participants Study volunteer at the completion of 2 weeks IV antibiotic treatment for a pulmonary exacerbation
Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase IL-1b (pg/ml)	2313 pg/ml Standard Deviation 1452	757 pg/ml Standard Deviation 782
Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase IL-6 (pg/ml)	53 pg/ml Standard Deviation 26	37 pg/ml Standard Deviation 17
Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase IL-8 (pg/ml)	5785 pg/ml Standard Deviation 859	3428 pg/ml Standard Deviation 2604
Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase IL-17 (pg/ml)	302 pg/ml Standard Deviation 185	147 pg/ml Standard Deviation 152
Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase Neutrophil elastase activity (pg/ml)	195 pg/ml Standard Deviation 45	53 pg/ml Standard Deviation 45

Adverse Events

Clinically Stable

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Exacerbation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. James Chmiel

Riley Hospital for Children

Phone: 317-948-7180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place