Trial Outcomes & Findings for Effectiveness of Pulmozyme in Infants With Cystic Fibrosis (NCT NCT00179998)

Results Overview

Change in Total HRCT Score from initiation of intervention to 6 months Modified Maffessanti HRCT Scoring System Airways 1. Bronchial Wall Thickening:1 = mild, 2 = moderate, 3 = severe 2. Bronchiectasis:1 = mild, 2 = moderate, 3 = severe 3. Axial extent of 1 or 2: 1 = central/middle, 2 = also periphery 4. Regional extent of 1 or 2: x 1 if \< 50 %, x 2 if \> 50 % 5. Gas trapping score:0 if 1 sub-segment, 1 if \< 25 %, 2 if 25 - 50 %, 3 if 50 - 75 %, 4 if \> 75 % Multiply (# 1 + # 2 + # 3) by # 4 then add # 5 Parenchyma 1. Airspace disease: 0 = none, 1 = present 2. Ground glass opacity: 0 = none, 1 = present 3. Mucous Plugging: 0 = none, 1 = present Total Score = Airway + Parenchymal Scores for RUL, LUL, RLL, and LLL Sections. The Total Score ranges from 12 to 92, with higher scores indicating greater impairment. Maximum Score = 4 x 23 = 92

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

6 months

Results posted on

2019-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	1 - rhDNase Then Placebo once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months	2 - Placebo Then rhDNase once daily nebulized vehicle Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months
Initial Period - 6 Months STARTED	12	12
Initial Period - 6 Months COMPLETED	12	12
Initial Period - 6 Months NOT COMPLETED	0	0
Crossover Period - 6 Months STARTED	12	12
Crossover Period - 6 Months COMPLETED	12	10
Crossover Period - 6 Months NOT COMPLETED	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effectiveness of Pulmozyme in Infants With Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nebulized rhDNAse Then Placebo n=12 Participants once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months then 3 ml diluent placebo delivered by nebulization given daily for 6 months	Placebo Then Nebulized rhDNAse n=12 Participants once daily nebulized vehicle Recombinant Human DNase (Pulmozyme): Comparison of 3 ml diluent placebo delivered by nebulization given daily for 6 months then 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months	Total n=24 Participants Total of all reporting groups
Age, Continuous	23.3 weeks STANDARD_DEVIATION 11.9 • n=5 Participants	48.3 weeks STANDARD_DEVIATION 36.7 • n=7 Participants	41.8 weeks STANDARD_DEVIATION 31.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Subjects will include children with CF \< 30 months old and never treated with Pulmozyme. Patients available for recruitment will include 12 newly diagnosed children \<30 months old from Nationwide Children's Hospital and 4 from Dayton Children's.

Change in Total HRCT Score from initiation of intervention to 6 months Modified Maffessanti HRCT Scoring System Airways 1. Bronchial Wall Thickening:1 = mild, 2 = moderate, 3 = severe 2. Bronchiectasis:1 = mild, 2 = moderate, 3 = severe 3. Axial extent of 1 or 2: 1 = central/middle, 2 = also periphery 4. Regional extent of 1 or 2: x 1 if \< 50 %, x 2 if \> 50 % 5. Gas trapping score:0 if 1 sub-segment, 1 if \< 25 %, 2 if 25 - 50 %, 3 if 50 - 75 %, 4 if \> 75 % Multiply (# 1 + # 2 + # 3) by # 4 then add # 5 Parenchyma 1. Airspace disease: 0 = none, 1 = present 2. Ground glass opacity: 0 = none, 1 = present 3. Mucous Plugging: 0 = none, 1 = present Total Score = Airway + Parenchymal Scores for RUL, LUL, RLL, and LLL Sections. The Total Score ranges from 12 to 92, with higher scores indicating greater impairment. Maximum Score = 4 x 23 = 92

Outcome measures

Outcome measures
Measure	Nebulized rhDNAse n=12 Participants once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months	Nebulized Saline n=12 Participants once daily nebulized vehicle
Chest CT (High Resolution Computed Tomography (HRCT) Score)	3.7 Score points Standard Deviation 21.1	6.1 Score points Standard Deviation 9.5

PRIMARY outcome

Timeframe: 6 months

Population: Children \< 30 months of age with cystic fibrosis who were given either the study drug followed by the placebo or given placebo followed by study drug. Data is not available for the second period, as the PI has retired and is no longer associated with NCH.

Change in FEV0.5 from initiation of intervention to 6 months

Outcome measures

Outcome measures
Measure	Nebulized rhDNAse n=12 Participants once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months	Nebulized Saline n=12 Participants once daily nebulized vehicle
Infant Pulmonary Function Tests (FEV0.5)	-0.1 z score Standard Deviation 1.1	-0.2 z score Standard Deviation 1.0

SECONDARY outcome

Timeframe: per 6 month interval

Population: Subjects included children \< 30 months of age who were newly diagnosed with Cystic Fibrosis. Subjects were recruited from Nationwide Children's (AKA Columbus Children's) and Dayton Children's Hospitals.

Total number of days treated with IV, oral or nebulized antibiotics over 6 initial month interval

Outcome measures

Outcome measures
Measure	Nebulized rhDNAse n=12 Participants once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months	Nebulized Saline n=12 Participants once daily nebulized vehicle
Antibiotic Treatment Days	31.7 days Standard Deviation 24.5	36.3 days Standard Deviation 20.1

Adverse Events

Nebulized rhDNAse Then Placebo(Nebulized Saline)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo (Nebulized Saline) Then rhDNAse

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nebulized rhDNAse Then Placebo(Nebulized Saline) n=12 participants at risk once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months Data is unavailable for the second period. The PI has retired and is no longer associated with the institution.	Placebo (Nebulized Saline) Then rhDNAse n=12 participants at risk Once daily nebulized saline daily for 6 months, followed by Recombinant Human DNase (Pulmozyme) in 3 ml diluent daily for 6 months Data is unavailable for the second period. The PI has retired and is no longer associated with the institution.
Respiratory, thoracic and mediastinal disorders wheezing	8.3% 1/12 • Number of events 1 • 6 months for each intervention Safety population included all participants who received either the study drug or placebo	0.00% 0/12 • 6 months for each intervention Safety population included all participants who received either the study drug or placebo

Other adverse events

Other adverse events
Measure	Nebulized rhDNAse Then Placebo(Nebulized Saline) n=12 participants at risk once daily nebulized rhDNAse Recombinant Human DNase (Pulmozyme): Comparison of 2.5 mg in 3 ml diluent delivered by nebulization given daily for 6 months with 3 ml diluent placebo delivered by nebulization given daily for 6 months Data is unavailable for the second period. The PI has retired and is no longer associated with the institution.	Placebo (Nebulized Saline) Then rhDNAse n=12 participants at risk Once daily nebulized saline daily for 6 months, followed by Recombinant Human DNase (Pulmozyme) in 3 ml diluent daily for 6 months Data is unavailable for the second period. The PI has retired and is no longer associated with the institution.
Respiratory, thoracic and mediastinal disorders cough	91.7% 11/12 • Number of events 11 • 6 months for each intervention Safety population included all participants who received either the study drug or placebo	91.7% 11/12 • Number of events 11 • 6 months for each intervention Safety population included all participants who received either the study drug or placebo

Additional Information

Dr. Robert Castile

Nationwide Children's Hospital

Phone: 614-355-6670

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place