Cystic Fibrosis
Conditions
Keywords
Pulmozyme, CF
Brief summary
This was a Phase IV, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the effect of Pulmozyme on pulmonary function, health-related quality of life (HRQOL), and respiratory symptoms in 3- to 5-year-old children with cystic fibrosis (CF). Approximately 40 patients were planned to be enrolled in this study. However, only 3 patients were eligible for random allocation and received treatment: 1 patient in the Pulmozyme group and 2 patients in the placebo group. All 3 patients completed the study assessments but did not have usable pulmonary function test (PFT) data.
Interventions
DRUGDornase alfa
2.5 mL (2.5 mg) dornase alfa nebulized once daily for 16 (+/-2) days
DRUGPlacebo
2.5 mL (2.5 mg) placebo nebulized once daily for 16 (+/-2) days
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form * Aged 3-5 years * Diagnosis of cystic fibrosis
Exclusion criteria
* Children taking scheduled inhaled Pulmozyme or hypertonic saline within 56 days prior to Visit 1 or any Pulmozyme in the 28 days before Visit 1 * Involvement in a clinical intervention trial within the 4 weeks prior to Visit 1 * Use of an investigational drug or device within 28 days prior to Visit 1 * Any other condition that might increase the risk of participation to the patient in the judgement of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Reactance at 8 Hz (Xrs8) From Visit 2 to Visit 3 (Change From Baseline at Visit 2 to Visit 3, After Study Drug Treatment). | from Visit 2 to Visit 3 (16 +/- 2 days) | The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Reactance is complex measure that incorporates the changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency. (8Hz was used for the primary endpoint). Reactance is thought to reflect the elastic properties of the lung. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Reactance at 4, 6, and 10 Hz (Xrs4, Xrs6, and Xrs10) | from Visit 2 to Visit 3 (16 +/- 2 days) | The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Reactance is complex measure that incorporates the changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency. (8Hz was used for the primary endpoint). Reactance is thought to reflect the elastic properties of the lung. |
| Change in Resistance at 4, 6, 8, and 10 Hz (Rrs4, Rrs6, Rrs8, and Rrs10) | from Visit 2 to Visit 3 (16 +/- 2 days) | The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Resistance is complex measure that incorporates the lack of changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency. (10Hz was used for the secondary endpoint). |
| Change in Respiratory Symptom Domain Score From the Cystic Fibrosis Questionnaire Revised (CFQ-R) for Parents of Preschoolers and for Preschoolers | from Visit 2 to Visit 3 (16 +/- 2 days) | The CFQ-R for Preschoolers and the CFQ-R for Parents of Preschoolers was designed specifically to measure the impact of CF for patients with a diagnosis of CF. Each question is answered using a 4-point Likert scale. In order to calculate the domain/symptom scale scores, the following algorithm is followed * Re-number items which have been reverse coded * Calculate the mean of the items to be included. If more than half of the items are missing, then the score is considered missing * Re-scale to result in a scaled score which ranges from 0 to 100, with higher scores indicating better health |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dornase Alfa 2.5 mL (2.5 mg) dornase alfa nebulized once daily for 16 (+/-2) days | 1 |
| Placebo 2.5 mL (2.5 mg) placebo nebulized once daily for 16 (+/-2) days | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Dornase Alfa | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 5.6 years | 4.6 years STANDARD_DEVIATION 1.5 | 4.9 years STANDARD_DEVIATION 1.2 |
| Gender Female | 1 Participants | 0 Participants | 1 Participants |
| Gender Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
Change in Reactance at 8 Hz (Xrs8) From Visit 2 to Visit 3 (Change From Baseline at Visit 2 to Visit 3, After Study Drug Treatment).
The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Reactance is complex measure that incorporates the changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency. (8Hz was used for the primary endpoint). Reactance is thought to reflect the elastic properties of the lung.
Time frame: from Visit 2 to Visit 3 (16 +/- 2 days)
Population: Children were unable to perform forced oscillometry (FOT) or did not remain stable during the study. No efficacy analyses were performed because no patients had complete (pre- or post-treatment) data for pulmonary function tests, including FOT.
Secondary
Change in Reactance at 4, 6, and 10 Hz (Xrs4, Xrs6, and Xrs10)
The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Reactance is complex measure that incorporates the changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency. (8Hz was used for the primary endpoint). Reactance is thought to reflect the elastic properties of the lung.
Time frame: from Visit 2 to Visit 3 (16 +/- 2 days)
Population: Children were unable to perform forced oscillometry (FOT) or did not remain stable during the study. No efficacy analyses were performed because no patients had complete (pre- or post-treatment) data for pulmonary function tests, including FOT.
Secondary
Change in Resistance at 4, 6, 8, and 10 Hz (Rrs4, Rrs6, Rrs8, and Rrs10)
The fundamental principle of forced oscillometry is that lung function can be assessed by measuring changes in pressure and flow in response to external pressure applied at the airway opening. Resistance is complex measure that incorporates the lack of changes in pressure and volume and the rate of these changes in response to pressure oscillations at a specific frequency. (10Hz was used for the secondary endpoint).
Time frame: from Visit 2 to Visit 3 (16 +/- 2 days)
Population: Children were unable to perform forced oscillometry (FOT) or did not remain stable during the study. No efficacy analyses were performed because no patients had complete (pre- or post-treatment) data for pulmonary function tests, including FOT.
Secondary
Change in Respiratory Symptom Domain Score From the Cystic Fibrosis Questionnaire Revised (CFQ-R) for Parents of Preschoolers and for Preschoolers
The CFQ-R for Preschoolers and the CFQ-R for Parents of Preschoolers was designed specifically to measure the impact of CF for patients with a diagnosis of CF. Each question is answered using a 4-point Likert scale. In order to calculate the domain/symptom scale scores, the following algorithm is followed * Re-number items which have been reverse coded * Calculate the mean of the items to be included. If more than half of the items are missing, then the score is considered missing * Re-scale to result in a scaled score which ranges from 0 to 100, with higher scores indicating better health
Time frame: from Visit 2 to Visit 3 (16 +/- 2 days)
Population: Children were unable to perform forced oscillometry (FOT) or did not remain stable during the study. No efficacy analyses were performed because no patients had complete (pre- or post-treatment) data for pulmonary function tests, including FOT.