Cystic Fibrosis
Conditions
Keywords
Lung disease, CF, Pulmozyme
Brief summary
This was a multicenter, randomized, double-blind, placebo-controlled study of patients with severe, though stable, cystic fibrosis (CF) whose routine treatment included Pulmozyme. Patients were randomized to either continue Pulmozyme or have therapy withdrawn for 2 weeks (placebo group). Patients must have had stable CF symptoms without any change in therapy for 2 weeks prior to enrollment in order to participate.
Interventions
DRUGDornase alfa
2.5 mg inhalation dose twice daily for 14±2 days
DRUGplacebo
2.5 mg inhalation dose twice daily for 14±2 days
Sponsors
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed Informed Consent Form and, if applicable, Assent Form * Age ≥ 14 years old at screening * Proven diagnosis of CF * Ability to perform acceptable and reproducible spirometry maneuvers at screening * FVC ≤ 45% predicted for race, height, age, and sex at screening * Chronic use of Pulmozyme for at least 3 months in the last year and daily or twice daily use during the 14 days prior to screening * Stable regimen of chest physiotherapy (CPT) for at least 14 days prior to screening * Ability to complete the 6-minute walk test at screening * Ability to complete the 6-minute walk test and spirometry at Visit 2 * If on routine tobramycin solution for inhalation (i.e., TOBI®) or other cycled antibiotic therapy, intention to either start or stop therapy at the time of Visit 2 (based on routine therapy cycle; no other planned change in this antibiotic regimen for 28 days before or 28 days after Visit 2) * Clinically stable with no change in medications during the 14 days prior to screening
Exclusion criteria
* Use of an investigational drug or device within 28 days prior to screening * Previous episode of acute respiratory failure requiring assisted ventilation within 2 years prior to screening * Previous lung transplant * Any cardiac disease that would contraindicate performing the 6-minute walk test * Pregnancy or nursing * Known hypersensitivity or other contraindication to the use of Pulmozyme * Previous completion or premature discontinuation of study drug or withdrawal from this study * More than one prior screening failure for this study at any time or any prior screening failure for this study within the last 28 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Distance Walked in the 6-minute Walk Test | From baseline to Day 14 | Change in distance walked was defined as (distance walked in 6 minutes at baseline \[Day 0\]) - (distance walked in 6 minutes at Day 14) in meters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pulmonary Function as Measured by FEV1 and FVC | From baseline to Day 14 | FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) were recorded at Day 0 (baseline) and Day 14. Change in FEV1 and FVC from baseline to Day 14 was reported as a percentage of values predicted for age, height, and race. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3) | 14 |
| Dornase Alfa 2.5 mg inhalation dose twice daily for 14±2 days (Visit 2 to Visit 3) | 13 |
| Total | 27 |
Baseline characteristics
| Characteristic | Placebo | Dornase Alfa | Total |
|---|---|---|---|
| Age, Continuous | 24.6 years STANDARD_DEVIATION 7 | 29.8 years STANDARD_DEVIATION 10 | 27.1 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 14 | 4 / 13 |
| serious Total, serious adverse events | 2 / 14 | 2 / 13 |
Outcome results
Primary
Change in Distance Walked in the 6-minute Walk Test
Change in distance walked was defined as (distance walked in 6 minutes at baseline \[Day 0\]) - (distance walked in 6 minutes at Day 14) in meters.
Time frame: From baseline to Day 14
Population: Randomized patients. For placebo arm: 2 placebo patients who were randomized did not complete the study and therefore had no values to calculate change from baseline computation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Distance Walked in the 6-minute Walk Test | 25.2 Meters | Standard Deviation 79.8 |
| Dornase Alfa | Change in Distance Walked in the 6-minute Walk Test | 26.9 Meters | Standard Deviation 60 |
Secondary
Change in Pulmonary Function as Measured by FEV1 and FVC
FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) were recorded at Day 0 (baseline) and Day 14. Change in FEV1 and FVC from baseline to Day 14 was reported as a percentage of values predicted for age, height, and race.
Time frame: From baseline to Day 14
Population: Randomized patients. Patients not included in this analysis did not meet ATS reproducibility criteria. Two patients in the placebo arm whose screening visit values did not meet ATS reproducibility criteria were randomized in error and completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Pulmonary Function as Measured by FEV1 and FVC | FVC | -1.2 Percentage of predicted value | Standard Deviation 4.5 |
| Placebo | Change in Pulmonary Function as Measured by FEV1 and FVC | FEV1 | -0.5 Percentage of predicted value | Standard Deviation 4.1 |
| Dornase Alfa | Change in Pulmonary Function as Measured by FEV1 and FVC | FEV1 | 0.2 Percentage of predicted value | Standard Deviation 2.8 |
| Dornase Alfa | Change in Pulmonary Function as Measured by FEV1 and FVC | FVC | 1.0 Percentage of predicted value | Standard Deviation 4.8 |