Allergic Bronchopulmonary Aspergillosis, Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis, Allergic Bronchopulmonary Aspergillosis, omalizumab, oral corticosteroid use, anti-immunoglobulin E
Brief summary
This study will evaluate the safety and efficacy of omalizumab for the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in patients with Cystic Fibrosis aged 12 years and older.
Interventions
DRUGOmalizumab
Omalizumab subcutaneous injections of 600 mg daily.
DRUGPlacebo
Placebo subcutaneous injections blinded to match experimental arm dosing regimen.
DRUGItraconazole
Itraconazole twice daily with a maximum daily dose of 400 mg.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Cystic Fibrosis complicated by Allergic Bronchopulmonary Aspergillosis (ABPA) * Oral corticosteroid use for ABPA flare * Age 12 years and older (except for Italy; ≥ 18 years) * Total serum IgE levels ≥ 500 IU/mL
Exclusion criteria
* History of cancer in the last 10 years. * History of severe allergic reactions * Pregnant and lactating women * Prior use of Xolair Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline, as Measured by the Percentage of Participants Requiring Rescue With Corticosteroids, and as Measured by the Time to Deviation From the Protocol Prescribed Steroid Tapering Regimen | 6 months of blinded treatment |
Secondary
| Measure | Time frame |
|---|---|
| Change in Allergic Bronchopulmonary Aspergillosis (ABPA) Exacerbation Rates During Double-blind Treatment Period and Open-label Treatment Period | 6 months, 12 months |
| Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline, Measured at 3 and 6 Months of Treatment | 3 months, 6 months |
| Time to Steroid Free State. | 12 months |
| Change From Baseline in Average Oral Corticosteroid Use. | 6 months, 12 months |
| Percentage of Participants Responding to Omalizumab, as Defined by a Reduction in Oral Corticosteroid Dose Use of 50% or More as Compared to Baseline | 6 months, 12 months |
Countries
Belgium, Germany, Italy, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omalizumab Eligible participants received a maximum dose of 600 mg omalizumab via subcutaneous injection for 6 months in the double-blind phase of the study. The study medication was to be administered at the same time of day. Study medication was injected subcutaneously into the upper arm in the area of the deltoid or to the thigh. A maximum 600 mg dose required 4 injections. All participants who entered the study received itraconazole twice daily, while receiving oral corticosteroids, with a maximum daily dose of 400 mg.
Patients completed double-blinded phase, entered open-label treatment period of 6 months and continued the same regimen of omalizumab of double-blinded phase. | 9 |
| Placebo Eligible participants received placebo comparator via subcutaneous injection for 6 months in the double-blind phase of the study. The study medication was to be administered at the same time of day. Study medication was injected subcutaneously into the upper arm in the area of the deltoid or to the thigh. All participants who entered the study received itraconazole twice daily, while on oral corticosteroids, with a maximum daily dose of 400 mg. | 5 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Treatment | Administrative problems | 3 | 2 |
| Blinded Treatment | Adverse Event | 1 | 0 |
| Blinded Treatment | Lack of Efficacy | 1 | 0 |
| Open Label | Administrative problems | 3 | 0 |
| Open Label | Unsatisfactory therapeutic effect | 1 | 0 |
Baseline characteristics
| Characteristic | Omalizumab | Placebo | Total |
|---|---|---|---|
| Age Continuous | 21 years STANDARD_DEVIATION 4.1 | 28 years STANDARD_DEVIATION 9.5 | 23 years STANDARD_DEVIATION 7.1 |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 5 / 5 | 6 / 7 |
| serious Total, serious adverse events | 6 / 9 | 1 / 5 | 4 / 7 |
Outcome results
Primary
Change From Baseline, as Measured by the Percentage of Participants Requiring Rescue With Corticosteroids, and as Measured by the Time to Deviation From the Protocol Prescribed Steroid Tapering Regimen
Time frame: 6 months of blinded treatment
Population: No statistical analysis was performed due to insufficient study enrollment
Secondary
Change From Baseline in Average Oral Corticosteroid Use.
Time frame: 6 months, 12 months
Population: No statistical analysis was performed due to insufficient study enrollment
Secondary
Change in Allergic Bronchopulmonary Aspergillosis (ABPA) Exacerbation Rates During Double-blind Treatment Period and Open-label Treatment Period
Time frame: 6 months, 12 months
Population: No statistical analysis was performed due to insufficient study enrollment
Secondary
Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline, Measured at 3 and 6 Months of Treatment
Time frame: 3 months, 6 months
Population: No statistical analysis was performed due to insufficient study enrollment
Secondary
Percentage of Participants Responding to Omalizumab, as Defined by a Reduction in Oral Corticosteroid Dose Use of 50% or More as Compared to Baseline
Time frame: 6 months, 12 months
Population: No statistical analysis was performed due to insufficient study enrollment
Secondary
Time to Steroid Free State.
Time frame: 12 months
Population: No statistical analysis was performed due to insufficient study enrollment