E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Allergic bronchopulmonary aspergillosis (ABPA) |
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E.1.1.1 | Medical condition in easily understood language |
ABPA is a progressive, immunologic lung disease caused by hypersensitivity to the fungus Aspergillus fumigatus (A fumigatus). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001707 |
E.1.2 | Term | Allergic bronchopulmonary aspergillosis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the efficacy of dupilumab on the annualized rate of exacerbations in patients with ABPA. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the effects of dupilumab on lung function in patients with ABPA -To evaluate the effects of dupilumab on ABPA-related exacerbations -To evaluate the effects of dupilumab on hospitalization/emergency department (ED)/urgent care visits in patients with ABPA -To evaluate the effects of dupilumab on asthma control in patients with ABPA -To evaluate the effects of dupilumab on health-related quality of life (HRQoL) in patients with ABPA -To evaluate the effects of dupilumab on radiological changes in the lungs in patients with ABPA -To evaluate the effects of dupilumab on serum total IgE and Aspergillus-specific IgE concentrations -To evaluate the effects of dupilumab on fractional exhaled nitric oxide (FeNO) levels -To evaluate safety and tolerability of dupilumab in patients with ABPA -To evaluate dupilumab concentrations in serum and the incidence of anti-dupilumab antibodies in patients with ABPA |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sputum/Blood Immunophenotyping Substudy |
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E.3 | Principal inclusion criteria |
1. Diagnoses of both ABPA and asthma. 2. On a maintenance therapy for their asthma with controller medication which must include ICS and may include 1 or more additional controller medications including a LABA, LTRA, and/or LAMA, etc for at least 12 weeks, with a stable dose and regimen with no change in the dose or frequency of administration for at least 4 weeks prior to the screening visit, and between the screening and baseline/randomization visits 3. For patients on OCS: must be on a chronic stable dose (no change in the dose) of up to 10 mg/day or 30 mg every alternate day of OCS (prednisone/prednisolone or the equivalent) for at least 4 weeks prior to the screening visit and between the screening and the baseline/randomization visit. 4. Must have experienced >=1 severe respiratory exacerbation requiring treatment with systemic corticosteroids or hospitalization or treatment in ED/urgent care within 12 months prior to the screening visit, or must have received systemic corticosteroids during 5 of the 6 months prior to the screening visit and between the screening and baseline visits.
NOTE: Other protocol defined inclusion criteria apply |
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E.4 | Principal exclusion criteria |
1. Weight less than 30.0 kilograms 2. Current smoker or e-cigarette user, cessation of smoking or e-cigarette use within 6 months prior to randomization, or >10 pack-years smoking history 3. Post-bronchodilator FEV1 <30% predicted normal at screening 4. Respiratory exacerbation requiring systemic corticosteroids within 4 weeks prior to screening and between screening and baseline visit (for patients on daily OCS, exacerbation requiring at least doubling of the daily maintenance dose of corticosteroids) 5. Upper or lower respiratory tract infection within the 4 weeks prior to screening (visit 1) or between the screening and randomization visits 6. Significant chronic pulmonary disease other than asthma complicated with ABPA (eg, physician-diagnosed bronchiectasis due to a condition other than ABPA or with a history of a positive lower respiratory culture for P aeruginosa or other multi-drug-resistant, gram-negative bacilli; cystic fibrosis; sarcoidosis; interstitial lung disease not due to ABPA; chronic obstructive pulmonary disease [COPD] not due to ABPA; hypereosinophilic syndrome; etc) or a diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts 7. Diagnosis or suspected diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA; also called Churg-Strauss Syndrome)
NOTE: Other protocol defined exclusion criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in the study is the annualized rate of severe respiratory exacerbations defined as new onset of symptoms or clinical worsening requiring systemic corticosteroid treatment for ≥3 days; for patients who are on maintenance systemic corticosteroids, at least doubling of the dose of daily systemic corticosteroids for ≥3 days (with or without antibiotic therapy if indicated) compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change from baseline in pre-bronchodilator FEV1 compared to placebo at week 24 2. Change from baseline in pre-bronchodilator FEV1 compared to placebo at week 52 3. Annualized rate of ABPA-related exacerbations, defined as severe respiratory exacerbations (as defined above) that are associated with a doubling of serum total IgE from the prior pre-exacerbation value compared to placebo 4. Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for >24 hours in an ED/urgent care facility compared to placebo 5. Change from baseline in ACQ-5 compared to placebo 6. Change from baseline in SGRQ total score compared to placebo 7. Percentage of participants achieving a reduction in the SGRQ score of 4 points or greater compared to placebo 8. Change in mucus plugging score on chest CT compared to placebo 9. Percent change from baseline in total IgE in serum compared to placebo 10. Percent change from baseline in A fumigatus-specific IgE in serum compared to placebo 11. Percent and absolute change from baseline in FeNO compared to placebo 12. Incidence of treatment-emergent adverse events (TEAEs) 13. Immunogenicity of dupilumab, as determined by the incidence, titer, and clinical impact of treatment-emergent ADA to dupilumab 14. Concentrations of functional dupilumab in serum by treatment regimen |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 24 2. Week 52 3- 12. Up to week 52 13 - 14. Up to week 64 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
France |
Germany |
Hungary |
Japan |
Netherlands |
Poland |
Romania |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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the date the last patient completes the last study visit, withdraws from the study, or is lost to follow-up (ie, the study patient can no longer be contacted by the investigator). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 4 |