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 |
To evaluate the efficacy of dupilumab on the lung function in patients with ABPA. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the effects of dupilumab on exacerbations 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 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 | No |
E.3 | Principal inclusion criteria |
1. Males and females ≥12 years of age at screening 2. Diagnoses of both ABPA and asthma. 3. 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 4. For patients on OCS: must be on a chronic stable dose (no change in the dose) of OCS of up to 10 mg/day (for patients taking daily corticosteroids) or 30 mg every alternate day (for patients taking alternate day corticosteroids) 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. 5. 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 be receiving chronic stable low-dose OCS.
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 ecigarette 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 or alternate day OCS, exacerbation requiring at least double of the 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; cystic fibrosis; sarcoidosis; interstitial lung disease not due to ABPA; chronic obstructive pulmonary disease [COPD] not due to ABPA; hypereosinophilic syndrome; etc), 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
NOTE: Other protocol defined inclusion criteria apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) 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.Annualized rate of severe respiratory exacerbations, defined as new onset of symptoms or clinical worsening of respiratory symptoms requiring systemic corticosteroid treatment for ≥3 consecutive days; for patients who are on maintenance systemic corticosteroids, at least double the dose of maintenance systemic corticosteroids for ≥3 consecutive days (with or without antibiotic therapy if indicated) 2. 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 3. Annualized rate of severe respiratory exacerbations requiring either hospitalization or observation for >24 hours in an ED/urgent care facility compared to placebo 4. Change from baseline in ACQ-5 compared to placebo 5. Change from baseline in SGRQ total score compared to placebo 6. Percentage of participants achieving a reduction in the SGRQ score of 4 points or greater compared to placebo 7. Percent change from baseline in total IgE in serum compared to placebo 8. Percent change from baseline in A fumigatus-specific IgE in serum compared to placebo 9. Percent and absolute change from baseline in FeNO compared to placebo 10. Incidence of treatment-emergent adverse events (TEAEs) 11. Immunogenicity of dupilumab, as determined by the incidence, titer, and clinical impact of treatment-emergent ADA to dupilumab 12. 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 |
1-5. Over the 24 to 52 week treatment period 6. Up to 52 weeks 7-9. Over the 24 to 52 week treatment period 10. Through the end of the 52 week treatment period 11-12. Up to 64 weeks |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 |