Assessment of the Safety and Efficacy of Dupilumab in Children With Asthma (Liberty Asthma Excursion)

Study Overview
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Brief Summary
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Primary Objective: To evaluate the long-term safety and tolerability of dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study. To evaluate the efficacy of dupilumab in children of 6 to <12 years of age with uncontrolled persistent asthma in the Japan sub-study. Secondary Objectives: To evaluate the long-term efficacy of dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study. To evaluate dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study with regard to: Systemic exposure. Anti-drug antibodies (ADAs). Biomarkers. To evaluate the safety and tolerability of dupilumab in pediatric patients with asthma in the Japan sub-study To evaluate dupilumab in pediatric patients with asthma in the Japan substudy with regard to: Systemic exposure, Anti-drug antibodies (ADAs), Biomarkers

Detailed Description
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Study duration per participant is approximatively 64 weeks including a 52 weeks treatment period and 12 weeks post treatment follow-up. Japan substudy: Study duration per participant is approximately 68 weeks including 3-5 weeks screening period, 52 weeks treatment period and 12 weeks post treatment follow-up period.

Official Title
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One Year Study to Evaluate the Long-term Safety and Tolerability of Dupilumab in Pediatric Patients With Asthma Who Participated in a Previous Dupilumab Asthma Clinical Study

Conditions
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Asthma

Intervention / Treatment
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* Drug: Dupilumab (SAR231893/REGN668)
* Drug: Asthma controller therapies (incl. prednisone/prednisolone)
* Drug: Asthma reliever therapies


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Pediatric patients with asthma who completed the treatment in a dupilumab asthma trial (EFC14153). Signed written informed consent/assent. Specific for Brazil: EFC14153 patients from Brazil, who prematurely discontinued Investigational Medicinal Product (IMP) to receive Yellow Fever vaccine (a live attenuated vaccine) during Yellow Fever outbreak, are allowed to be enrolled in LTS14424 after completing the required procedures in EFC14153 (completion of remaining visits and procedures until end of treatment (EOT) V28, considered as V1 for LTS14424). Patients who are not able to complete their treatment in Study EFC14153 due to the COVID-19 pandemic will be allowed to enroll into Study LTS14424. Patients who enroll in LTS14424 after completing the EFC14153 EOS visit should have eligibility for LTS14424 reevaluated including background medication check and laboratory assessments (including complete blood count [CBC] with differential and basic chemistry) within 1 month prior to LTS14424 Visit 1. For Japan sub-study Signed written inform consent/assent Children 6 to <12 years of age, with a physician diagnosis of persistent asthma for ≥12 months prior to screening Blood eosinophil count ≥150 cells/μL or fractional exhaled nitric oxide (FeNO) ≥20 parts per billion (ppb) at screening visit (Visit 0). Exclusion criteria: Any chronic lung disease other than asthma (eg, cystic fibrosis, bronchopulmonary dysplasia) which may impair lung function. Inability to follow the procedures of the study/noncompliance (eg, due to language problems or psychological disorders). Patients receiving concomitant treatment or required a new concomitant treatment prohibited in the study. Patients or his/her parent(s)/caregiver(s)/legal guardian(s) is related to the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff thereof directly involved in the conduct of the study. Patients who experienced any hypersensitivity reactions to dupilumab in a previous dupilumab study, which, in the opinion of the Investigator, could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient. Any abnormalities or adverse events at screening (last treatment visit in the study EFC14153 will be the screening visit) that per Investigator judgment would adversely affect patient's participation in this study or would require permanent IMP discontinuation. For female patients who have commenced menstruating at any time during the study and are either: Found to have a positive urine pregnancy test, or Sexually active, not using an established acceptable contraceptive method. Planned live, attenuated vaccinations during the study. Patients with active autoimmune disease or patients using immunosuppressive therapy for autoimmune disease (eg, juvenile idiopathic arthritis, inflammatory bowel disease, systemic lupus erythematosus) at enrollment. For Japan sub-study: Any chronic lung disease other than asthma (eg, cystic fibrosis, bronchopulmonary dysplasia) which may impair lung function. Inability to follow the procedures of the study/noncompliance (eg, due to language problems or psychological disorders). Patients receiving concomitant treatment or required a new concomitant treatment prohibited in the study at the screening and enrollment visits. Patients who previously have been treated with dupilumab Diagnosed with active parasitic infection (helminthes); suspected or high risk of parasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis), despite infection resolution; or unusually frequent, recurrent, or prolonged infections, per Investigator's judgment. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dupilumab<br>Doses of dupilumab will be administered every 2 weeks or every 4 weeks added to current controller medications for 52 weeks | Drug: Dupilumab (SAR231893/REGN668)<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous (sc)<br>Drug: Asthma controller therapies (incl. prednisone/prednisolone)<br>* Pharmaceutical form: powder, or solution, or pill Route of administration: inhaled, oral or parenteral<br>Drug: Asthma reliever therapies<br>* Pharmaceutical form: powder or solution Route of administration: inhaled<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients experiencing any treatment emergent adverse event (TEAE) | The number of patients experiencing any TEAE. | From Day 1 up to Week 64 | 
| Japan sub-study: Change from baseline in pre-bronchodilator percentage (%) predicted FEV1 at Week 12 | Change from baseline in pre-bronchodilator percentage (%) predicted forced expiratory volume in 1 second (FEV1) at week 12. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of severe asthma exacerbation events during the treatment period | Annualized rate of severe asthma exacerbation events during the treatment period. | From Day 1 up to Week 52 | 
| Change from baseline in % predicted FEV1 | Change from baseline in % predicted FEV1. | Baseline to Week 64 | 
| Change from baseline in absolute FEV1 | Change from baseline in absolute FEV1. | Baseline to Week 64 | 
| Change from baseline in FVC | Change from baseline in forced vital capacity (FVC). | Baseline to Week 64 | 
| Change from baseline in FEF 25 to 75% | Change from baseline in forced expiratory flow (FEF) 25-75%. | Baseline to Week 64 | 
| Serum dupilumab concentrations | Serum dupilumab concentrations. | From Day 1 up to Week 64 | 
| Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab | Incidence of treatment-emergent ADA against dupilumab. | From Day 1 up to Week 64 | 
| Blood eosinophil counts | Blood eosinophil counts. | From Day 1 up to Week 64 | 
| Serum total IgE | Serum total IgE. | From Day 1 up to Week 64 | 
| Japan sub-study: Annualized rate of severe asthma exacerbation events during the treatment period | Annualized rate of severe asthma exacerbation events, during the treatment period. | From Day 1 up to Week 52 | 
| Japan sub-study: Change from baseline in pre-bronchodilator % predicted FEV1 at Weeks 2, 4, 8, 24, 52, and 64 | Change from baseline in pre-bronchodilator % predicted FEV1 at Weeks 2, 4, 8, 24, 52, and 64. | Baseline to Week 2, 4, 8, 24, 52 and 64 | 
| Japan sub-stud: Change from baseline in absolute FEV1 | Change from baseline in absolute FEV1. | Baseline to Week 2, 4, 8, 12, 24, 52 and 64 | 
| Japan sub-study: Change from baseline in FVC | Change from baseline in FVC. | Baseline to Week 2, 4, 8, 12, 24, 52 and 64 | 
| Japan sub-study: Change from baseline in FEF 25-75% | Change from baseline in FEF 25-75%. | Baseline to Week 2, 4, 8, 12, 24, 52 and 64 | 
| Japan sub-study: Change from baseline in ACQ-IA | Change from baseline in Asthma Control Questionnaire-Interviewer Administered (ACQ-IA). | Baseline to Week 2, 4, 8, 12, 24, 36, 52, and 64 | 
| Japan sub-study: The number of patients experiencing any TEAEs | The number of patients experiencing any TEAEs. | From Day 1 up to Week 64 | 
| Japan sub-study: Serum dupilumab concentrations | Serum dupilumab concentrations. | From Day 1 up to week 64 | 
| Japan sub-study: Incidence of treatment-emergent ADA against dupilumab | Incidence of treatment-emergent ADA against dupilumab. | From Day 1 up to Week 64 | 
| Japan sub-study: Serum total immunoglobulin E (IgE) | Serum total immunoglobulin E (IgE). | From Day 1 up to Week 64 | 
| Japan sub-study: Change from Baseline in FeNO | Change from Baseline in Fractional Exhaled Nitric Oxide (FeNO). | Baseline to Weeks 2, 4, 8, 12, 24, 52, and 64 |