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

JRCT ID: jRCT2041210042

Registered date:16/07/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Asthma
• Date of first enrollment: 02/08/2021
• Target sample size: 354
• Countries of recruitment: Argentina,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,Colombia,Japan,Hungary,Japan,Italy,Japan,Lithuania,Japan,Mexico,Japan,Poland,Japan,Russian Federation,Japan,South Africa,Japan,Spain,Japan,Turkey,Japan,Ukraine,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Drug: Dupilumab (SAR231893/REGN668)
Pharmaceutical form: solution for injection, Route of administration: subcutaneous (sc), Doses of dupilumab will be administered every 2 weeks or every 4 weeks added to current controller medications for 52 weeks

Drug: Asthma controller therapies (incl. prednisone/prednisolone)
Pharmaceutical form: powder, or solution, or pill, Route of administration: inhaled, oral or parenteral

Drug: Asthma reliever therapies
Pharmaceutical form: powder or solution, Route of administration: inhaled

Outcome(s)

Primary Outcome

1. For main-study excluded Japan:The number of patients experiencing any treatment emergent adverse event (TEAE) [ Time Frame: From Day 1 up to Week 64 ]
The number of patients experiencing any TEAE.

2. Japan sub-study: Change from baseline in pre-bronchodilator percentage (%) predicted FEV1 at Week 12 [ Time Frame: Baseline to Week 12 ]
Change from baseline in pre-bronchodilator percentage (%) predicted forced expiratory volume in 1 second (FEV1) at week 12.

Secondary Outcome

1. For main-study excluded Japan: Annualized rate of severe asthma exacerbation events during the treatment period [ Time Frame: From Day 1 up to Week 52 ]
Annualized rate of severe asthma exacerbation events during the treatment period.

2. For main-study excluded Japan: Change from baseline in % predicted FEV1 [ Time Frame: Baseline to Week 64 ]
Change from baseline in % predicted FEV1.

3. For main-study excluded Japan: Change from baseline in absolute FEV1 [ Time Frame: Baseline to Week 64 ]
Change from baseline in absolute FEV1.

4. For main-study excluded Japan: Change from baseline in FVC [ Time Frame: Baseline to Week 64 ]
Change from baseline in forced vital capacity (FVC).

5. For main-study excluded Japan: Change from baseline in FEF 25 to 75% [ Time Frame: Baseline to Week 64 ]
Change from baseline in forced expiratory flow (FEF) 25-75%.

6. For main-study excluded Japan: Serum dupilumab concentrations [ Time Frame: From Day 1 up to Week 64 ]
Serum dupilumab concentrations.

7. For main-study excluded Japan: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab [ Time Frame: From Day 1 up to Week 64 ]
Incidence of treatment-emergent ADA against dupilumab.

8. For main-study excluded Japan: IBlood eosinophil counts [ Time Frame: From Day 1 up to Week 64 ]
Blood eosinophil counts.

9. For main-study excluded Japan: Serum total IgE [ Time Frame: From Day 1 up to Week 64 ]
Serum total IgE.

10. Japan sub-study: Annualized rate of severe asthma exacerbation events during the treatment period [ Time Frame: From Day 1 up to Week 52 ]
Annualized rate of severe asthma exacerbation events, during the treatment period.

11. Japan sub-study: Change from baseline in pre-bronchodilator % predicted FEV1 at Weeks 2, 4, 8, 24, 52, and 64 [ Time Frame: Baseline to Week 2, 4, 8, 24, 52 and 64 ]
Change from baseline in pre-bronchodilator % predicted FEV1 at Weeks 2, 4, 8, 24, 52, and 64.

12. Japan sub-stud: Change from baseline in absolute FEV1 [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64 ]
Change from baseline in absolute FEV1.

13. Japan sub-study: Change from baseline in FVC [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64 ]
Change from baseline in FVC.

14. Japan sub-study: Change from baseline in FEF 25-75% [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64 ]
Change from baseline in FEF 25-75%.

15. Japan sub-study: Change from baseline in ACQ-IA [ Time Frame: Baseline to Week 2, 4, 8, 12, 24, 36, 52, and 64 ]
Change from baseline in Asthma Control Questionnaire-Interviewer Administered (ACQ-IA).

16. Japan sub-study: The number of patients experiencing any TEAEs [ Time Frame: From Day 1 up to Week 64 ]
The number of patients experiencing any TEAEs.

17. Japan sub-study: Serum dupilumab concentrations [ Time Frame: From Day 1 up to week 64 ]
Serum dupilumab concentrations.

18. Japan sub-study: Incidence of treatment-emergent ADA against dupilumab [ Time Frame: From Day 1 up to Week 64 ]
Incidence of treatment-emergent ADA against dupilumab.

19. Japan sub-study: Serum total immunoglobulin E (IgE) [ Time Frame: From Day 1 up to Week 64 ]
Serum total immunoglobulin E (IgE).

20. Japan sub-study: Change from Baseline in FeNO [ Time Frame: Baseline to Weeks 2, 4, 8, 12, 24, 52, and 64 ]
Change from Baseline in Fractional Exhaled Nitric Oxide (FeNO).

Key inclusion & exclusion criteria

• Age minimum: >= 6age old
• Age maximum: < 12age old
• Gender: Both

Include criteria

For main-study excluded Japan:
- Pediatric patients with asthma who completed the treatment in a dupilumab asthma trial (EFC14153).
- Signed written informed consent/assent.

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 End-of-study (EOS) visit should have eligibility for LTS14424 reevaluated including background medication check and laboratory assessments (including 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/microL or fractional exhaled nitric oxide (FeNO) >=20 parts per billion (ppb) at screening visit (Visit 0).

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
For main-study excluded Japan:
- 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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT03560466,2017-003317-25