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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03560466
• Other study ID #: LTS14424
• Secondary ID: 2017-003317-25U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 21, 2018
• Est. completion date: March 31, 2025

Study information

• Verified date: October 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 365
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Dupilumab (SAR231893/REGN668)
Pharmaceutical form: solution for injection Route of administration: subcutaneous (sc)
• Asthma controller therapies (incl. prednisone/prednisolone)
Pharmaceutical form: powder, or solution, or pill Route of administration: inhaled, oral or parenteral
• Asthma reliever therapies
Pharmaceutical form: powder or solution Route of administration: inhaled

Locations

Country	Name	City	State
Argentina	Investigational Site Number :0320003	Buenos Aires
Argentina	Investigational Site Number :0320004	Buenos Aires
Argentina	Investigational Site Number :0320001	Caba	Buenos Aires
Argentina	Investigational Site Number :0320002	Caba	Buenos Aires
Argentina	Investigational Site Number :0320006	Mendoza
Australia	Investigational Site Number :0360005	North Adelaide	South Australia
Brazil	Investigational Site Number :0760001	Porto Alegre	Rio Grande Do Sul
Brazil	Investigational Site Number :0760007	Porto Alegre	Rio Grande Do Sul
Brazil	Investigational Site Number :0760002	Sao Paulo	São Paulo
Brazil	Investigational Site Number :0760004	Sao Paulo	São Paulo
Brazil	Investigational Site Number :0760006	Sorocaba	São Paulo
Canada	Investigational Site Number :1240003	Quebec
Chile	Investigational Site Number :1520005	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520009	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number :1520001	Valdivia	Los Ríos
Chile	Investigational Site Number :1520002	Viña del Mar	Valparaíso
Chile	Investigational Site Number :1520007	Viña del Mar	Valparaíso
Colombia	Investigational Site Number :1700004	Antioquia
Colombia	Investigational Site Number :1700002	Cali
Hungary	Investigational Site Number :3480006	Budapest
Hungary	Investigational Site Number :3480002	Gyula
Hungary	Investigational Site Number :3480012	Mezökövesd
Hungary	Investigational Site Number :3480001	Székesfehérvár
Hungary	Investigational Site Number :3480008	Szigetvár
Hungary	Investigational Site Number :3480003	Töröbálint
Hungary	Investigational Site Number :3480007	Zalaegerszeg
Italy	Investigational Site Number :3800003	Firenze
Italy	Investigational Site Number :3800004	Padova
Italy	Investigational Site Number :3800005	Roma
Japan	Investigational Site Number :3920001	Chuo-ku	Tokyo
Japan	Investigational Site Number :3920009	Habikino-shi
Japan	Investigational Site Number :3920006	Kamakura-shi	Kanagawa
Japan	Investigational Site Number :3920002	Nagoya-shi	Aichi
Japan	Investigational Site Number :3920004	Ritto-shi	Shiga
Japan	Investigational Site Number :3920003	Sapporo-shi	Hokkaido
Japan	Investigational Site Number :3920008	Shibukawa-shi	Gunma
Japan	Investigational Site Number :3920010	Ureshino-shi	Saga
Japan	Investigational Site Number :3920007	Yaizu-shi	Shizuoka
Japan	Investigational Site Number :3920005	Yotsukaido-shi	Chiba
Lithuania	Investigational Site Number :4400005	Siauliai
Lithuania	Investigational Site Number :4400003	Utena
Lithuania	Investigational Site Number :4400001	Vilnius
Lithuania	Investigational Site Number :4400004	Vilnius
Mexico	Investigational Site Number :4840004	Chihuahua
Mexico	Investigational Site Number :4840006	Chihuahua
Mexico	Investigational Site Number :4840003	Durango, Durango
Mexico	Investigational Site Number :4840001	Monterrey, Nuevo León
Mexico	Investigational Site Number :4840002	Veracruz
Poland	Investigational Site Number :6160001	Lodz	Lódzkie
Poland	Investigational Site Number :6160002	Poznan	Wielkopolskie
Russian Federation	Investigational Site Number :6430004	Perm
Russian Federation	Investigational Site Number :6430002	Saint Petersburg
Russian Federation	Investigational Site Number :6430001	Saint-Petersburg
Russian Federation	Investigational Site Number :6430005	St Petersburg
Russian Federation	Investigational Site Number :6430003	St. Petersburg
South Africa	Investigational Site Number :7100001	Cape Town
Spain	Investigational Site Number :7240001	Barcelona	Barcelona [Barcelona]
Turkey	Investigational Site Number :7920005	Adana
Turkey	Investigational Site Number :7920001	Ankara
Turkey	Investigational Site Number :7920003	Istanbul
Turkey	Investigational Site Number :7920004	Istanbul
Ukraine	Investigational Site Number :8040007	Chernivtsi
Ukraine	Investigational Site Number :8040004	Dnipro
Ukraine	Investigational Site Number :8040005	Kharkiv
Ukraine	Investigational Site Number :8040008	Kryvyi Rig
Ukraine	Investigational Site Number :8040001	Kyiv
Ukraine	Investigational Site Number :8040002	Zaporizhzhya
Ukraine	Investigational Site Number :8040003	Zaporizhzhya
United States	Investigational Site Number :8400004	Charlotte	North Carolina
United States	Investigational Site Number :8400008	Cincinnati	Ohio
United States	Investigational Site Number :8400024	Edmond	Oklahoma
United States	Investigational Site Number :8400002	Gilbert	Arizona
United States	Investigational Site Number :8400023	Great Neck	New York
United States	Investigational Site Number :8400022	Lincoln	Nebraska
United States	Investigational Site Number :8400013	New York	New York
United States	Investigational Site Number :8400007	Rochester	New York
United States	Investigational Site Number :8400001	Rolling Hills Estates	California
United States	Investigational Site Number :8400006	Saint Louis	Missouri
United States	Investigational Site Number :8400003	San Antonio	Texas
United States	Investigational Site Number :8400012	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  Colombia,  Hungary,  Italy,  Japan,  Lithuania,  Mexico,  Poland,  Russian Federation,  South Africa,  Spain,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Change from baseline in % predicted FEV1	Change from baseline in % predicted FEV1.	Baseline to Week 64
Secondary	Change from baseline in absolute FEV1	Change from baseline in absolute FEV1.	Baseline to Week 64
Secondary	Change from baseline in FVC	Change from baseline in forced vital capacity (FVC).	Baseline to Week 64
Secondary	Change from baseline in FEF 25 to 75%	Change from baseline in forced expiratory flow (FEF) 25-75%.	Baseline to Week 64
Secondary	Serum dupilumab concentrations	Serum dupilumab concentrations.	From Day 1 up to Week 64
Secondary	Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab	Incidence of treatment-emergent ADA against dupilumab.	From Day 1 up to Week 64
Secondary	Blood eosinophil counts	Blood eosinophil counts.	From Day 1 up to Week 64
Secondary	Serum total IgE	Serum total IgE.	From Day 1 up to Week 64
Secondary	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
Secondary	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
Secondary	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
Secondary	Japan sub-study: Change from baseline in FVC	Change from baseline in FVC.	Baseline to Week 2, 4, 8, 12, 24, 52 and 64
Secondary	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
Secondary	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
Secondary	Japan sub-study: The number of patients experiencing any TEAEs	The number of patients experiencing any TEAEs.	From Day 1 up to Week 64
Secondary	Japan sub-study: Serum dupilumab concentrations	Serum dupilumab concentrations.	From Day 1 up to week 64
Secondary	Japan sub-study: Incidence of treatment-emergent ADA against dupilumab	Incidence of treatment-emergent ADA against dupilumab.	From Day 1 up to Week 64
Secondary	Japan sub-study: Serum total immunoglobulin E (IgE)	Serum total immunoglobulin E (IgE).	From Day 1 up to Week 64
Secondary	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