Clinical trial NCT03560466: Assessment of the Safety and Efficacy of Dupilumab in Children With Asthma (Liberty Asthma Excursion)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2018-06-18
Enrollment: 365
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The number of patients experiencing any treatment emergent adverse event (TEAE)
timeFrame: From Day 1 up to Week 64
measure: Japan sub-study: Change from baseline in pre-bronchodilator percentage (%) predicted FEV1 at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Annualized rate of severe asthma exacerbation events during the treatment period
timeFrame: From Day 1 up to Week 52
measure: Change from baseline in % predicted FEV1
timeFrame: Baseline to Week 64
measure: Change from baseline in absolute FEV1
timeFrame: Baseline to Week 64
measure: Change from baseline in FVC
timeFrame: Baseline to Week 64
measure: Change from baseline in FEF 25 to 75%
timeFrame: Baseline to Week 64
measure: Serum dupilumab concentrations
timeFrame: From Day 1 up to Week 64
measure: Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab
timeFrame: From Day 1 up to Week 64
measure: Blood eosinophil counts
timeFrame: From Day 1 up to Week 64
measure: Serum total IgE
timeFrame: From Day 1 up to Week 64
measure: Japan sub-study: Annualized rate of severe asthma exacerbation events during the treatment period
timeFrame: From Day 1 up to Week 52
measure: Japan sub-study: Change from baseline in pre-bronchodilator % predicted FEV1 at Weeks 2, 4, 8, 24, 52, and 64
timeFrame: Baseline to Week 2, 4, 8, 24, 52 and 64
measure: Japan sub-stud: Change from baseline in absolute FEV1
timeFrame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64
measure: Japan sub-study: Change from baseline in FVC
timeFrame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64
measure: Japan sub-study: Change from baseline in FEF 25-75%
timeFrame: Baseline to Week 2, 4, 8, 12, 24, 52 and 64
measure: Japan sub-study: Change from baseline in ACQ-IA
timeFrame: Baseline to Week 2, 4, 8, 12, 24, 36, 52, and 64
measure: Japan sub-study: The number of patients experiencing any TEAEs
timeFrame: From Day 1 up to Week 64
measure: Japan sub-study: Serum dupilumab concentrations
timeFrame: From Day 1 up to week 64
measure: Japan sub-study: Incidence of treatment-emergent ADA against dupilumab
timeFrame: From Day 1 up to Week 64
measure: Japan sub-study: Serum total immunoglobulin E (IgE)
timeFrame: From Day 1 up to Week 64
measure: Japan sub-study: Change from Baseline in FeNO
timeFrame: Baseline to Weeks 2, 4, 8, 12, 24, 52, and 64
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Arizona Allergy and Immunology Research- Site Number : 8400002
state: Arizona
city: Tucson
country: United States
facility: Asthma and Airway Disease Research Center Site Number : 8400012
state: Arizona
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates Site Number : 8400001
state: California
city: Saint Louis
country: United States
facility: Division of Pulmonary Medicine and Allergy Medicine- Site Number : 8400006
state: Missouri
city: Lincoln
country: United States
facility: Somnos Clinical Research Site Number : 8400022
state: Nebraska
city: Great Neck
country: United States
facility: Northwell Health- Site Number : 8400023
state: New York
city: New York
country: United States
facility: Columbia University Medical Center- Site Number : 8400013
state: New York
city: Rochester
country: United States
facility: Rochester Regional Health- Site Number : 8400007
state: New York
city: Charlotte
country: United States
facility: Immunocarolina LLC Site Number : 8400004
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center Site Number : 8400008
state: Ohio
city: Edmond
country: United States
facility: OK Clinical Research, LLC- Site Number : 8400024
state: Oklahoma
city: San Antonio
country: United States
facility: Allergy & Asthma Research Center- Site Number : 8400003
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number : 0320002
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320001
state: Buenos Aires
city: Vicente Lopez
country: Argentina
facility: Investigational Site Number : 0320004
state: Ciudad De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Mendoza
country: Argentina
facility: Investigational Site Number : 0320006
city: North Adelaide
country: Australia
facility: Investigational Site Number : 0360005
state: South Australia
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre- Site Number : 0760001
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS- Site Number : 0760007
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Unidade Ambulatorial de Pesquisa Clinica I - NGP - UNIFESP- Site Number : 0760002
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto da Criança of Hospital das Clínicas de São Paulo- Site Number : 0760004
state: São Paulo
city: Sorocaba
country: Brazil
facility: Clinica de Alergia Martti Antila Site Number : 0760006
state: São Paulo
city: Quebec
country: Canada
facility: Investigational Site Number : 1240003
city: Valdivia
country: Chile
facility: Investigational Site Number : 1520001
state: Los Ríos
city: Santiago
country: Chile
facility: Investigational Site Number : 1520005
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520009
state: Reg Metropolitana De Santiago
city: Viña del Mar
country: Chile
facility: Investigational Site Number : 1520007
state: Valparaíso
city: Viña del Mar
country: Chile
facility: Investigational Site Number : 1520002
state: Valparaíso
city: Antioquia
country: Colombia
facility: Investigational Site Number : 1700004
city: Cali
country: Colombia
facility: Investigational Site Number : 1700002
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480006
city: Gyula
country: Hungary
facility: Investigational Site Number : 3480002
city: Mezökövesd
country: Hungary
facility: Investigational Site Number : 3480012
city: Szigetvár
country: Hungary
facility: Investigational Site Number : 3480008
city: Székesfehérvár
country: Hungary
facility: Investigational Site Number : 3480001
city: Töröbálint
country: Hungary
facility: Investigational Site Number : 3480003
city: Zalaegerszeg
country: Hungary
facility: Investigational Site Number : 3480007
city: Firenze
country: Italy
facility: Investigational Site Number : 3800003
city: Padova
country: Italy
facility: Investigational Site Number : 3800004
city: Roma
country: Italy
facility: Investigational Site Number : 3800005
city: Chiba-shi
country: Japan
facility: Investigational Site Number : 3920013
state: Chiba
city: Chuo-ku
country: Japan
facility: Investigational Site Number : 3920016
state: Chiba
city: Yotsukaido-shi
country: Japan
facility: Investigational Site Number : 3920005
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Investigational Site Number : 3920015
state: Fukuoka
city: Fukuoka-shi
country: Japan
facility: Investigational Site Number : 3920011
state: Fukuoka
city: Shibukawa
country: Japan
facility: Investigational Site Number : 3920008
state: Gunma
city: Onomichi-shi
country: Japan
facility: Investigational Site Number : 3920014
state: Hiroshima
city: Sapporo-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Hokkaido
city: Tsu-shi
country: Japan
facility: Investigational Site Number : 3920012
state: Mie
city: Ureshino-shi
country: Japan
facility: Investigational Site Number : 3920010
state: Saga
city: Habikino-Shi
country: Japan
facility: Investigational Site Number : 3920009
city: Siauliai
country: Lithuania
facility: Investigational Site Number : 4400005
city: Utena
country: Lithuania
facility: Investigational Site Number : 4400003
city: Vilnius
country: Lithuania
facility: Investigational Site Number : 4400001
city: Vilnius
country: Lithuania
facility: Investigational Site Number : 4400004
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840006
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840004
city: Durango, Durango
country: Mexico
facility: Investigational Site Number : 4840003
city: Monterrey, Nuevo León
country: Mexico
facility: Investigational Site Number : 4840001
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840002
city: Lodz
country: Poland
facility: Investigational Site Number : 6160001
state: Lódzkie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160002
state: Wielkopolskie
city: Perm
country: Russian Federation
facility: Investigational Site Number : 6430004
city: Saint Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430001
city: St Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430005
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430003
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100001
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Adana
country: Turkey
facility: Investigational Site Number : 7920005
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920001
city: İstanbul
country: Turkey
facility: Investigational Site Number : 7920003
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920004
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number : 8040007
city: Dnipro
country: Ukraine
facility: Investigational Site Number : 8040004
city: Kharkiv
country: Ukraine
facility: Investigational Site Number : 8040005
city: Kryvyi Rig
country: Ukraine
facility: Investigational Site Number : 8040008
city: Kyiv
country: Ukraine
facility: Investigational Site Number : 8040001
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site Number : 8040002
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site Number : 8040003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: