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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: Dupilumab (SAR231893/REGN668); Drug: Asthma controller therapies (incl. prednisone/prednisolone); Drug: Asthma reliever therapies

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.

• Study Type: Interventional
• Enrollment (Actual): 365
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Investigational Site Number :0320003
  • Buenos Aires, Argentina, B1602DQD
    • Investigational Site Number :0320004
  • Mendoza, Argentina, 5500
    • Investigational Site Number :0320006
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1122AAK
      • Investigational Site Number :0320002
    • Caba, Buenos Aires, Argentina, C1414AIF
      • Investigational Site Number :0320001
• Australia
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Investigational Site Number :0360005
• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
      • Investigational Site Number :0760001
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90619-900
      • Investigational Site Number :0760007
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 04037-002
      • Investigational Site Number :0760002
    • Sao Paulo, São Paulo, Brazil, 05403-000
      • Investigational Site Number :0760004
    • Sorocaba, São Paulo, Brazil, 18040-425
      • Investigational Site Number :0760006
• Canada
  • Quebec, Canada, G1V 4W2
    • Investigational Site Number :1240003
• Chile
  • Los Ríos
    • Valdivia, Los Ríos, Chile, 5090145
      • Investigational Site Number :1520001
  • Reg Metropolitana De Santiago
    • Santiago, Reg Metropolitana De Santiago, Chile, 838-0418
      • Investigational Site Number :1520005
    • Santiago, Reg Metropolitana De Santiago, Chile, 8380453
      • Investigational Site Number :1520009
  • Valparaíso
    • Viña del Mar, Valparaíso, Chile, 2520024
      • Investigational Site Number :1520007
    • Viña del Mar, Valparaíso, Chile, 2520594
      • Investigational Site Number :1520002
• Colombia
  • Antioquia, Colombia, 050010
    • Investigational Site Number :1700004
  • Cali, Colombia, 760043
    • Investigational Site Number :1700002
• Hungary
  • Budapest, Hungary, 1089
    • Investigational Site Number :3480006
  • Gyula, Hungary, 5700
    • Investigational Site Number :3480002
  • Mezökövesd, Hungary, 3400
    • Investigational Site Number :3480012
  • Szigetvár, Hungary, 7900
    • Investigational Site Number :3480008
  • Székesfehérvár, Hungary, 8000
    • Investigational Site Number :3480001
  • Töröbálint, Hungary, 2045
    • Investigational Site Number :3480003
  • Zalaegerszeg, Hungary, 8900
    • Investigational Site Number :3480007
• Italy
  • Firenze, Italy, 50139
    • Investigational Site Number :3800003
  • Padova, Italy, 35128
    • Investigational Site Number :3800004
  • Roma, Italy, 00146
    • Investigational Site Number :3800005
• Japan
  • Habikino-shi, Japan, 583-8588
    • Investigational Site Number :3920009
  • Aichi
    • Nagoya-shi, Aichi, Japan, 457-8511
      • Investigational Site Number :3920002
  • Chiba
    • Yotsukaido-shi, Chiba, Japan, 284-0003
      • Investigational Site Number :3920005
  • Gunma
    • Shibukawa-shi, Gunma, Japan, 377-8577
      • Investigational Site Number :3920008
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan, 064-0821
      • Investigational Site Number :3920003
  • Kanagawa
    • Kamakura-shi, Kanagawa, Japan, 247-0072
      • Investigational Site Number :3920006
  • Saga
    • Ureshino-shi, Saga, Japan, 843-0393
      • Investigational Site Number :3920010
  • Shiga
    • Ritto-shi, Shiga, Japan, 520-3046
      • Investigational Site Number :3920004
  • Shizuoka
    • Yaizu-shi, Shizuoka, Japan, 425-0055
      • Investigational Site Number :3920007
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0031
      • Investigational Site Number :3920001
• Lithuania
  • Siauliai, Lithuania, LT-76231
    • Investigational Site Number :4400005
  • Utena, Lithuania, LT-28151
    • Investigational Site Number :4400003
  • Vilnius, Lithuania, LT-08406
    • Investigational Site Number :4400001
  • Vilnius, Lithuania, LT-09108
    • Investigational Site Number :4400004
• Mexico
  • Chihuahua, Mexico, 31000
    • Investigational Site Number :4840006
  • Chihuahua, Mexico, 31200
    • Investigational Site Number :4840004
  • Durango, Durango, Mexico, 34080
    • Investigational Site Number :4840003
  • Monterrey, Nuevo León, Mexico, 64460
    • Investigational Site Number :4840001
  • Veracruz, Mexico, 91910
    • Investigational Site Number :4840002
• Poland
  • Lódzkie
    • Lodz, Lódzkie, Poland, 90-329
      • Investigational Site Number :6160001
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-693
      • Investigational Site Number :6160002
• Russian Federation
  • Perm, Russian Federation, 614066
    • Investigational Site Number :6430004
  • Saint Petersburg, Russian Federation, 193312
    • Investigational Site Number :6430002
  • Saint-Petersburg, Russian Federation, 194100
    • Investigational Site Number :6430001
  • St Petersburg, Russian Federation, 197101
    • Investigational Site Number :6430005
  • St. Petersburg, Russian Federation, 196158
    • Investigational Site Number :6430003
• South Africa
  • Cape Town, South Africa, 7700
    • Investigational Site Number :7100001
• Spain
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number :7240001
• Turkey
  • Adana, Turkey, 01339
    • Investigational Site Number :7920005
  • Ankara, Turkey
    • Investigational Site Number :7920001
  • Istanbul, Turkey
    • Investigational Site Number :7920004
  • İstanbul, Turkey
    • Investigational Site Number :7920003
• Ukraine
  • Chernivtsi, Ukraine, 58023
    • Investigational Site Number :8040007
  • Dnipro, Ukraine, 49101
    • Investigational Site Number :8040004
  • Kharkiv, Ukraine, 61093
    • Investigational Site Number :8040005
  • Kryvyi Rig, Ukraine, 50082
    • Investigational Site Number :8040008
  • Kyiv, Ukraine, 03115
    • Investigational Site Number :8040001
  • Zaporizhzhya, Ukraine, 69063
    • Investigational Site Number :8040002
  • Zaporizhzhya, Ukraine, 69076
    • Investigational Site Number :8040003
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Investigational Site Number :8400002
    • Tucson, Arizona, United States, 85274
      • Investigational Site Number :8400012
  • California
    • Rolling Hills Estates, California, United States, 90274
      • Investigational Site Number :8400001
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1077
      • Investigational Site Number :8400006
  • Nebraska
    • Lincoln, Nebraska, United States, 68505
      • Investigational Site Number :8400022
  • New York
    • Great Neck, New York, United States, 11021
      • Investigational Site Number :8400023
    • New York, New York, United States, 10032
      • Investigational Site Number :8400013
    • Rochester, New York, United States, 14607
      • Investigational Site Number :8400007
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Investigational Site Number :8400004
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Investigational Site Number :8400008
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Investigational Site Number :8400024
  • Texas
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number :8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dupilumab; 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); Pharmaceutical form: solution for injection Route of administration: subcutaneous (sc); 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2018
• Primary Completion (Anticipated): March 31, 2025
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: March 22, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): October 5, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisolone; Prednisone
• Other Study ID Numbers: LTS14424; 2017-003317-25 (EudraCT Number); U1111-1200-1757 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No