Efficacy and Safety of Subcutaneous Dupilumab in Participants With Asthma/Asthmatic Wheeze Aged 2 to <6 Years (LIBERTY ASTHMA TREKIDS)

Official title

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Longterm Safety of Dupilumab in Children 2 to <6 Years of Age With Uncontrolled Asthma and/or Recurrent Severe Asthmatic Wheeze

Overview

This is a parallel, Phase 3, 2-arm study to evaluate the efficacy and long-term safety of dupilumab treatment in children 2 to \<6 years of age with uncontrolled asthma and/or recurrent severe asthmatic wheeze. The study will be conducted in 2 parts. Part A will be a 52-week, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of dupilumab in children aged 2 to \<6 years old with uncontrolled asthma and/or recurrent severe asthmatic wheeze. At the end of Part A, all eligible participants will be offered participation in Part B, an optional open-label extension phase. Study details include: Part A: The study duration of part A will be up to 68 weeks consisting of a 4-week Screening, a 52week treatment period, and a 12-week post-treatment follow-up period. For participants who will chose to participate in Part B, the study duration will be up to 120 weeks (additional 52-week treatment period). Part B: For participants who will choose to participate in Part B, the study duration will be up to 120 weeks (Part A \[4-week Screening and a 52-week treatment period\] plus additional 52-week treatment period and a 12-week post-treatment follow-up period).

Detailed description

The duration per participant is up to 120 Weeks.

Interventions

• Drug Dupilumab
  Pharmaceutical form: Injection solution Route of administration: Subcutaneous
• Drug Placebo
  Pharmaceutical form: Injection solution Route of administration: Subcutaneous

Primary outcome measures

• Part A: Annualized rate of severe asthma exacerbations during the 52-week treatment period [Time frame: Baseline through Week 52]
• Part B: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and AEs leading to permanent treatment discontinuation [Time frame: Week 52 through Week 116]

Secondary outcome measures (12)

• Part A: Annualized rate of hospitalization, ER or urgent care visit for asthma exacerbation during the 52week treatment period. [Time frame: Baseline through Week 52]
• Part A: Annualized rate of moderate asthma exacerbations during the 52-week treatment period [Time frame: Baseline through Week 52]
• Part A: Cumulative ICS dose during the 52-week treatment period [Time frame: Baseline through Week 52]
• Part A: Change from baseline in weekly average use of reliever medication during the 52-week treatment period [Time frame: Baseline to Week 52]
• Part A: Mean number of days without asthma symptoms (DWAS) using the Pediatric Asthma Caregiver Diary (PACD) during the 52-week treatment period [Time frame: Baseline through Week 52]
• Part A: Change from baseline to Week 52 in daytime symptom score using the daytime record of PACD [Time frame: Baseline to Week 52]
• Part A: Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation [Time frame: Baseline through Week 52]
• Part A: Change from baseline to Week 52 in Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Scale [Time frame: Baseline to Week 52]
• Part A: Caregiver Global Impression of Change in their child's asthma control (CGI-change in asthma control) at Week 52 [Time frame: Week 52]
• Part A: Physician Global Assessment of Change of the child's asthma control (PGA-change in asthma control) at Week 52 [Time frame: Week 52]
• Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma control (CGI-asthma control) [Time frame: Baseline to Week 52]
• Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma severity (CGI-asthma severity) [Time frame: Baseline to Week 52]

Eligibility criteria

Inclusion criteria

• Participant must be 2 to <6 years of age
• Diagnosis of asthma or recurrent severe asthmatic wheeze that is not controlled with chronic ICS for at least 3 months with stable use of at least low dose ICS for ≥1 month prior to Screening Visit 1 with evidence of uncontrolled asthma and/or recurrent severe asthmatic wheeze.
• At least one additional major criterion from the modified asthma predictive index:

• Physician diagnosed Atopic Dermatitis,
• Allergic sensitization to at least 1 aeroallergen (with a positive serum IgE defined as a value ≥0.35 kU/L).

OR 2 minor criteria:

• Wheezing unrelated to colds,
• Peripheral blood eosinophilia ≥4%,
• Allergic sensitization to milk, eggs, or peanuts (defined by serum specific IgE >0.35 kU/L.
• Parent(s)/caregiver(s)/legal guardian(s) willing and able to comply with clinic visits and study-related procedures.
• Parent(s)/caregiver(s)/legal guardian(s) able to understand the study requirements.
• Participants/parent(s)/caregiver(s)/legal guardian(s), as appropriate, must be able to understand and complete study-related questionnaires
• Body weight at screening and randomization >5 kg and <30 kg.
• Parents or caregivers or legal guardian capable of giving signed informed consent.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Severe asthma with the need for chronic oral/systemic corticosteroid use (>1 month continuous) at the time of screening enrollment.
• History of a systemic hypersensitivity reaction or anaphylaxis to biologic therapy, including any excipient.
• History of prematurity (<34 weeks gestation).
• Any other chronic lung disease that would impair lung function (eg, cystic fibrosis, bronchopulmonary dysplasia) or chronic lung disease of prematurity or need for oxygen for more than 5 days in the neonatal period.
• History of life-threatening asthma (eg, requiring intubation).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 14 centers

• Phoenix Children's Hospital- Site Number : 8400001 — Phoenix
• Allervie Clinical Research - Destin- Site Number : 8400016 — Destin
• EMDA Clinical Research- Site Number : 8400026 — Miami
• Ann & Robert H. Lurie Children's Hospital of Chicago- Site Number : 8400011 — Chicago
• Allergy and Asthma Specialist- Site Number : 8400002 — Owensboro
• Mayo Clinic in Rochester - Minnesota- Site Number : 8400008 — Rochester
• UBMD Pediatrics- Site Number : 8400013 — Buffalo
• Boston Children's Health Physicians - Hawthorne- Site Number : 8400010 — Hawthorne
• … and 6 more centers

Argentina · 8 centers

• Investigational Site Number : 0320005 — Rosario
• Investigational Site Number : 0320008 — Buenos Aires
• Investigational Site Number : 0320003 — Buenos Aires
• Investigational Site Number : 0320002 — Buenos Aires
• Investigational Site Number : 0320001 — Buenos Aires
• Investigational Site Number : 0320009 — Corrientes
• Investigational Site Number : 0320006 — Córdoba
• Investigational Site Number : 0320004 — Mendoza

Spain · 7 centers

• Investigational Site Number : 7240003 — Santiago de Compostela
• Investigational Site Number : 7240001 — Barcelona
• Investigational Site Number : 7240007 — Esplugues de Llobregat
• Investigational Site Number : 7240002 — Sabadell
• Investigational Site Number : 7240006 — Jerez de la Frontera
• Investigational Site Number : 7240005 — Madrid
• Investigational Site Number : 7240004 — Valencia

Canada · 6 centers

• Investigational Site Number : 1240002 — Edmonton
• Investigational Site Number : 1240001 — Vancouver
• Investigational Site Number : 1240008 — Burlington
• Investigational Site Number : 1240007 — Hamilton
• Investigational Site Number : 1240006 — Montreal
• Investigational Site Number : 1240005 — Sherbrooke

France · 5 centers

• Investigational Site Number : 2500005 — Créteil
• Investigational Site Number : 2500001 — Lille
• Investigational Site Number : 2500004 — Nice
• Investigational Site Number : 2500002 — Paris
• Investigational Site Number : 2500003 — Paris

Italy · 5 centers

• Buzzi Children's Hospital - Investigational Site Number : 3800003 — Milan
• Investigational Site Number : 3800005 — Padua
• Ospedale Pediatrico Bambino Gesù - Investigational Site Number : 3800002 — Rome
• AOU Luigi Vanvitelli - Investigational Site Number : 3800004 — Naples
• Fondazione IRCCS Policlinico San Matteo - Investigational Site Number : 3800001 — Pavia

Japan · 5 centers

• Investigational Site Number : 3920006 — Isehara
• Investigational Site Number : 3920004 — Tsu
• Investigational Site Number : 3920003 — Ureshino
• Investigational Site Number : 3920002 — Fukuoka
• Investigational Site Number : 3920001 — Fukuoka

Hungary · 4 centers

• Investigational Site Number : 3480005 — Budapest
• Investigational Site Number : 3480004 — Debrecen
• Investigational Site Number : 3480002 — Székesfehérvár
• Investigational Site Number : 3480001 — Szigetvár

United Kingdom · 4 centers

• Investigational Site Number : 8260003 — Birmingham
• Investigational Site Number : 8260002 — Leicester
• Investigational Site Number : 8260001 — London
• Investigational Site Number : 8260004 — Bradford

Brazil · 3 centers

• Hospital Ernesto Dornelles- Site Number : 0760004 — Porto Alegre
• Clinica de Alergia Martti Antila- Site Number : 0760002 — Sorocaba
• Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo- Site Number : — São Paulo

Germany · 3 centers

• Investigational Site Number : 2760002 — Düsseldorf
• Investigational Site Number : 2760004 — Frankfurt
• Investigational Site Number : 2760001 — Leipzig

Mexico · 3 centers

• Investigational Site Number : 4840001 — San Juan del Río
• Investigational Site Number : 4840004 — Durango
• Investigational Site Number : 4840002 — Veracruz

Poland · 3 centers

• Investigational Site Number : 6160004 — Tarnów
• Investigational Site Number : 6160001 — Lodz
• Investigational Site Number : 6160003 — Warsaw

Greece · 2 centers

• Investigational Site Number : 3000001 — Athens
• Investigational Site Number : 3000003 — Athens

Czechia · 1 center

• Investigational Site Number : 2030001 — Prague

Netherlands · 1 center

• Investigational Site Number : 5280001 — Rotterdam

Identifiers

NCT: NCT06191315 · EFC14771 · 2023-504331-41 · U1111-1246-7432

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗