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

Phase 3RecruitingNCT06191315

Sanofi90 enrolled

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).

The duration per participant is up to 120 Weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Wheezing Asthma

Eligibility

Sex: ALLMin age: 2 YearsMax age: 5 Years

Medical Language ↔ Plain English

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: 1. Physician diagnosed Atopic Dermatitis, 2. Allergic sensitization to at least 1 aeroallergen (with a positive serum IgE defined as a value ≥0.35 kU/L). OR 2 minor criteria: 3. Wheezing unrelated to colds, 4. Peripheral blood eosinophilia ≥4%, 5. 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.

Outcomes

Primary Outcomes

Part A: Annualized rate of severe asthma exacerbations during the 52-week treatment period

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

Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation.

Time frame: Week 52 through Week 116

Secondary Outcomes

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

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

A day without asthma symptoms (DWAS) is defined as a day without any asthma symptoms, β-agonist use, oral steroid use, or need for urgent asthma care. The PACD consists of a daytime and overnight record. The daytime asthma symptom questions are scored on a 6-point scale from 0 (no symptoms/interference) to 5 (very severe symptoms/interference). The overnight questions are scored on a 5-point scale from 0 (no overnight cough and caregiver not disturbed at all) to 4 (coughed all night and disturbed all night).

Time frame: Baseline through Week 52

Part A: Change from baseline to Week 52 in daytime symptom score using the daytime record of PACD

The PACD consists of a daytime and overnight record. The daytime asthma symptom questions are scored on a 6-point scale from 0 (no symptoms/interference) to 5 (very severe symptoms/interference).

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

PedsQL measures health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. Scores range 0-100 with higher scores indicate better HRQOL.

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

CGI-change in asthma control is a 1-item questionnaire that asks the caregiver to provide the overall assessment of change of their child's asthma control on a 7-point scale, compared to just before he/she started taking the study treatment. Response choices are: 0 = "Very much better", 1 ="Moderately better", 2 = "A little better", 3 = "No change", 4 = "A little worse", 5 = "Moderately worse", 6 = "Very much worse".

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

The Physician Global Assessment of Change of Asthma (PGA-change in asthma control) is a 1 item questionnaire that asks the physician to provide the overall assessment of change in the child's asthma control on a 7-point scale, compared to just before he/she started taking the study treatment. Response choices are: 0 = "Very much better", 1 = "Moderately better", 2 ="A little better", 3 = "No change", 4 = "A little worse", 5 = "Moderately worse", 6 = "Very much worse".

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)

The Caregiver Global Impression of asthma control (CGI-Asthma Control) is a 1-item questionnaire that asks caregiver to provide the assessment of their child's asthma control over the past 7 days, on a 4-point scale for the past week. Response choices are: 1 = "Not controlled", 2 = "Somewhat controlled", 3 = "Moderately controlled", 4 = "Well controlled".

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)

The Caregiver Global Impression of asthma severity (CGI-Asthma Severity) is a 1-item questionnaire that asks caregivers to provide the assessment of their child's asthma control over the past 7 days, on a 4-point scale for the past week. Response choices are: 1 = "None", 2 = "Mild", 3 = "Moderate", 4 = "Severe".

Time frame: Baseline to Week 52

Part A: Change from baseline to Week 52 in Physician Global Assessment of the child's asthma control (PGA-asthma control).

The Physician Global Assessment of asthma control is a 1-item questionnaire that asks physicians to assess the control of the child's asthma in the past 7 days on a 4 point scale for the past week. Response choices are: 1 = "Not controlled", 2 = "Somewhat controlled", 3 = "Moderately controlled", 4 = "Well controlled".

Time frame: Baseline to Week 52

Part A: Change from baseline to Week 52 in Test for Respiratory and Asthma Control in Kids (TRACK)

TRACK is a validated questionnaire for caregiver completion for preschool aged children with symptoms consistent with asthma. The total score range of 0 to 100. Higher scores indicated better asthma control.

Time frame: Baseline to Week 52

Part A: Change from baseline in blood eosinophil level at Weeks 24 and 52

Time frame: Baseline to Week 24 and 52

Part A: Concentration of dupilumab in serum over time during the 52-week treatment period

Time frame: Baseline through Week 52

Part A: Incidence of treatment-emergent anti-drug antibody (ADA) against dupilumab over time

Time frame: Baseline through Week 52

Part A: IgG response to any vaccination for tetanus, diphtheria and pertussis and antibody for influenza (HAI antibody titers) vaccine administered according to vaccination schedule during the 52-week treatment period

Time frame: Baseline through Week 52

Part B: Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period

Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period.

Time frame: Week 52 through Week 104

Part B Concentration of dupilumab in serum over time during the 52-week Part B treatment period

Time frame: Week 52 through Week 104

Part B: Incidence of treatment-emergent anti-drug antibodies (ADAs) against dupilumab over time

Time frame: Week 52 through Week 104

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

Overview

Conditions

Interventions

Eligibility

Locations (75)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts