Asthma, Wheezing
Conditions
Brief summary
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
DRUGDupilumab
Pharmaceutical form: Injection solution Route of administration: Subcutaneous
DRUGPlacebo
Pharmaceutical form: Injection solution Route of administration: Subcutaneous
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 5 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Week 52 through Week 116 | Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation. |
| Part A: Annualized rate of severe asthma exacerbations during the 52-week treatment period | Baseline through Week 52 | Annualized rate of severe asthma exacerbations during the 52-week treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Annualized rate of moderate asthma exacerbations during the 52-week treatment period | Baseline through Week 52 | Annualized rate of moderate asthma exacerbations during the 52-week treatment period. |
| Part A: Cumulative ICS dose during the 52-week treatment period | Baseline through Week 52 | — |
| Part A: Change from baseline in weekly average use of reliever medication during the 52-week treatment period | 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 | Baseline through Week 52 | 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). |
| Part A: Change from baseline to Week 52 in daytime symptom score using the daytime record of PACD | Baseline to Week 52 | 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). |
| Part A: Incidence of TEAEs, SAEs, AESIs, and AEs leading to permanent treatment discontinuation | Baseline through Week 52 | — |
| Part A: Change from baseline to Week 52 in Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Scale | Baseline to Week 52 | 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. |
| Part A: Caregiver Global Impression of Change in their child's asthma control (CGI-change in asthma control) at Week 52 | 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". |
| Part A: Physician Global Assessment of Change of the child's asthma control (PGA-change in asthma control) at Week 52 | 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". |
| Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma control (CGI-asthma control) | Baseline to Week 52 | 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". |
| Part A: Change from baseline to Week 52 in Caregiver Global Impression of their child's asthma severity (CGI-asthma severity) | Baseline to Week 52 | 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". |
| Part A: Change from baseline to Week 52 in Physician Global Assessment of the child's asthma control (PGA-asthma control). | Baseline to Week 52 | 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". |
| Part A: Change from baseline to Week 52 in Test for Respiratory and Asthma Control in Kids (TRACK) | Baseline to Week 52 | 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. |
| Part A: Change from baseline in blood eosinophil level at Weeks 24 and 52 | Baseline to Week 24 and 52 | — |
| Part A: Concentration of dupilumab in serum over time during the 52-week treatment period | Baseline through Week 52 | — |
| Part A: Incidence of treatment-emergent anti-drug antibody (ADA) against dupilumab over time | 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 | Baseline through Week 52 | — |
| Part B: Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period | Week 52 through Week 104 | Annualized rate of severe asthma exacerbations events during the 52-week Part B treatment period. |
| Part B Concentration of dupilumab in serum over time during the 52-week Part B treatment period | Week 52 through Week 104 | — |
| Part B: Incidence of treatment-emergent anti-drug antibodies (ADAs) against dupilumab over time | Week 52 through Week 104 | — |
| Part A: Annualized rate of hospitalization, ER or urgent care visit for asthma exacerbation during the 52week treatment period. | Baseline through Week 52 | — |
Countries
Argentina, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Italy, Japan, Mexico, Netherlands, Poland, Spain, United Kingdom, United States
Outcome results
None listed