Phase 3
N=408
Evaluation of Dupilumab in Children With Uncontrolled Asthma
Asthma
Bottom Line
View on ClinicalTrials.gov: NCT02948959 ↗Enrolled (actual)
408
Serious AEs
4.7%
Results posted
Oct 2021
Primary outcome: Primary: Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population — 0.665; 0.235 exacerbations per participant-years — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Dupilumab (Drug); Placebo (Drug); Asthma Controller Therapies (Drug); Asthma Reliever Therapies (Drug)
- Age
- Pediatric · 6+ yrs
- Sex
- All
- Sponsor
- Sanofi
- Primary completion
- Aug 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
0.665; 0.235 | <0.0001 sig |
| PRIMARY Annualized Rate of Severe Exacerbation Events During the 52-Week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population |
0.748; 0.305 | <0.0001 sig |
| SECONDARY Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 (FEV1) Second at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
4.83; 10.15 | 0.0036 sig |
| SECONDARY Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 12: Type 2 Inflammatory Asthma Phenotype Population |
5.32; 10.53 | 0.0009 sig |
| SECONDARY Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version (ACQ-7-IA) at Week 24: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.88; -1.34 | <0.0001 sig |
| SECONDARY Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Week 24: Type 2 Inflammatory Asthma Phenotype Population |
-0.99; -1.32 | 0.0001 sig |
| SECONDARY Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.81; -21.40 | <0.0001 sig |
| SECONDARY Change From Baseline in Fractional Exhaled Nitric Oxide Level at Week 12: Type 2 Inflammatory Asthma Phenotype Population |
-1.13; -18.97 | <0.0001 sig |
| SECONDARY Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Type 2 Inflammatory Asthma Phenotype Population |
4.84; 8.11; 3.55; 9.97; 4.27; 10.27 | — |
| SECONDARY Change From Baseline in Pre-bronchodilator Percent Predicted Forced Expiratory Volume in 1 Second at Weeks 2, 4, 8, 24, 36 and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
3.94; 7.49; 2.19; 9.09; 2.48; 9.75 | — |
| SECONDARY Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population |
NA; NA | — |
| SECONDARY Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
366.0; NA | — |
| SECONDARY Time to First Loss of Asthma Control (LOAC) Event: Kaplan-Meier Estimates During 52-week Treatment Period: Type 2 Inflammatory Asthma Phenotype Population |
63.5; 140.0 | — |
| SECONDARY Time to First Loss of Asthma Control Event: Kaplan-Meier Estimates During 52-week Treatment Period: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
47.5; 135.0 | — |
| SECONDARY Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population |
0.08; 0.14; 0.06; 0.18; 0.09; 0.21 | — |
| SECONDARY Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
0.07; 0.13; 0.04; 0.17; 0.06; 0.20 | — |
| SECONDARY Percent Change From Baseline in Pre-Bronchodilator Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population |
8.07; 13.38; 6.73; 16.01; 7.68; 16.33 | — |
| SECONDARY Percent Change From Baseline in Pre-Bronchodilator Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
7.55; 12.76; 5.81; 15.20; 6.09; 16.01 | — |
| SECONDARY Change From Baseline in Morning (AM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
5.57; 6.50; 7.10; 12.81; 7.37; 18.05 | — |
| SECONDARY Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
7.62; 10.60; 6.92; 15.23; 5.52; 20.17 | — |
| SECONDARY Change From Baseline in Morning (AM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
5.85; 7.94; 5.62; 11.75; 5.54; 17.32 | — |
| SECONDARY Change From Baseline in Evening (PM) Peak Expiratory Flow at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
5.64; 10.02; 4.36; 13.09; 0.92; 17.51 | — |
| SECONDARY Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population |
0.07; 0.07; 0.07; 0.11; 0.10; 0.13 | — |
| SECONDARY Change From Baseline in Forced Vital Capacity at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
0.07; 0.06; 0.08; 0.09; 0.09; 0.13 | — |
| SECONDARY Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Type 2 Inflammatory Asthma Phenotype Population |
0.11; 0.28; 0.07; 0.34; 0.10; 0.39 | — |
| SECONDARY Change From Baseline in Forced Expiratory Flow 25-75% at Weeks 2, 4, 8, 12, 24, 36, 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
0.07; 0.29; 0.00; 0.33; 0.02; 0.40 | — |
| SECONDARY Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
0.61; 1.51; -0.02; 2.42; -0.79; 2.85 | — |
| SECONDARY Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
0.10; 0.52; -0.29; 1.44; -2.05; 1.81 | — |
| SECONDARY Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
-0.22; -0.18; -0.29; -0.34; -0.37; -0.39 | — |
| SECONDARY Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
-0.17; -0.13; -0.25; -0.29; -0.33; -0.40 | — |
| SECONDARY Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.24; -0.20; -0.32; -0.34; -0.38; -0.40 | — |
| SECONDARY Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.18; -0.15; -0.27; -0.29; -0.30; -0.41 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version (ACQ-5-IA) at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
-0.72; -0.77; -0.86; -1.09; -1.04; -1.24 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 5-question Version at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.63; -0.76; -0.75; -1.10; -0.98; -1.27 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Weeks 2, 4, 8, 12, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.50; -0.70; -0.64; -1.02; -0.83; -1.16 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire-Interviewer Administered, 7-question Version at Weeks 2, 4, 8, 12, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
-0.60; -0.72; -0.74; -1.03; -0.91; -1.14 | — |
| SECONDARY Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
-0.78; -0.65; -0.99; -1.02; -1.24; -1.28 | — |
| SECONDARY Change From Baseline in Number of Puffs of Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.75; -0.67; -1.02; -1.01; -1.15; -1.29 | — |
| SECONDARY Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
-0.13; -0.13; -0.16; -0.21; -0.21; -0.21 | — |
| SECONDARY Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
-0.15; -0.12; -0.19; -0.21; -0.22; -0.20 | — |
| SECONDARY Change From Baseline in Pediatric Asthma Quality of Life (QoL) Questionnaire With Standardized Activities-Interviewer Administered (PAQLQ[S] IA) Scores at Weeks 12, 24, 36, and 52: Type 2 Inflammatory Asthma Phenotype Population |
0.97; 1.08; 1.11; 1.30; 1.15; 1.48 | — |
| SECONDARY Change From Baseline in Pediatric Asthma Quality of Life Questionnaire With Standardized Activities-Interviewer Administered Scores at Weeks 12, 24, 36, and 52: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
0.90; 1.11; 1.06; 1.36; 1.07; 1.51 | — |
| SECONDARY Healthcare Resource Utilization (HCRU): Number of School and Work Days Missed Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population |
2.1; 1.0; 0.7; 0.2 | — |
| SECONDARY Healthcare Resource Utilization: Number of School and Work Days Missed Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
2.0; 0.9; 0.6; 0.2 | — |
| SECONDARY Healthcare Resource Utilization: Percentage of Participants Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Type 2 Inflammatory Asthma Phenotype Population |
17.5; 9.7; 7; 0.8 | — |
| SECONDARY Healthcare Resource Utilization: Percentage of Participants Who Had Missed Greater Than or Equal to 5 School/Work Days Due to LOAC: Baseline Blood Eosinophils >=300 Cells Per Microliter Population |
17.9; 8.6; 6; 0.6 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) |
107; 225; 6; 13 | — |
| SECONDARY Pharmacokinetics (PK) Assessment: Functional Dupilumab Concentration in Serum |
0.00; 0.00; 28566.81; 50269.81; 37741.97; 63476.17 | — |
| SECONDARY Percentage of Participants With Treatment Emergent Antidrug Antibodies (ADA) Response |
3.0; 4.4; 7.3; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Seroconversion |
62.5; 79.6 | — |
Summary
Primary Objective:
To evaluate the efficacy of dupilumab in children 6 to less than (<) 12 years of age with uncontrolled persistent asthma.
Secondary Objective:
To evaluate in children 6 to <12 years of age with uncontrolled persistent asthma:
* The safety and tolerability of dupilumab.
* The evaluate the effect of dupilumab in improving participant reported outcomes including health related quality of life.
* The dupilumab systemic exposure and incidence of anti-drug antibodies.
* The evaluate the association between dupilumab treatment and pediatric immune responses to vaccines: any vaccination for tetanus, diphtheria, pertussis and/or seasonal trivalent/quadrivalent influenza vaccine.
Eligibility Criteria
Inclusion criteria
Children 6 to =)12 months prior to screening, based on clinical history and examination, pulmonary function parameters according to Global initiative for asthma (GINA) 2015 Guidelines and the following criteria:
- Existing background therapy of medium-dose ICS with second controller medication (i.e., long-acting β2 agonist , leukotriene receptor antagonist, long acting muscarinic antagonist, or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller, for at least 3 months with a stable dose >=1 month prior to Screening Visit 1.
- Pre-bronchodilator forced expiratory volume in 1 second (FEV1) =1.5 on at least one day of the Screening Period.
- Use of reliever medication (i.e., albuterol/salbutamol or levalbuterol/levosalbutamol), other than as a preventive for exercise induced bronchospasm, on 3 or more days per week, in at least one week during the Screening Period.
- Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening Period.
- Asthma symptoms 3 or more days per week in at least one week during the Screening Period.
Exclusion criteria
- Participants =12 years of age.
- Participants with <16 kg bodyweight.
- Any other chronic lung disease (cystic fibrosis, bronchopulmonary dysplasia, etc.), which may impair lung function.
- A participant with any history of life threatening asthma (ie, extreme exacerbation that requires intubation).
- Co-morbid disease that might interfere with the evaluation of investigational medicinal product.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT02948959). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.