Phase 3
N=1,902
Evaluation of Dupilumab in Patients With Persistent Asthma (Liberty Asthma Quest)
Asthma
Bottom Line
View on ClinicalTrials.gov: NCT02414854 ↗Enrolled (actual)
1,902
Serious AEs
8.5%
Results posted
Oct 2018
Primary outcome: Primary: Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: Intent-to-Treat (ITT) Population — 0.871; 0.456; 0.970; 0.524 Exacerbation per participant-year — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Dupilumab (Drug); Placebo (Drug); Inhaled corticosteroid (ICS) therapy (Drug); Albuterol/Salbutamol (Drug); Levalbuterol/Levosalbutamol (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Sanofi
- Primary completion
- Jul 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: Intent-to-Treat (ITT) Population |
0.871; 0.456; 0.970; 0.524 | <0.0001 sig |
| PRIMARY Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 12: ITT Population |
1.76; 1.78; 1.75; 1.78; 1.92; 2.07 | <0.0001 sig |
| SECONDARY Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population |
10.16; 18.74; 11.87; 20.89 | <0.0001 sig |
| SECONDARY Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.15 Giga/L |
1.007; 0.445; 1.081; 0.434 | <0.0001 sig |
| SECONDARY Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L |
1.77; 1.81; 1.75; 1.79; 0.17; 0.34 | <0.0001 sig |
| SECONDARY Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil >=0.3 Giga/L |
1.081; 0.370; 1.236; 0.403 | <0.0001 sig |
| SECONDARY Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L |
1.78; 1.81; 1.73; 1.75; 0.19; 0.39 | <0.0001 sig |
| SECONDARY Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With Baseline Eosinophil <0.3 Giga/L |
0.675; 0.512; 0.732; 0.610 | 0.2599 |
| SECONDARY Annualized Rate of Severe Exacerbation Events During The 52-Week Treatment Period: ITT Population With High Dose ICS at Baseline |
1.040; 0.560; 1.038; 0.639 | — |
| SECONDARY Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline |
0.14; 0.27; 0.20; 0.32 | — |
| SECONDARY Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities (AQLQ [S]) Self-Administered Global Score at Week 24: ITT Population |
4.26; 4.31; 4.30; 4.28; 5.23; 5.46 | — |
| SECONDARY Change From Baseline in AQLQ (S) Self- Administered Global Score at Week 24: ITT Population With Baseline Eosinophil >=0.3 Giga/L |
4.24; 4.24; 4.21; 4.36; 0.97; 1.39 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire 5-item Version (ACQ-5) Score at Week 24: ITT Population |
2.71; 2.76; 2.77; 2.77; 1.67; 1.33 | — |
| SECONDARY Annualized Rate of Severe Exacerbation Events Resulting in Hospitalization or Emergency Room Visit During The 52-Week Treatment Period: ITT Population |
0.081; 0.043; 0.034; 0.025 | — |
| SECONDARY Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil <0.3 Giga/L |
0.12; 0.21; 0.17; 0.21 | — |
| SECONDARY Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.3 Giga/L |
13.40; 26.41; 13.05; 30.58 | — |
| SECONDARY Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With High Dose ICS at Baseline |
8.47; 17.99; 13.22; 23.41 | — |
| SECONDARY Percent Change From Baseline in Pre-Bronchodilator FEV1 at Week 12: ITT Population With Baseline Eosinophil >=0.15 Giga/L |
11.43; 22.04; 13.49; 24.04 | — |
| SECONDARY Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population |
0.08; 0.22; 0.10; 0.25; 0.13; 0.24 | — |
| SECONDARY Percent Change From Baseline in Pre-Bronchodilator FEV1 at Weeks 2, 4, 8, 24, 36, and 52: ITT Population |
5.78; 14.32; 6.60; 17.38; 9.61; 16.11 | — |
| SECONDARY Change From Baseline in Percent Predicted FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
2.58; 7.10; 3.32; 8.44; 4.55; 7.92 | — |
| SECONDARY Change From Baseline in Morning (AM)/Evening (PM) Peak Expiratory Flow (PEF) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
4.19; 15.21; 3.45; 14.46; 6.23; 21.81 | — |
| SECONDARY Change From Baseline in Forced Vital Capacity (FVC) at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
0.08; 0.23; 0.10; 0.25; 0.12; 0.26 | — |
| SECONDARY Change From Baseline in Forced Expiratory Flow (FEF) 25-75% at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
0.09; 0.22; 0.11; 0.27; 0.16; 0.24 | — |
| SECONDARY Change From Baseline in Post-Bronchodilator FEV1 at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
-0.07; 0.10; -0.04; 0.09; -0.02; 0.10 | — |
| SECONDARY Annualized Rate of Loss of Asthma Control (LOAC) Event During The 52-Week Treatment Period: ITT Population |
2.972; 1.853; 2.965; 1.740 | — |
| SECONDARY Time to First Severe Exacerbation Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population |
0.165; 0.094; 0.193; 0.137; 0.275; 0.177 | — |
| SECONDARY Time to First LOAC Event: Kaplan-Meier Estimates During The 52-Week Treatment Period: ITT Population |
110.0; 230.0; 102.0; 264.0 | — |
| SECONDARY Change From Baseline in ACQ-5 Score at Weeks 2, 4, 8, 12, 36, and 52: ITT Population |
-0.52; -0.88; -0.58; -0.89; -0.76; -1.07 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire 7-item Version (ACQ-7) Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
-0.46; -0.79; -0.50; -0.82; -0.65; -0.94 | — |
| SECONDARY Change From Baseline in Morning Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
-0.07; -0.18; -0.09; -0.15; -0.16; -0.26 | — |
| SECONDARY Change From Baseline in Evening Asthma Symptom Score at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
-0.05; -0.17; -0.06; -0.16; -0.11; -0.27 | — |
| SECONDARY Change From Baseline in Number of Nocturnal Awakenings Per Night at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
-0.06; -0.15; -0.04; -0.11; -0.10; -0.19 | — |
| SECONDARY Change From Baseline in Number of Puffs of Daily Reliever Medication Used Per 24 Hours at Weeks 2, 4, 8, 12, 24, 36, and 52: ITT Population |
-0.21; -0.56; -0.10; -0.47; -0.26; -0.68 | — |
| SECONDARY Change From Baseline in AQLQ (S) Self-Administered Global Score at Weeks 12, 36, and 52: ITT Population |
0.90; 1.09; 0.94; 1.09; 1.05; 1.26 | — |
| SECONDARY Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Scores at Weeks 12, 24, 36, and 52: ITT Population |
0.07; 0.09; 0.08; 0.09; 0.07; 0.09 | — |
| SECONDARY Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Weeks 12, 24, 36, and 52: ITT Population |
-2.11; -1.91; -1.55; -1.98; -2.17; -1.93 | — |
| SECONDARY Change From Baseline in 22-Item Sino Nasal Outcome Test (SNOT-22) Score at Weeks 12, 24, 36, and 52: ITT Population With Bilateral Nasal Polyposis/Chronic Rhinosinusitis |
-6.82; -13.55; -11.30; -16.07; -7.21; -14.68 | — |
| SECONDARY Change From Baseline in Standardized Rhinoconjunctivitis Quality Of Life Questionnaire, Ages 12+ (RQLQ[S]+12) Score at Weeks 12, 24, 36, and 52: ITT Population With Comorbid Allergic Rhinitis |
-0.50; -0.70; -0.44; -0.64; -0.50; -0.73 | — |
Summary
Primary Objective:
To evaluate the efficacy of dupilumab (SAR231893 / REGN668) in participants with persistent asthma.
Secondary Objectives:
* To evaluate the safety and tolerability of dupilumab.
* To evaluate the effect of dupilumab on improving participant-reported outcomes including health-related quality of life.
* To evaluate dupilumab systemic exposure and incidence of anti-drug antibodies.
Eligibility Criteria
Inclusion criteria
-Adults and adolescent participants with a physician diagnosis of asthma for ≥12 months, based on the Global Initiative for Asthma (GINA) 2014 Guidelines and the following criteria:
a) Existing treatment with medium to high dose ICS (≥250 mcg of fluticasone propionate twice daily or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or equivalent) in combination with a second controller (eg, long-acting beta agonist, leukotriene receptor antagonist) for at least 3 months with a stable dose ≥1 month prior to Visit 1.
i) Note for Japan: for participants aged 18 years and older, ICS must be on ≥200 mcg of fluticasone propionate twice daily or equivalent; for participants aged 12 to 17 years, ICS must be ≥100 mcg of fluticasone propionate twice daily or equivalent).
ii) Participants requiring a third controller for their asthma will be considered eligible for this study, and it should also be used for at least 3 months with a stable dose ≥1 month prior to Visit 1.
Exclusion criteria
- Participants 10 pack-years.
- Comorbid disease that might interfere with the evaluation of Investigational Medicinal Product.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Data sourced from ClinicalTrials.gov (NCT02414854). 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.