Primary objective: To evaluate the efficacy of dupilumab, compared with placebo, for reducing the use of maintenance oral corticosteroids (OCS) in patients with severe steroid-dependent asthma.Secondary objectives:To evaluate the safety and…
ID
Source
Brief title
Condition
- Allergic conditions
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage change in OCS dose while maintaining asthma control
Secondary outcome
- Proportion of patients achieving a reduction of 50% or greater in their OCS
dose while maintaining asthma control.
- Absolute reduction of OCS dose while maintaining asthma control
- Proportion of patients achieving a reduction of OCS dose to <5 mg while
maintaining asthma control
- Proportion of patients achieving a reduction of OCS dose to 0 while
maintaining asthma control
- Proportion of patients achieving maximum possible OCS dose reduction while
maintaining asthma control
Background summary
Dupilumab is under development as a potential novel treatment for asthma.
Dupilumab, a fully human monoclonal antibody, is directed against the IL-4
receptor alpha subunit (IL-4R*), which is a component of IL-4 receptors Type I
and Type II, as well as the IL-13 receptor. The binding of dupilumab to IL-4R*
results in blockade of downstream signaling initiated by both IL-4 and IL-13.
Up-regulation of IL-4 and IL-13 activity has been implicated as an important
inflammatory component of asthma disease progression. Recently published
clinical data from a Phase 2 clinical trial, demonstrated that dupilumab had a
significant clinical effect in reducing asthma exacerbations, improving lung
function and asthma control in patients with moderate to severe uncontrolled
asthma in comparison with placebo.
Study objective
Primary objective: To evaluate the efficacy of dupilumab, compared with
placebo, for reducing the use of maintenance oral corticosteroids (OCS) in
patients with severe steroid-dependent asthma.
Secondary objectives:
To evaluate the safety and tolerability of dupilumab.
To evaluate the effect of dupilumab in improving patient-reported outcomes.
To evaluate dupilumab systemic exposure and the incidence of treatment-emergent
antidrug
antibodies.
Study design
Phase III, Double blinded, Placebo controlled
Intervention
Dupilumab or placebo every 2 weeks (loading dose with a double dose) added to
current controller medications.
Study burden and risks
Risks and burdens related to blood collection and possible adverse events of
study medication
Kampenringweg 45E
Gouda 2803 PE
NL
Kampenringweg 45E
Gouda 2803 PE
NL
Listed location countries
Age
Inclusion criteria
Adult patients with a physician diagnosis of asthma for *12 months, based on the Global Initiative for Asthma (GINA) 2014 guidelines and the following criteria:;* Patients with severe asthma and a well-documented requirement for regular treatment with maintenance systemic corticosteroids in the 6 months prior to Visit 1 and using a stable OCS dose for 4 weeks prior to Visit 1.
* Existing treatment with high dose inhaled corticosteroid in combination with a second controller for at least 3 months with a stable dose of ICS for *1 month prior to Visit 1. In addition, patients requiring a third controller for their asthma are considered eligible for this study.
* Forced expiratory volume in 1 second (FEV1) <80% of predicted normal.
* Evidence of asthma as documented by either: Reversibility of at least 12% and 200 mL in FEV1 after the administration of 200 to 400 mcg (2 to 4 puffs of albuterol/salbutamol) before randomization or documented in the 12 months prior to Visit 1 OR Airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction [PC20] of <8 mg/mL) documented in the 12 months prior to Visit 1.
Exclusion criteria
* Patients <18 years of age.
* Patients who weigh <30 kg.
* Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, idiopathic pulmonary fibrosis, Churg-Strauss Syndrome, etc) which may impair lung function.
* Clinical evidence or imaging (eg, chest X-ray, computed tomography, magnetic resonance imaging) within 12 months of Visit 1 with clinically significant findings of lung disease(s) other than asthma, as per local standard of care.
* A patient who experiences a severe asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic steroids at least twice their current dose for at least 3 days) within 4 weeks before Visit 1.
* A subject who requires 12 puffs or more of rescue medication on any 1 day in the week prior to Visit 1.
* A subject who has experienced an upper or lower respiratory tract infection within the 4 weeks prior to Screening.
* Current smoker or cessation of smoking within 6 months prior to Visit 1.
* Previous smoker with a smoking history >10 pack-years.
* Comorbid disease that might interfere with the evaluation of the investigational medicinal product (IMP).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-001573-40-NL |
| Other | IND105379 |
| CCMO | NL54335.091.15 |