Evaluation of Dupilumab in Children With Uncontrolled Asthma (VOYAGE)

Sanofi

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Drug: Asthma Controller Therapies; Drug: Placebo; Drug: Asthma Reliever Therapies; Drug: Dupilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02948959

U1111-1179-4851 (Other Identifier)

EFC14153

2016-001607-23 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

The total study duration per participant was up to 69 weeks, consisted of a screening period of 3-5 weeks, a randomized treatment period of 52 weeks and a post-treatment period of 12 weeks.

Enrollment: 408 patients

Sex: All

Ages: 6 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

Children 6 to <12 years of age, with a physician diagnosis of persistent asthma for greater than or equal 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) <=95 percentage (%) of predicted normal or pre bronchodilator FEV1/forced vital capacity ratio <0.85 at Screening and Baseline Visits.

• Reversibility of at least 10% in FEV1 after the administration of 200 to 400 micrograms (mcg; 2 to 4 puff inhalations with metered-dose inhaler [MDI]) of albuterol/salbutamol or 45 to 90 mcg (2 to 4 puffs with MDI) of levalbuterol/levosalbutamol reliever medication before randomization (up to 3 opportunities during the same visit were allowed with a maximum of 12 puffs of reliever medication if tolerated by the participant).

• Must had experienced, within 1 year prior to Screening Visit 1, any of the following events:

  • Treatment with a systemic corticosteroid (oral or parenteral), as prescribed by a healthcare professional for worsening asthma at least once or,
  • Hospitalization or emergency visit for worsening asthma.

• Evidence of uncontrolled asthma, with at least one of the following criteria during the 4 (±1) weeks Screening Period:

  • Asthma Control Questionnaire-Interviewer Administered (ACQ-IA) ACQ-5 score >=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 <6 or >=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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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408 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo (for Dupilumab), subcutaneous (SC) injection every 2 weeks (q2w) for 52 weeks in combination with stable-dose background therapy of medium-dose inhaled corticosteroids (ICS) with a second controller medication (i.e., long-acting β2 agonist \[LABA\], long acting muscarinic antagonist \[LAMA\], leukotriene receptor antagonist \[LTRA\] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).

Treatment:

Drug: Asthma Reliever Therapies

Drug: Asthma Controller Therapies

Drug: Placebo

Dupilumab

Experimental group

Description:

Dupilumab 200 milligrams (mg) (in 1.14 milliliters \[mL\] for \>30 kilograms \[kg\] bodyweight \[BW\]) or 100 mg (in 0.67 mL for less than or equal to (\<=) 30 kg BW), SC injection q2w for 52 weeks in combination with stable-dose background therapy of medium-dose ICS with a second controller medication (i.e., LABA, LAMA, LTRA\] or methylxanthines) or high-dose ICS alone or high-dose ICS with second controller medication. Albuterol/salbutamol or levalbuterol/levosalbutamol was given as reliever medication. Participants were followed up for 12 weeks after last dose (i.e. up to Week 64).

Treatment:

Drug: Asthma Reliever Therapies

Drug: Dupilumab

Drug: Asthma Controller Therapies