Study to Assess the Efficacy and Safety of Omalizumab Treatment on ICS Reduction for Severe IgE-mediated Asthma

Multicentric, Open-label, Randomized, Parallel--group Study to Evaluate the Efficacy and Safety of Omalizumab in a 12- Month Period, in Patients With Severe IgE-mediated Asthma Inadequately Controlled With High Doses of Corticosteroids.

Assess efficacy and safety of omalizumab treatment during 12 months in order to reduce the use of inhaled corticosteroid (ICS) in pediatric and adult participants with severe Immunoglobulin E (IgE)-mediated asthma inadequately controlled with high doses of corticosteroids.

This was a multicentric, open label, randomized, parallel-group study with a 12-month treatment period. Participants were assigned to one of the 2 treatment groups, omalizumab plus budesonide/formoterol or budesonide/formoterol alone.

The study comprised 4 phases:

During the 4-week run-in phase adult participants received budesonide 800 mg and formoterol 24 mg. If a participant complied with all inclusion and exclusion criteria and had received the according-to-age run-in proposed doses during the last month, the participant continued to the stable-steroid phase.

During the 16-week stable-steroid phase, adult and pediatric eligible participants were randomized to one of the two treatment groups.

During the 8-week steroid-reduction phase, adult and pediatric participants reduced 25% of the budesonide baseline dose every 2 weeks, depending of the asthma control, until they reached a 100% reduction of the baseline dose. The clinical control of asthma was defined according to criteria (GINA 2012).

Inclusion Criteria

• Male and female between 6 and 55 years old. If female, participant of childbearing potential must use a safe and efficacious birth control method.

• Asthma is considered as not well-controlled if participant has 3 or more of the following conditions:

  1. Persistent day symptoms with current therapy twice at week or more, (siblings, dyspnea, cough, chest pain, thoracic oppression).
  2. One or more night-time awakenings over the last 4 weeks.
  3. Any limitation of age-appropriated habitual activities.
  4. Need of rescue medication (short acting β2 agonist) for two or more occasions per week during the last 4 weeks before screening and 2 consecutive weeks within the 4 weeks before selection.
  5. Peak expiratory flow (PEF) or VEF1 <80% predicted or personal best (if known) this is not mandatory for pediatric participants (under 18 years old).

• Despite continuous treatment with high-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) (CSO≥ 1 mg/kg/day) with or without controllers (As per GINA 2012 definition), the subject is receiving high doses of ICS (budesonide or its equivalent) and a long-acting β2-agonists(LABA) (formoterol) for the past 12 weeks at visit 0.

• At last one documented asthma exacerbation (defined as increase asthma symptoms requiring systemic corticosteroid rescue therapy) that requires visits to the emergency room or to be hospitalized in the past 12 months. It is also considered asthma exacerbation a non-planned visit that required rescue medication (β2-agonists and/or steroid nebulization every 20 minutes or β2-agonists inhaler shots every 20 minutes).

• Positive skin test or in vitro reactivity to a perennial aeroallergen, documented during the 12 months previous screening.

• IgE total concentration ranging from 30 to 1500 UI/ml.

• Body weight between 20 to 150 kg Exclusion Criteria

• Pregnant or lactating female or without safe and efficacious birth control method if of childbearing potential.

• Currently smokers or history of smoking 10 or more packs per year.

• Ex-smokers with a history of more than 10 years of smoking. As an exception, a participant with this criterion will be considered as eligible if the FEV1 reversibility of the first spirometry reaches 12%.

• Active lung disease other than asthma.

• Use of methotrexate, gold salts, troleandomycin, cyclosporine, immunosuppressants, gammaglobulin or any other type of monoclonal antibody used during the 6 months prior to the initial visit.

• Use of omalizumab during the 4 months prior to de screening visit.

• History of renal disease, cardiovascular disease, metabolic disease, hematologic disease, gastrointestinal disease, as well as immunodeficiency or cerebrovascular disease currently under treatment but not-controlled.

• History of hepatic, neurologic, oncologic or autoimmune disease.

• Participant under suspicion of having cancer.

• Participants with history of hypersensitivity to sucrose, histidine, polysorbate 20 as well as to monoclonal antibodies or gammaglobulin.

• Hypersensitivity to omalizumab or its excipients.

• Abnormal values of the blood chemistry laboratory tests, over 2 times the upper limit normal, that are considered clinically significant.

• Underage participant or any participant under vulnerable conditions who does not live with their parents or legal guardian.