Study to Evaluate the Effect of Omalizumab on Improving the Tolerability of Specific Immunotherapy in Patients With Persistent Allergic Asthma

Phase 4

Completed

Conditions: Allergic Asthma

Interventions: Drug: Placebo
Drug: Omalizumab
Drug: Immunotherapy

Registration Number: NCT00267202

Lead Sponsor: Novartis

Brief Summary: This study is designed to investigate the use of omalizumab as a pretreatment for patients with persistent allergic asthma who are candidates for allergen immunotherapy (ie, allergy shots) and will test the hypothesis that omalizumab may reduce the rate of systemic reactions to immunotherapy in patients with persistent allergic asthma.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 275

Inclusion Criteria

Patients were eligible for inclusion if they met all of the following criteria:

Informed Consent

Patients who were informed of the study procedures and medications and provided their written informed consent

Demographics

Male or female
Any race
Ages 18 - 55 years
Body weight >=20 kg and <=150 kg
Total serum IgE concentration >=30 and <=700 IU/mL at Visit 0

Disease Definitions/Medications

History of at least moderate persistent allergic asthma (consistent with Global Initiative for Asthma [GINA] guidelines of >=1 year in duration
On a stable asthma treatment regimen including inhaled corticosteroids for the preceding 4 weeks
An FEV1 while withholding short-acting beta-agonists for at least 6 hours and long-acting beta-agonists for at least 12 hours, of >=75% of the predicted value at Visit 0
Evidence of reversible airway obstruction, as defined by an increase in FEV1 of >=12% between 20 to 30 minutes after 4 puffs (or less at the discretion of the investigator) of inhaled short-acting beta-agonist administration at Visit 0 or within the preceding year
Documented sensitivity to perennial aeroallergens, as evidenced by a positive skin test (wheal >=5mm greater than saline control) to at least 1 of 3 perennial aeroallergens (house dust mite, cat, or dog) at Visit 0 or within the preceding year
Average PEFR variability <=20% (calculated as [(PM PEF - AM PEF)/(PM PEF + AM PEF)/2 x 100) during the 2-week screening period
Pre-specified level of nocturnal asthma symptoms (i.e., a mean nocturnal asthma score of >0 and <=0.5) and a mean combined clinical symptom score (nocturnal, morning, and daytime) of >0 and <=3 during the screening period
Non-smoker for at least 1 year prior to Visit 1, with a smoking history of no more than 10 pack-years (i.e., 1 pack [20 cigarettes] per day for 10 years)
Judged to be in good physical and mental health (except for his/her asthma), based on medical history, physical examination, and routine laboratory data, and appeared to be able to successfully complete this trial

Exclusion Criteria

Patients were to be excluded from participation if they met any of the following criteria:

Pulmonary

History of intubation for asthma
Asthma exacerbation requiring treatment with systemic steroids within the preceding 3 months
Asthma exacerbation requiring treatment in an emergency department or a hospital admission in the preceding 6 months
Upper respiratory tract infection or sinusitis within the preceding 4 weeks
History of an anaphylactic allergic reaction (except to stinging insects, foods, or drugs other than omalizumab)
History of treatment with immunotherapy to any allergen within past 3 years
History of aspirin or non steroidal anti-inflammatory drug (NSAID)-related asthma; patients could have been included in NSAIDs use was avoided for the duration of the study

General Medical

History of or current malignancy
Any clinically significant uncontrolled systemic disease or a history of such disease (e.g., infectious, hematologic, renal, hepatic, endocrinologic, gastrointestinal, or cardiovascular disease) within the previous 3 months
Clinically significant laboratory abnormalities at Visit 1
Platelet levels <=130 x 10 9/L at visit 1
Women of childbearing potential who were not practicing a medically approved contraception method (e.g., oral, subcutaneous, mechanical, or surgical contraception), as well as women who were pregnant or nursing
History of hypersensitivity to any ingredients, including excipients (sucrose, histidine, or polysorbate 20) of the study medication or drugs related to omalizumab (e.g., monoclonal anti-bodies or polyclonal gammaglobulin)
Severe medical condition(s) that, in the view of the investigator, prohibited participation in the study
Previous treatment with omalizumab within 1 year of screening
Considered by the investigator to be potentially unreliable or who may not have reliably attended study visits
History of drug or alcohol abuse

Procedural

Unable to perform acceptable, reproducible spirometry, or PEFR measurements
Unable or unwilling to comply with the study procedures as determined during the screening phase, including adequate completion of the diary

Medications

Patient took the following medications before Visit 0. These medications were not permitted during the trial unless otherwise specified:

Oral, intravenous, intramuscular, or intra-articular corticosteroids within 4 weeks
Beta-adrenergic antagonists (including ocular preparations) within 1 week
Antihistamines within 1 week; after skin testing was completed (Visit 0), antihistamines could be used as needed for the remainder of the study
Intravenous gammaglobulin or immunosuppressants within 4 weeks
Tricyclic antidepressants within 1 week
Investigational drugs within 4 weeks

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
Placebo	Immunotherapy	The dose of placebo was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
Omalizumab	Omalizumab	The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.
Omalizumab	Immunotherapy	The dose of omalizumab was determined according to the omalizumab US product label using a dosing table nomogram that ensures patients receive at least 0.016 mg/kg/IgE (IU/ml) per 4 weeks. The study drug was administered by subcutaneous injection every 2 or 4 weeks according to the dosing table nomogram.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Systemic Allergic Reactions (SAR) to Specific Immunotherapy (SIT)	26 Weeks	The number of participants with Systemic Allergic Reactions (SAR) to Specific Immunotherapy (SIT). A SAR was captured and recorded as an outcome, not as adverse events (AEs) or SAEs. The primary analysis time point was the end of Period 4 (maintenance immunotherapy). Participants were observed for 1 hour after each immunotherapy (IT) injection visit. Allergic reactions were graded on a 4-point scale from Grade 1 to Grade 4. Grade 1: Skin symptoms, Grade 2: Gastrointestinal symptoms, Grade 3: Respiratory symptoms and Grade 4: Cardiovascular symptoms.

Secondary Outcome Measures

Name	Time	Method
Severity of First Systemic Allergic Reaction (SAR)	26 Weeks	Systemic reactions associated with immunotherapy (IT), defined as occurring within 1 hour following injection of SIT, were graded on a four-point scale: Grade 1: Skin symptoms (generalized urticaria, itching, or erythema), Grade 2: Gastrointestinal symptoms (stomach pain, nausea, or vomiting), Grade 3: Respiratory symptoms (clinically significant nasal symptoms and/or dyspnea, wheezing, persistent cough, etc.), Grade 4: Cardiovascular symptoms (cyanosis, hypotension, collapse, arrhythmias, or angina pectoris).
Number of Participants Who Achieved Target Maintenance Specific Immunotherapy (SIT) Dose	16 Weeks	Achievement of target maintenance IT dose is defined as answering 'Yes' to the question, 'Was the target maintenance SIT dose achieved?' on Visit 13, Week 16.
Number of Participants Requiring 8 to 20 Visits to Complete Cluster Specific Immunotherapy (SIT) Dosing Regimen	Up to 26 Weeks	During period 3, a cluster dosing protocol was utilized to initiate the allergen immunotherapy (IT). Participants received escalating doses of IT according to a cluster dosing titration regimen. Visits 5 through 13 were cluster visits for this study. The number of visits needed for completion of the cluster SIT dosing regimen was defined as the number of planned visits plus the number of unplanned visits needed to reach maintenance IT dose.
Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)	Up to 26 Weeks	Epinephrine for injection, antihistamines, corticosteroids for injection, inhaled beta-agonists, and oral corticosteroids, as well as other drugs used for managing acute allergic reactions to SIT, were available during all study visits. One dose of rescue medication for SAR reactions was equivalent to 1 entry of the CRF page 'concomitant medications/significant non-drug therapies associated with immunotherapy' in response to the question 'Was this medication given in response to a SAR?'