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

NCT ID: NCT00267202

Last Updated: 2016-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 275 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2008-04-30

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.

Conditions

Allergic Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Doses of placebo were administered subcutaneously every 2 to 4 weeks according to the US product label, depending on the patient's body weight and baseline serum IgE.

Immunotherapy

Intervention Type: DRUG

Customized allergen extracts were prepared centrally for each patient based on his/her specific skin test results. Four vials containing dilutions of the patient's extract were provided. Investigators initiated dosing according to the protocol for the cluster dosing titration regimen, beginning with vial #4 (the most dilute) and progressing to vial #1, which was the most concentrated or "maintenance" solution. Each dose was administered subcutaneously into the deltoid region as a single injection. During study visits that required multiple IT injections, each injection was to be given at least 30 minutes apart. During weeks that required multiple visits for IT injections, each visit was to be separated by at least 48 hours.

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.

Group Type: EXPERIMENTAL

Omalizumab

Intervention Type: DRUG

Doses of omalizumab were administered subcutaneously every 2 to 4 weeks according to the US product label, depending on the patient's body weight and baseline serum IgE.

Immunotherapy

Intervention Type: DRUG

Customized allergen extracts were prepared centrally for each patient based on his/her specific skin test results. Four vials containing dilutions of the patient's extract were provided. Investigators initiated dosing according to the protocol for the cluster dosing titration regimen, beginning with vial #4 (the most dilute) and progressing to vial #1, which was the most concentrated or "maintenance" solution. Each dose was administered subcutaneously into the deltoid region as a single injection. During study visits that required multiple IT injections, each injection was to be given at least 30 minutes apart. During weeks that required multiple visits for IT injections, each visit was to be separated by at least 48 hours.

Interventions

Placebo

Doses of placebo were administered subcutaneously every 2 to 4 weeks according to the US product label, depending on the patient's body weight and baseline serum IgE.

Intervention Type: DRUG

Omalizumab

Doses of omalizumab were administered subcutaneously every 2 to 4 weeks according to the US product label, depending on the patient's body weight and baseline serum IgE.

Intervention Type: DRUG

Immunotherapy

Customized allergen extracts were prepared centrally for each patient based on his/her specific skin test results. Four vials containing dilutions of the patient's extract were provided. Investigators initiated dosing according to the protocol for the cluster dosing titration regimen, beginning with vial #4 (the most dilute) and progressing to vial #1, which was the most concentrated or "maintenance" solution. Each dose was administered subcutaneously into the deltoid region as a single injection. During study visits that required multiple IT injections, each injection was to be given at least 30 minutes apart. During weeks that required multiple visits for IT injections, each visit was to be separated by at least 48 hours.

Intervention Type: DRUG

Immunotherapy

Customized allergen extracts were prepared centrally for each patient based on his/her specific skin test results. Four vials containing dilutions of the patient's extract were provided. Investigators initiated dosing according to the protocol for the cluster dosing titration regimen, beginning with vial #4 (the most dilute) and progressing to vial #1, which was the most concentrated or "maintenance" solution. Each dose was administered subcutaneously into the deltoid region as a single injection. During study visits that required multiple IT injections, each injection was to be given at least 30 minutes apart. During weeks that required multiple visits for IT injections, each visit was to be separated by at least 48 hours.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Tanox

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis

Role: STUDY_CHAIR

Novartis

Locations

Novartis

East Hanover, New Jersey, United States

Countries

United States

Related Links

http://www.novartisclinicaltrials.com

Novartis patient recruitment website

Other Identifiers

CIGE025AUS23

Identifier Type: -

Identifier Source: org_study_id