Study to Evaluate the Effect of Omalizumab on Improving t... | NCT00267202

NCT00267202

Status Module

Sponsor/Collaborators Module

Name	Class
Genentech, Inc.	INDUSTRY
Tanox	INDUSTRY

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	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.	Drug: Placebo Drug: Immunotherapy
Omalizumab	Experimental	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.	Drug: Omalizumab Drug: Immunotherapy

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Placebo	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Systemic Allergic Reactions (SAR) to Specific Immunotherapy (SIT)	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.	26 Weeks

Secondary Outcomes

Measure	Description	Time Frame
Severity of First Systemic Allergic Reaction (SAR)	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).

Eligibility Module

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](streamdown:incomplete-link)

Contacts/Locations Module

Name	Affiliation	Role
Novartis	Novartis	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Novartis		East Hanover	New Jersey		United States

References Module

Label	URL
Novartis patient recruitment website	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000136 BG001139 BG002275

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00038.2± 10.02 BG00138.2± 9.89 BG00238.2± 9.93

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00099 BG00188 BG002

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0000 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Systemic Allergic Reactions (SAR) to Specific Immunotherapy (SIT)

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.

Efficacy Population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.

Posted

Number

participants

26 Weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	All Patients

Units	Counts
Participants	OG000122 OG001126 OG002248

Title

Denominators

Categories

Title	Measurements
	OG00032 OG00117 OG00249

Secondary

Severity of First Systemic Allergic Reaction (SAR)

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).

Efficacy population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.

Posted

Number

participants

26 Weeks

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Number of Participants Who Achieved Target Maintenance Specific Immunotherapy (SIT) Dose

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.

Efficacy population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.

Posted

Number

participants

16 Weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	All Patients

Secondary

Number of Participants Requiring 8 to 20 Visits to Complete Cluster Specific Immunotherapy (SIT) Dosing Regimen

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.

Efficacy population: Consisted of all randomized patients who completed the omalizumab or placebo treatment period and received at least one dose of immunotherapy.

Posted

Number

participants

Up to 26 Weeks

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Number of Participants Requiring 0 to >=5 Doses of Rescue Medications for Systemic Allergic Reactions (SARs) to Specific Immunotherapy (SIT)

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?'

Efficacy population: Consisted of all randomized participants who completed the omalizumab or placebo treatment period, received at least one dose of immunotherapy and received rescue therapy.

Posted

Number

participants

Up to 26 Weeks

ID	Title	Description
OG000	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.			4	139	88	139
EG001	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.			3	136	91	136

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Swollen tongue	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected139 at risk EG0011 affected136 at risk
Anaphylactic reaction	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected139 at risk EG0011 affected136 at risk
Food allergy	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected139 at risk EG0011 affected136 at risk
Cellulitis staphylococcal	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected139 at risk EG0010 affected136 at risk
Benign neoplasm of spinal cord	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0000 affected139 at risk EG0011 affected136 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected139 at risk EG0010 affected136 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected139 at risk EG0011 affected136 at risk
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected139 at risk EG0011 affected136 at risk
Sexual abuse	Social circumstances	MedDRA	Systematic Assessment	EG0001 affected139 at risk EG0010 affected136 at risk
Abortion induced	Surgical and medical procedures	MedDRA	Systematic Assessment	EG0001 affected139 at risk EG0010 affected136 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site erythema	General disorders	MedDRA	Systematic Assessment	EG00020 affected139 at risk EG00122 affected136 at risk
Injection site induration	General disorders	MedDRA	Systematic Assessment	EG0008 affected139 at risk EG0018 affected136 at risk
Injection site pruritus	General disorders	MedDRA	Systematic Assessment	EG00019 affected139 at risk EG00124 affected136 at risk
Injection site reaction	General disorders	MedDRA	Systematic Assessment	EG00028 affected139 at risk EG00120 affected136 at risk
Injection site swelling	General disorders	MedDRA	Systematic Assessment	EG00014 affected139 at risk EG00116 affected136 at risk
Injection site urticaria	General disorders	MedDRA	Systematic Assessment	EG0009 affected139 at risk EG0016 affected136 at risk
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG00016 affected139 at risk EG00117 affected136 at risk
Sinusitis	Infections and infestations	MedDRA	Systematic Assessment	EG0007 affected139 at risk EG00113 affected136 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG00019 affected139 at risk EG00114 affected136 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0003 affected139 at risk EG0017 affected136 at risk
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0007 affected139 at risk EG00111 affected136 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected139 at risk EG00112 affected136 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0006 affected139 at risk EG0017 affected136 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0007 affected139 at risk EG0014 affected136 at risk

Title	Organization	Phone	Extension	Email
Clinical Director	Novartis Pharmaceuticals	862-778-1768		maria.figliomeni@novartis.com

ID	Term
C562694	Epilepsy, Idiopathic Generalized

ID	Term
D000069444	Omalizumab
D007167	Immunotherapy

Ancestor Terms

ID	Term
D000888	Antibodies, Anti-Idiotypic
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D012712	Serum Globulins
D005916	Globulins
D056747	Immunomodulation
D001691	Biological Therapy
D013812	Therapeutics

Units	Counts
Participants	OG000122 OG001126 OG002248