A Safety Study of Xolair (Omalizumab) in Patients With Ch... | NCT01264939

NCT01264939

ID	Type	Description	Link
GA00889	Other Identifier	Hoffmann-La Roche

Status Module

Sponsor/Collaborators Module

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	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Drug: Placebo Drug: H1 antihistamine, H2 antihistamine, leukotriene receptor antagonist Drug: Diphenhydramine
Omalizumab 300 mg	Experimental	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.	Drug: Omalizumab Drug: H1 antihistamine, H2 antihistamine, leukotriene receptor antagonist Drug: Diphenhydramine

Name	Type	Description	Arm Group Labels	Other Names
Omalizumab	Drug	Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.	Omalizumab 300 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Adverse Events	The percentage of participants with serious adverse events and other adverse events is summarized by MedDRA preferred terms and organ classes in the Reported Adverse Events section below.	Baseline to the end of study (up to 40 weeks)

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 12 in the Weekly Itch Severity Score	The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosis of chronic idiopathic urticaria (CIU) refractory to H1 antihistamines, H2 blockers, and/or leukotriene receptor antagonists (LTRA) at the time of randomization.
- The presence of itch and hives for > 6 consecutive weeks at any time prior to enrollment despite current use of H1 antihistamine (up to 4 times the approved dosage), H2 blocker, and/or LTRA treatment during this time.
- Urticaria activity score over 7 days (UAS7) score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Week 0).
- In-clinic UAS ≥ 4 on at least one of the screening visit days (Day -14, Day -7, or Day 1).
For women of childbearing potential, agreement to use an acceptable form of contraception and to continue its use for the duration of the study.

Exclusion Criteria:

Treatment with an investigational agent within 30 days prior to screening.
Weight less than 20 kg (44 lbs).
Clearly defined underlying etiology for chronic urticarias other than CIU.
Evidence of parasitic infection.
Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, or other skin disease associated with itch.
Previous treatment with omalizumab within a year prior to screening.
Routine doses of the following medications within 30 days prior to screening: Systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.
Intravenous (IV) immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to screening.
Regular (daily/every other day) doxepin (oral) use within 6 weeks prior to screening.
Patients with current malignancy, history of malignancy, or currently under work-up for suspected malignancy except non-melanoma skin cancer that has been treated or excised and is considered resolved.
Hypersensitivity to omalizumab or any component of the formulation.
History of anaphylactic shock.
Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic, or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients.
Evidence of current drug or alcohol abuse.

Contacts/Locations Module

Name	Affiliation	Role
Edward R. Conner, M.D.	Genentech, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Scottsdale	Arizona	85251	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29655772	Derived	Ferrer M, Gimenez-Arnau A, Saldana D, Janssens N, Balp MM, Khalil S, Risson V. Predicting Chronic Spontaneous Urticaria Symptom Return After Omalizumab Treatment Discontinuation: Exploratory Analysis. J Allergy Clin Immunol Pract. 2018 Jul-Aug;6(4):1191-1197.e5. doi: 10.1016/j.jaip.2018.04.003. Epub 2018 Apr 12.
28390587	Derived

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	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
FG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

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

Modified intent-to-treat (mITT) population: All randomized participants who received at least 1 dose of study drug. One participant (randomized to placebo) did not receive study drug and was not included in the mITT population.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
BG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
BG002	Total	Total of all reporting groups

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
	OG000-4.01± 5.87 OG001-8.55± 6.01

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null hypothesis was that there was no difference between the placebo and the omalizumab 300 mg groups.	ANCOVA	Covariates included in the analysis were baseline weekly itch severity score (< 13 vs ≥ 13) and baseline weight (< 80 kg vs ≥ 80 kg).	<0.0001	Multiplicity plan applied to the efficacy endpoints provided strong control of the type I error rate at 0.05 level by pre-specifying the hierarchical order of the efficacy endpoint tests.	Least squares mean difference	-4.52			2-Sided	95	-5.97	-3.08				No	Superiority or Other

Secondary

Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7)

The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity. A negative change score indicates improvement.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Secondary

Change From Baseline to Week 12 in the Weekly Number of Hives Score

The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Units	Counts
Participants

Secondary

Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12

The time to the MID response is the number of weeks from the start of treatment (Baseline) until the time point at which the first MID response occurs. The MID response is defined as a reduction ≥ 5 points from Baseline in the weekly itch severity score. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug. Only patients with a MID response were included in the analysis.

Posted

Median

95% Confidence Interval

Weeks

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Secondary

Percentage of Participants With a UAS7 Score ≤ 6 at Week 12

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Posted

Number

Percentage of participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Units	Counts

Secondary

Percentage of Weekly Itch Severity Score MID Responders at Week 12

The percentage of participants with an itch severity score at 12 Weeks at least 5 points lower than at Baseline. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Posted

Number

Percentage of participants

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score

The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score indicates a reduction in hive size.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12

The DLQI is a 10-item dermatology-specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score indicates improvement.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug and who had a DLQI score at Week 12.

Posted

Mean

Standard Deviation

Units on a scale

Baseline to Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Units	Counts
Participants

Secondary

Percentage of Angioedema-free Days From Week 4 to Week 12

The percentage of angioedema-free days from Weeks 4 to 12 was defined as the number of days for which a patient responded "No" to the angioedema question in the daily diary divided by the total number of days with a non-missing diary entry, starting at the Week 4 visit and ending the day prior to the Week 12 visit.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug. Patients who withdrew before the Week 4 visit or who had missing responses for more than 40% of the daily diary entries between the Week 4 visit and the Week 12 visit were not included in the analysis.

Posted

Mean

Standard Deviation

Percentage of days

Week 4 to Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Units	Counts
Participants

Secondary

Percentage of Complete Responders (UAS7 = 0) at Week 12

A complete responder was defined as a participant with a UAS7 score = 0 at Week 12. The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity.

Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Posted

Number

Percentage of participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Primary

Percentage of Participants With Adverse Events

The percentage of participants with serious adverse events and other adverse events is summarized by MedDRA preferred terms and organ classes in the Reported Adverse Events section below.

Safety population: All randomized participants who received at least 1 dose of study drug.

Posted

Number

Percentage of participants

Baseline to the end of study (up to 40 weeks)

ID	Title	Description
OG000	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.
OG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.

Units	Counts
Participants	OG000

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	Placebo	Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.			5	83	41	83
EG001	Omalizumab 300 mg	Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.			18	252	142	252

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina unstable	Cardiac disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected83 at risk EG0010 affected252 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Gastritis erosive	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Hypersensitivity	Immune system disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected83 at risk EG0010 affected252 at risk
Gastroenteritis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Retroperitoneal infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Viral infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Pelvic abscess	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Multiple drug overdose	Injury, poisoning and procedural complications	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Blood glucose increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Blood pressure increased	Investigations	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected83 at risk EG0010 affected252 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Depression	Psychiatric disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected83 at risk EG0010 affected252 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected83 at risk EG0014 affected252 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0001 affected83 at risk EG0012 affected252 at risk
Idiopathic urticaria	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk
Intermittent claudication	Vascular disorders	MedDRA (15.1)	Systematic Assessment	EG0000 affected83 at risk EG0011 affected252 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0005 affected83 at risk EG00115 affected252 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (15.1)	Systematic Assessment	EG0005 affected83 at risk EG00113 affected252 at risk
Sinusitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0009 affected83 at risk EG00131 affected252 at risk
Nasopharyngitis	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0008 affected83 at risk EG00130 affected252 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0004 affected83 at risk EG00129 affected252 at risk
Urinary tract infection	Infections and infestations	MedDRA (15.1)	Systematic Assessment	EG0001 affected83 at risk EG00115 affected252 at risk
Headache	Nervous system disorders	MedDRA (15.1)	Systematic Assessment	EG0006 affected83 at risk EG00127 affected252 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0007 affected83 at risk EG00111 affected252 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (15.1)	Systematic Assessment	EG0005 affected83 at risk EG0013 affected252 at risk
Idiopathic urticaria	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG00010 affected83 at risk EG00137 affected252 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (15.1)	Systematic Assessment	EG0003 affected83 at risk EG00114 affected252 at risk

ID	Term
D000080223	Chronic Urticaria

Ancestor Terms

ID	Term
D014581	Urticaria
D017445	Skin Diseases, Vascular
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D000069444	Omalizumab
D006633	Histamine Antagonists
D020024	Leukotriene Antagonists
D004155	Diphenhydramine

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
D018494	Histamine Agents
D018377	Neurotransmitter Agents
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D045505	Physiological Effects of Drugs
D006727	Hormone Antagonists
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D005021	Ethylamines
D000588	Amines
D009930	Organic Chemicals
D001559	Benzhydryl Compounds
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons