A Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine Treatment (H1)

NCT ID: NCT01292473

Last Updated: 2013-10-11

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

323 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2012-06-30

Brief Summary

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The study is a global Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of omalizumab administered subcutaneously as an add-on therapy for the treatment of adolescent and adult patients aged 12-75 who have been diagnosed with refractory CIU and who remain symptomatic despite standard-dosed H1 antihistamine treatment.

Detailed Description

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The trial incorporated a Type I error control plan, as follows:

The testing of the primary endpoint was conducted in the following hierarchical order. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been claimed at the previous stage.

* Stage 1: Omalizumab 300-mg group vs. placebo
* Stage 2: Omalizumab 150-mg group vs. placebo
* Stage 3: Omalizumab 75-mg group vs. placebo

A hierarchical analysis of the secondary endpoints was performed for each dose found to be significant in the primary endpoint. A p-value that is less than 0.05 can only be claimed statistically significant if statistical significance has been claimed at the previous stage.

* Stage 1: Change from baseline in Urticaria Activity Score (UAS7) at Week 12
* Stage 2: Change from baseline in the weekly number of hives score at Week 12
* Stage 3: Time to weekly itch severity score Minimally Important Difference (MID) response at Week 12
* Stage 4: Proportion of patients with UAS7 ≤ 6 at Week 12
* Stage 5: Proportion of weekly itch severity score MID Responders at Week 12
* Stage 6: Change from baseline in weekly size of the largest hive score at Week 12
* Stage 7: Change from baseline in overall Dermatology Life Quality Index (DLQI) score at Week 12
* Stage 8: Proportion of angioedema-free days from Week 4 to Week 12

Conditions

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Chronic Idiopathic Urticaria

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Placebo

Placebo subcutaneously (sc) every 4 weeks

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo was supplied lyophilized in vials.

Omalizumab

Intervention Type DRUG

Omalizumab was supplied lyophilized in vials.

Omalizumab 75 mg

Omalizumab 75 mg sc every 4 weeks

Group Type EXPERIMENTAL

Omalizumab

Intervention Type DRUG

Omalizumab was supplied lyophilized in vials.

Omalizumab 150 mg

Omalizumab 150 mg sc every 4 weeks

Group Type EXPERIMENTAL

Omalizumab

Intervention Type DRUG

Omalizumab was supplied lyophilized in vials.

Omalizumab 300 mg

Omalizumab 300 mg sc every 4 weeks.

Group Type EXPERIMENTAL

Omalizumab

Intervention Type DRUG

Omalizumab was supplied lyophilized in vials.

Interventions

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Placebo

Placebo was supplied lyophilized in vials.

Intervention Type DRUG

Omalizumab

Omalizumab was supplied lyophilized in vials.

Intervention Type DRUG

Other Intervention Names

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Xolair

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) CIU/CSU refractory to H1 antihistamines at the time of randomization.

Exclusion Criteria

* Treatment with an investigational agent within 30 days prior to screening.
* Weight \< 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.
* Any H2 antihistamine use within 7 days prior to screening.
* Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to screening.
* Any H1 antihistamines at greater than approved doses within 3 days 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.
* Nursing women or women of childbearing potential, unless they meet the following definition of post-menopausal: 12 months of natural amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels \> 40 milli-international units per milliliter (mIU/mL) or 6 weeks post surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy or are using one or more of the following acceptable methods of contraception: surgical sterilization, hormonal contraception, and double-barrier methods.
Minimum Eligible Age

12 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Karin E Rosén, MD, PhD

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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La Jolla, California, United States

Site Status

Los Angeles, California, United States

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Redwood City, California, United States

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Walnut Creek, California, United States

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Denver, Colorado, United States

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Miami, Florida, United States

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Savannah, Georgia, United States

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Woodstock, Georgia, United States

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Shiloh, Illinois, United States

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Indianapolis, Indiana, United States

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Overland Park, Kansas, United States

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Baltimore, Maryland, United States

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Wheaton, Maryland, United States

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Ypsilanti, Michigan, United States

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Omaha, Nebraska, United States

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Omaha, Nebraska, United States

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Brick, New Jersey, United States

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Bayside, New York, United States

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Brooklyn, New York, United States

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North Syracuse, New York, United States

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Rochester, New York, United States

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Rockville Centre, New York, United States

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The Bronx, New York, United States

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Asheville, North Carolina, United States

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Canton, Ohio, United States

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Cincinnati, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Providence, Rhode Island, United States

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El Paso, Texas, United States

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Sandy City, Utah, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Madison, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Aarhus, , Denmark

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Copenhagen, , Denmark

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Montpellier, , France

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Nice, , France

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Paris, , France

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Bonn, , Germany

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Hanover, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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München, , Germany

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Münster, , Germany

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Genova, , Italy

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Milan, , Italy

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Milan, , Italy

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Gdansk, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Barcelona, , Spain

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Madrid, , Spain

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

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Countries

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Russia United States Denmark France Germany Italy Poland Spain Turkey (Türkiye)

References

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Casale TB, Trzaskoma B, Holden M, Bernstein JA, Maurer M. Does angioedema in patients with chronic spontaneous urticaria impact response to omalizumab? World Allergy Organ J. 2024 Aug 5;17(8):100943. doi: 10.1016/j.waojou.2024.100943. eCollection 2024 Aug.

Reference Type DERIVED
PMID: 39193419 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29655772 (View on PubMed)

Goldstein S, Gabriel S, Kianifard F, Ortiz B, Skoner DP. Clinical features of adolescents with chronic idiopathic or spontaneous urticaria: Review of omalizumab clinical trials. Ann Allergy Asthma Immunol. 2017 Apr;118(4):500-504. doi: 10.1016/j.anai.2017.02.003.

Reference Type DERIVED
PMID: 28390587 (View on PubMed)

Saini SS, Omachi TA, Trzaskoma B, Hulter HN, Rosen K, Sterba PM, Courneya JP, Lackey A, Chen H. Effect of Omalizumab on Blood Basophil Counts in Patients with Chronic Idiopathic/Spontaneous Urticaria. J Invest Dermatol. 2017 Apr;137(4):958-961. doi: 10.1016/j.jid.2016.11.025. Epub 2016 Dec 6. No abstract available.

Reference Type DERIVED
PMID: 27939380 (View on PubMed)

Gimenez-Arnau AM, Spector S, Antonova E, Trzaskoma B, Rosen K, Omachi TA, Stull D, Balp MM, Murphy T. Improvement of sleep in patients with chronic idiopathic/spontaneous urticaria treated with omalizumab: results of three randomized, double-blind, placebo-controlled studies. Clin Transl Allergy. 2016 Aug 18;6:32. doi: 10.1186/s13601-016-0120-0. eCollection 2016.

Reference Type DERIVED
PMID: 27540466 (View on PubMed)

Zazzali JL, Kaplan A, Maurer M, Raimundo K, Trzaskoma B, Solari PG, Antonova E, Mendelson M, Rosen KE. Angioedema in the omalizumab chronic idiopathic/spontaneous urticaria pivotal studies. Ann Allergy Asthma Immunol. 2016 Oct;117(4):370-377.e1. doi: 10.1016/j.anai.2016.06.024. Epub 2016 Jul 14.

Reference Type DERIVED
PMID: 27424128 (View on PubMed)

Casale TB, Bernstein JA, Maurer M, Saini SS, Trzaskoma B, Chen H, Grattan CE, Gimenez-Arnau A, Kaplan AP, Rosen K. Similar Efficacy with Omalizumab in Chronic Idiopathic/Spontaneous Urticaria Despite Different Background Therapy. J Allergy Clin Immunol Pract. 2015 Sep-Oct;3(5):743-50.e1. doi: 10.1016/j.jaip.2015.04.015. Epub 2015 Jun 6.

Reference Type DERIVED
PMID: 26054553 (View on PubMed)

Maurer M, Rosen K, Hsieh HJ, Saini S, Grattan C, Gimenez-Arnau A, Agarwal S, Doyle R, Canvin J, Kaplan A, Casale T. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013 Mar 7;368(10):924-35. doi: 10.1056/NEJMoa1215372. Epub 2013 Feb 24.

Reference Type DERIVED
PMID: 23432142 (View on PubMed)

Other Identifiers

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Q4882g

Identifier Type: -

Identifier Source: org_study_id