A Safety Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic Despite Treatment With H1 Antihistamines, H2 Blockers, and/or Leukotriene Receptor Antagonists

NCT01264939 | Completed Phase 3 Results

• 2 other identifiers: Q4883gGA00889
• Study Type: interventional
• Target: 336
• Locations: 8 countries
• Sites: 73

Brief Summary

The study is a global Phase III, multicenter, randomized, double-blind, placebo controlled, parallel-group study to evaluate the safety and efficacy 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 chronic idiopathic urticaria (CIU) who remain symptomatic despite standard-dosed H1 antihistamine treatment (including doses up to 4 times above the approved dose level), H2 blockers, and/or leukotriene receptor antagonists (LTRA).

Conditions

Chronic Idiopathic Urticaria

Outcome Measures

Primary Outcomes (1)

• 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 (10)

• Change From Baseline to Week 12 in the Weekly Itch Severity Score

  Baseline to Week 12

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

  Baseline to Week 12

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

  Baseline to Week 12

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

  Baseline to Week 12

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

  Week 12

Study Arms (2)

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

Interventions

Omalizumab DRUG

Omalizumab was supplied as a lyophilized, sterile powder in a single-use vial.

Also known as: Xolair

Omalizumab 300 mg

Placebo DRUG

Placebo was supplied as a lyophilized, sterile powder in a single-use vial without study drug.

Placebo

H1 antihistamine, H2 antihistamine, leukotriene receptor antagonist DRUG

Participants were required to maintain stable doses of their pre-randomization combination therapy with an H1 antihistamine and either an H2 blocker or leukotriene receptor antagonist, or all 3 drugs in combination, throughout the 24-week treatment period and 16-week follow-up period of the 40-week study.

Omalizumab 300 mg; Placebo

Diphenhydramine DRUG

Participants were provided with diphenhydramine 25 mg for itch relief on an as-needed basis, up to a maximum of 3 doses within 24 hours for the duration of the 40-week study.

Omalizumab 300 mg; Placebo

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (73)

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Scottsdale, Arizona, 85251, United States

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Mission Viejo, California, 92691, United States

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Napa, California, 94558, United States

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Orange, California, 92868, United States

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Sacramento, California, 95819, United States

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San Diego, California, 92120, United States

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Miami, Florida, 33173, United States

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North Palm Beach, Florida, 33408, United States

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Tampa, Florida, 33613, United States

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Savannah, Georgia, 31406, United States

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Evansville, Indiana, 47713, United States

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Iowa City, Iowa, 52242, United States

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Crescent Springs, Kentucky, 41017, United States

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Owensboro, Kentucky, 42301, United States

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Wheaton, Maryland, 20902, United States

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Brookline, Massachusetts, 02445, United States

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Brookline, Massachusetts, 2167, United States

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Ann Arbor, Michigan, 48106, United States

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Minneapolis, Minnesota, 55402, United States

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Rochester, Minnesota, 55901, United States

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Bozeman, Montana, 59718, United States

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Missoula, Montana, 59808, United States

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Brick, New Jersey, 8724, United States

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Mineola, New York, 11501, United States

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Rochester, New York, 14618, United States

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High Point, North Carolina, 27262, United States

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Sylvania, Ohio, 43560, United States

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Lake Oswego, Oregon, 97035, United States

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Altoona, Pennsylvania, 16601, United States

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Blue Bell, Pennsylvania, 19422, United States

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Hershey, Pennsylvania, 17033, United States

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Charleston, South Carolina, 29407, United States

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Knoxville, Tennessee, 37909, United States

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Dallas, Texas, 75230, United States

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Katy, Texas, 77450, United States

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San Antonio, Texas, 78233, United States

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San Antonio, Texas, 78251, United States

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Draper, Utah, 84020, United States

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South Burlington, Vermont, 05403, United States

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Richmond, Virginia, 23298, United States

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Canberra, Australian Capital Territory, 2605, Australia

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Brisbane, Queensland, 4102, Australia

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Carlton, Victoria, 3053, Australia

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Melbourne, Victoria, 3004, Australia

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Berlin, 10117, Germany

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Cologne, 50937, Germany

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Erlangen, 91054, Germany

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Freiburg im Breisgau, 79104, Germany

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Hamburg, 20354, Germany

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Lübeck, 23538, Germany

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Mainz, 55131, Germany

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Marburg, 35033, Germany

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Tübingen, 72076, Germany

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Auckland, 1023, New Zealand

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Beckenham, 8024, New Zealand

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Tauranga, 3110, New Zealand

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Wellington, 6002, New Zealand

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Krakow, 31-023, Poland

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Lodz, 90-153, Poland

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Lodz, 92-213, Poland

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Warsaw, 01-817, Poland

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Singapore, 119074, Singapore

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Singapore, 529889, Singapore

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Aarau, 5001, Switzerland

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Bern, 3000, Switzerland

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Sankt Gallen, 9007, Switzerland

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Cambridge, CB2 2QQ, United Kingdom

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Leicester, LE3 9QP, United Kingdom

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London, E11 1NR, United Kingdom

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London, EC1M 6BQ, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Oxford, OX3 7LJ, United Kingdom

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Sheffield, S5 7AU, United Kingdom

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Related Publications (6)

• 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.

  PMID: 29655772 DERIVED

• 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.

  PMID: 28390587 DERIVED

• 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.

  PMID: 27939380 DERIVED

• 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.

  PMID: 27540466 DERIVED

• 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.

  PMID: 27424128 DERIVED

• 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.

  PMID: 26054553 DERIVED

MeSH Terms

Conditions

Chronic Urticaria

Interventions

Omalizumab; Histamine Antagonists; Leukotriene Antagonists; Diphenhydramine

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins; Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Ethylamines; Amines; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

800 821-8590

Study Officials

• Edward R. Conner, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2010
• First Posted: December 22, 2010
• Study Start: February 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 26, 2013
• Results First Posted: November 26, 2013

Record last verified: 2013-09

Locations

AU (4); US (40); CH (3); PL (4); DE (9); NZ (4); SG (2); GB (7)