Clinical trial NCT01292473: 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)
Official title: A Phase III, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Evaluate the Efficacy, Response Duration and Safety of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria Who Remain Symptomatic Despite Antihistamine Treatment (H1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Idiopathic Urticaria
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-02-09
Enrollment: 323
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in the Weekly Itch Severity Score at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in the Weekly Urticaria Activity Score (UAS7) at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Weekly Number of Hives Score at Week 12
timeFrame: Baseline, Week 12
measure: Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12
timeFrame: by Week 12
measure: Percentage of Participants With a UAS7 Less Than or Equal to 6 at Week 12
timeFrame: Week 12
measure: Percentage of Weekly Itch Severity Score MID Responders at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Weekly Size of the Largest Hive Score at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Angioedema-free Days From Week 4 to Week 12
timeFrame: Week 4 to Week 12
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Redwood City
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Savannah
country: United States
state: Georgia
city: Woodstock
country: United States
state: Georgia
city: Shiloh
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Overland Park
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Ypsilanti
country: United States
state: Michigan
city: Omaha
country: United States
state: Nebraska
city: Omaha
country: United States
state: Nebraska
city: Brick
country: United States
state: New Jersey
city: Bayside
country: United States
state: New York
city: Bronx
country: United States
state: New York
city: Brooklyn
country: United States
state: New York
city: North Syracuse
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Rockville Centre
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: El Paso
country: United States
state: Texas
city: Sandy
country: United States
state: Utah
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Arhus
country: Denmark
city: Copenhagen
country: Denmark
city: Montpellier
country: France
city: Nice Cedex 3
country: France
city: Paris
country: France
city: Bonn
country: Germany
city: Hannover
country: Germany
city: Leipzig
country: Germany
city: Mainz
country: Germany
city: Muenster
country: Germany
city: München
country: Germany
city: Genova
country: Italy
city: Milano
country: Italy
city: Milano
country: Italy
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Kayseri
country: Turkey
Study officials:
affiliation: Genentech, Inc.
name: Karin E Rosén, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.