Clinical trial NCT01287117: A Study of the Efficacy and Safety of Omalizumab (Xolair) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Antihistamine (H1) Treatment
Official title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy and Safety of Xolair® (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (CSU) 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: 2011-02-01
Enrollment: 319
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-dose H1 antihistamine treatment.

Detailed description: Type I Error Rate Control Plan

Primary Outcome Measure

In order to maintain an overall type I error rate of 0.05 (2-sided) across the 3 omalizumab dose levels, the testing of the primary Outcome Measure was conducted in the following hierarchical order. A p-value \< 0.05 is only considered statistically significant if statistical significance was 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

Secondary Outcome Measures

A hierarchical analysis of the following secondary Outcome Measures was performed for each dose found to be significant in the primary Outcome Measure. A p-value \< 0.05 is only considered statistically significant if statistical significance was claimed at the previous stage.

* Stage 1: Change from baseline to Week 12 in the urticaria activity score over 7 days (UAS7)
* Stage 2: Change from Baseline to Week 12 in the weekly number of hives score
* Stage 3: Time to minimally important difference (MID) response in the weekly itch severity score by Week 12
* Stage 4: Percentage of participants with a UAS7 score ≤ 6 at Week 12
* Stage 5: Percentage of weekly itch severity score MID responders at Week 12
* Stage 6: Change from Baseline to Week 12 in the weekly size of the largest hive score
* Stage 7: Change from Baseline in the overall dermatology life quality index (DLQI) score at Week 12
* Stage 8: Change from Baseline in the overall dermatology life quality index (DLQI) score at Week 12
* Stage 9: Percentage of complete responders (UAS7 = 0) at Week 12

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Chronic Idiopathic Urticaria (CIU)/Chronic Spontaneous Urticaria (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 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 to Week 12 in the Weekly Itch Severity Score
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7)
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Weekly Number of Hives Score
timeFrame: Baseline to Week 12
measure: Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12
timeFrame: Baseline to Week 12
measure: Percentage of Participants With a UAS7 Score ≤ 6 at Week 12
timeFrame: Week 12
measure: Percentage of Weekly Itch Severity Score MID Responders at Week 12
timeFrame: Baseline to Week 12
measure: Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score
timeFrame: Baseline to Week 12
measure: Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12
timeFrame: Baseline to Week 12
measure: Percentage of Angioedema-free Days From Week 4 to Week 12
timeFrame: Week 4 to Week 12
measure: Percentage of Complete Responders (UAS7 = 0) at Week 12
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntington Beach
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Palmdale
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Jose
country: United States
state: California
city: Studio City
country: United States
state: California
city: Centennial
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Coral Gables
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tallahassee
country: United States
state: Florida
city: Columbus
country: United States
state: Georgia
city: Springfield
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Burlington
country: United States
state: Massachusetts
city: St Louis
country: United States
state: Missouri
city: Edison
country: United States
state: New Jersey
city: Skillman
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Upland
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Sandy
country: United States
state: Utah
city: Springfield
country: United States
state: Virginia
city: Lacrosse
country: United States
state: Wisconsin
city: Madison
country: United States
state: Wisconsin
city: København
country: Denmark
city: Odense
country: Denmark
city: Bordeaux
country: France
city: Marseille
country: France
city: Reims
country: France
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Dresden
country: Germany
city: Freiburg
country: Germany
city: Heidelberg
country: Germany
city: Muenchen
country: Germany
city: Muenster
country: Germany
city: Perugia
country: Italy
city: Roma
country: Italy
city: Terni
country: Italy
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Wroclaw
country: Poland
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Pamplona
country: Spain
city: Ankara
country: Turkey
city: Bursa
country: Turkey
city: Istanbul
country: Turkey
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
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: Saini SS, Bindslev-Jensen C, Maurer M, Grob JJ, Bulbul Baskan E, Bradley MS, Canvin J, Rahmaoui A, Georgiou P, Alpan O, Spector S, Rosen K. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study. J Invest Dermatol. 2015 Jan;135(1):67-75. doi: 10.1038/jid.2014.306. Epub 2014 Jul 21.