Clinical trial NCT01264939: 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
Official title: A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Idiopathic Urticaria
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2010-12-22
Enrollment: 336
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 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).


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.

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline to the end of study (up to 40 weeks)
Secondary outcomes:
measure: Change From Baseline to Week 12 in the Weekly Itch Severity Score
timeFrame: Baseline to Week 12
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: Scottsdale
country: United States
state: Arizona
city: Mission Viejo
country: United States
state: California
city: Napa
country: United States
state: California
city: Orange
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Miami
country: United States
state: Florida
city: North Palm Beach
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Savannah
country: United States
state: Georgia
city: Evansville
country: United States
state: Indiana
city: Iowa City
country: United States
state: Iowa
city: Crescent Springs
country: United States
state: Kentucky
city: Owensboro
country: United States
state: Kentucky
city: Wheaton
country: United States
state: Maryland
city: Brookline
country: United States
state: Massachusetts
city: Brookline
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Bozeman
country: United States
state: Montana
city: Missoula
country: United States
state: Montana
city: Brick
country: United States
state: New Jersey
city: Mineola
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: High Point
country: United States
state: North Carolina
city: Sylvania
country: United States
state: Ohio
city: Lake Oswego
country: United States
state: Oregon
city: Altoona
country: United States
state: Pennsylvania
city: Blue Bell
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Katy
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Draper
country: United States
state: Utah
city: South Burlington
country: United States
state: Vermont
city: Richmond
country: United States
state: Virginia
city: Canberra
country: Australia
state: Australian Capital Territory
city: Brisbane
country: Australia
state: Queensland
city: Carlton
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Koeln
country: Germany
city: Lübeck
country: Germany
city: Mainz
country: Germany
city: Marburg
country: Germany
city: Tübingen
country: Germany
city: Auckland
country: New Zealand
city: Beckenham
country: New Zealand
city: Tauranga
country: New Zealand
city: Wellington
country: New Zealand
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lodz
country: Poland
city: Warszawa
country: Poland
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Aarau
country: Switzerland
city: Bern
country: Switzerland
city: St. Gallen
country: Switzerland
city: Cambridge
country: United Kingdom
city: Leicester
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Norwich
country: United Kingdom
city: Oxford
country: United Kingdom
city: Sheffield
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: Edward R. Conner, M.D.
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.