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A Study of the Efficacy and Safety of Omalizumab Through 48 Weeks in Participants With Chronic Idiopathic Urticaria

Phase 4
Completed
Conditions
Urticaria
Interventions
Drug: Placebo
Registration Number
NCT02392624
Lead Sponsor
Genentech, Inc.
Brief Summary

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of subcutaneous (SC) omalizumab (Xolair) as an add-on therapy through 48 weeks for treatment of H1 antihistamine refractory chronic idiopathic urticaria (CIU). After completing an initial 24-week open-label treatment period with omalizumab 300 milligrams (mg) every 4 weeks (Q4W), participants responding to omalizumab will be randomized at a 3:2 ratio (omalizumab:placebo) to either continue omalizumab or be transitioned to placebo for a further 24 weeks.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
206
Inclusion Criteria
  • Diagnosis of CIU refractory to H1 antihistamines at baseline
  • Presence of itch and hives for at least 8 consecutive weeks at any time prior to enrollment despite current use of H1 antihistamine treatment (up to four times the approved dose) during this time period
  • UAS7 score (range 0-42) ≥ 16 and itch component of UAS7 (range 0-21) ≥ 8 during 7 days prior to baseline
  • Participants must have been on a non-sedating H1 antihistamine treatment (up to four times the approved dose) for CIU for at least 3 consecutive days immediately prior to screening visit with continued current use on the day of the initial screening visit
  • CIU diagnosis for ≥ 6 months
  • Willing and able to complete a daily symptom eDiary for the duration of the study
Exclusion Criteria
  • Treatment with an investigational agent within 30 days of the initial screening visit
  • Body weight less than 20 kilograms
  • Clearly defined underlying etiology for chronic urticarias other than CIU
  • Evidence of a parasitic infection
  • Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or other skin disease associated with itch
  • Previous treatment with omalizumab within 1 year prior to the initial screening visit
  • Participants may not have taken during treatment period or have been taking within 30 days before the initial screening visit any of the following medications or treatments:

regular (daily/every other day during 5 or more consecutive days) systemic corticosteroids, hydroxychloroquine, methotrexate, mycophenolate, cyclosporine, cyclophosphamide, intravenous immunoglobulin G or plasmapheresis

  • Regular (daily/every other day) oral doxepin use within 14 days prior to the initial screening visit
  • Pregnant or lactating women, or women intending to become pregnant during the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will receive open-label omalizumab treatment at 300 mg SC Q4W for 24 weeks. After 24 weeks open-label treatment, eligible participants will be randomized to receive placebo SC Q4W for next 24 weeks (up to Week 48). Participants randomized to placebo may, at the discretion of the investigator, be transitioned from blinded study drug to open-label omalizumab at 300 mg SC Q4W if they experience clinically significant worsening in their CIU (as judged by the investigator). Participants who are transitioned to open-label omalizumab will continue to receive open-label omalizumab as study drug until Week 48.
OmalizumabOmalizumabParticipants will receive open-label omalizumab treatment at 300 mg SC Q4W for 24 weeks. After 24 weeks open-label treatment, eligible participants will be randomized to receive omalizumab treatment at 300 mg SC Q4W for next 24 weeks (up to Week 48). Participants randomized to omalizumab may, at the discretion of the investigator, be transitioned from blinded study drug to open-label omalizumab at 300 mg SC Q4W if they experience clinically significant worsening in their CIU (as judged by the investigator). Participants who are transitioned to open-label omalizumab will continue to receive open-label omalizumab as study drug until Week 48.
PlaceboOmalizumabParticipants will receive open-label omalizumab treatment at 300 mg SC Q4W for 24 weeks. After 24 weeks open-label treatment, eligible participants will be randomized to receive placebo SC Q4W for next 24 weeks (up to Week 48). Participants randomized to placebo may, at the discretion of the investigator, be transitioned from blinded study drug to open-label omalizumab at 300 mg SC Q4W if they experience clinically significant worsening in their CIU (as judged by the investigator). Participants who are transitioned to open-label omalizumab will continue to receive open-label omalizumab as study drug until Week 48.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Experienced Clinical Worsening in CIU as Assessed by Urticaria Activity Score Over 7 Days (UAS7) (Clinical Worsening: UAS7 Greater Than or Equal to [>/=] 12, Maintained for At Least 2 Consecutive Weeks)From randomization (Week 24) to Week 48

Urticaria activity score (UAS) is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals (hives) per 24 hours and the intensity of the pruritus (itch). The total UAS score (sum of the wheal and pruritus scores) ranges from 0 to 6. Due to variations in chronic urticaria disease intensity, assessment of disease activity was based on a weekly (7 days) UAS score called UAS7, that is, the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. Clinical worsening in CIU was defined as UAS7 \>/=12 for at least 2 consecutive weeks post-randomization between Weeks 24 and 48.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Experienced Clinical Worsening in CIU as Assessed by UAS7 (Clinical Worsening: UAS7 Greater Than [>] 6, Maintained for At Least 2 Consecutive Weeks)From randomization (Week 24) to Week 48

The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. Clinical worsening in CIU was defined as UAS7 \>6 for at least 2 consecutive weeks post-randomization between weeks 24 and 48.

Retreatment Efficacy: Change From Time of Retreatment to 12 Weeks After Retreatment in UAS7 Among Participants Randomized to Placebo and Who Were Retreated With Open-Label Omalizumab After RandomizationAt start of retreatment (any time between Weeks 24 and Week 48) and 12 weeks after retreatment (up to Week 60)

The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change in score indicates improvement.

Time to Clinical Worsening in CIU as Assessed by UAS7 (Clinical Worsening: UAS7 >/=12, Maintained for At Least 2 Consecutive Weeks)From randomization (Week 24) to Week 48

The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. Time to clinical worsening in CIU was defined as the number of weeks from the first double-blind treatment to the first two-week interval with UAS7 \>/=12 for both weeks. If clinical worsening did not occur, time to clinical worsening was censored at the end of the last week for which the UAS7 score was not missing and less than (\<) 12, prior to last randomized dose + 4 weeks, or the first open-label transition dose, whichever was earlier. Median time to clinical worsening was estimated using Kaplan-Meier analysis and corresponding 95% confidence interval (CI) was computed using the method of Brookmeyer and Crowley.

Change From Randomization (Week 24) to Week 48 in UAS7 Among Participants Who Received Total 48 Weeks Treatment With OmalizumabWeek 24 (randomization) and Week 48

The UAS is a composite diary-recorded score with numeric severity ratings (0=none to 3=intense) for the number of wheals per 24 hours and the intensity of the pruritus. The total UAS score ranges from 0 to 6. UAS7 is the sum of the daily average UASs (average of morning and evening scores), ranging from 0 to 42 per week. A higher score indicates worse disease. A negative change in score (Week 48 score minus Week 24 score) indicates improvement.

Trial Locations

Locations (40)

Allergy and Asthma Relief Experts

🇺🇸

Granada Hills, California, United States

Allergy & Asthma Care Center of Southern California

🇺🇸

Long Beach, California, United States

Dermatology Research Associate

🇺🇸

Los Angeles, California, United States

Southern California Research Center

🇺🇸

Mission Viejo, California, United States

Choc Psf, Amc

🇺🇸

Orange, California, United States

Allergy & Asthma Consultants

🇺🇸

Redwood City, California, United States

Allergy and Asthma Clinical Research, Inc.

🇺🇸

Walnut Creek, California, United States

IMMUNOe Research Centers

🇺🇸

Centennial, Colorado, United States

Colorado Allergy & Asthma Centers, Pc

🇺🇸

Denver, Colorado, United States

Florida Center for Allergy and Asthma Research

🇺🇸

Aventura, Florida, United States

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Allergy and Asthma Relief Experts
🇺🇸Granada Hills, California, United States

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