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Trial record 3 of 20 for:    omalizumab, urticaria

Mode of Action Study of Omalizumab in Patients With Chronic Idiopathic Urticaria (CIU) Who Fail to Respond to Antihistamine Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01599637
First received: January 25, 2012
Last updated: October 30, 2014
Last verified: October 2014
  Purpose

The study is designed to explore the mode of action for omalizumab therapy in patients with chronic idiopathic urticaria.


Condition Intervention Phase
Chronic Idiopathic Urticaria
Drug: IGE025
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase II, Multi-centre, Randomized, Double Blind, Placebo-controlled Study to Determine the Mode of Action of Omalizumab in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic With Antihistamine Treatment (H1)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Observed Values and Absolute Change From Baseline in FceRI Positive Skin Cells: Dermis, Lesional and Non Lesional Skin [ Time Frame: Baseline through Day 85 post-treatment ] [ Designated as safety issue: No ]
    Observed values and absolute change in FcεRI positive skin cells: dermis non-lesional and lesional. The primary variable for this study was the relative change from baseline in the high affinity IgE receptor (FcεRI) positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment.The values are average of cell numbers derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2

  • Observed Values and Absolute Change From Baseline in IgE Positive Skin Cells: Dermis, Lesional and Non Lesional Skin [ Time Frame: Baseline through Day 85 post-treatment ] [ Designated as safety issue: No ]
    Observed values and absolute change in IgE positive skin cells: dermis non-lesional and lesional The primary variable for this study was the relative change from baseline in IgE positive skin cells, based on skin biopsies collected from patients with CIU after 12 weeks of treatment. The values are average of cell numbers derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2


Secondary Outcome Measures:
  • Correlation of Change From Baseline in IgE Receptor FceRI With Change From Baseline in UAS7 at Week 12 by Treatment, Skin Layer and Lesion Status [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
    Correlation of primary endpoint with The UAS7 which is a composite eDiary−recorded score with numeric severity intensity ratings on a scale of 0−3 (0 = none to 3 = intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch. The daily UAS is the average of the morning and evening scores and the UAS7 is the sum of the daily UAS scores over 7 days.UAS7 score: The sum of the daily UAS scores over 7 days. Range: 0-42. If fewer than 7 but at least 4 daily values were non-missing, the remaining values were imputed to be the average. This is equivalent to multiplying the average of the non missing values by 7. UAS7 score: The sum of the daily UAS scores over 7 days. Range: 0-42. A higher score indicates worse disease.

  • Correlation of Change From Baseline in IgE on Positive Skin Cells With Change From Baseline in UAS7 at Week 12 by Treatment, Skin Layer and Lesion Status [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
    Correlation of primary endpoint with The UAS7 which is a composite eDiary−recorded score with numeric severity intensity ratings on a scale of 0−3 (0 = none to 3 = intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch. The daily UAS is the average of the morning and evening scores and the UAS7 is the sum of the daily UAS scores over 7 days.UAS7 score: The sum of the daily UAS scores over 7 days. Range: 0-42. If fewer than 7 but at least 4 daily values were non-missing, the remaining values were imputed to be the average. This is equivalent to multiplying the average of the non missing values by 7. UAS7 score: The sum of the daily UAS scores over 7 days. Range: 0-42. A higher score indicates worse disease.

  • Observed Values and Absolute Change From Baseline in Skin Cell Subsets (CD3, CD4, CD8, Eosinophils, DCs, and Mast Cells) by Parameter, Skin Layer, Lesion Status, Treatment and Visit [ Time Frame: Baseline to Day 85 ] [ Designated as safety issue: No ]
    The average number of cells derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2

  • Observed Values From Baseline Through End of Study of Serum Chemkines or Histamine in Peripheral Blood Cells by Parameter, Treatment and Visit [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
  • Observed Values and Change From Baseline in Peripheral Blood Cell Subsets (FACS Parameters) at Week 12 (Day 85) by Treatment (PD Analysis Set) Measured as % Out of Leukocytes. [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
    Fluorescence-activated cell sorting (FACS) is a specialized type of flow cytometry that provides a method for sorting a heterogeneous mixture of biological cells into two or more containers, one cell at a time, based upon the specific light scattering and fluorescent characteristics of each cell. (FACS) provides fast, objective and quantitative recording of fluorescent signals from individual cells as well as physical separation of cells of particular interest. A wide range of fluorophores can be used as labels in flow cytometry. Fluorophores are typically attached to an antibody that recognizes a target feature on or in the cell; they may also be attached to a chemical entity with affinity for the cell membrane or another cellular structure. Each fluorophore has a characteristic peak excitation and emission wavelength.

  • Observed Values and Change From Baseline in Peripheral Blood Cell Subsets (FACS Parameters) at Week 12 (Day 85) by Treatment (PD Analysis Set) Measured in Fluorescence Units. [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
    Fluorescence-activated cell sorting (FACS) is a specialized type of flow cytometry that provides a method for sorting a heterogeneous mixture of biological cells into two or more containers, one cell at a time, based upon the specific light scattering and fluorescent characteristics of each cell. (FACS) provides fast, objective and quantitative recording of fluorescent signals from individual cells as well as physical separation of cells of particular interest. A wide range of fluorophores can be used as labels in flow cytometry. Fluorophores are typically attached to an antibody that recognizes a target feature on or in the cell; they may also be attached to a chemical entity with affinity for the cell membrane or another cellular structure. Each fluorophore has a characteristic peak excitation and emission wavelength.

  • Comparison of Baseline PD Parameters Between Healthy Volunteers and Urticaria Patients by Skin Layer Pharmacodynamic Analysis Set [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    The # positive cell values are average of cell numbers derived from counting 5 consecutive microscopic fields. Area counted is 5x 0.196 mm2

  • Serum Levels of Omalizumab [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
    Serum concentrations (ng/mL) of omalizumab by visit after the administration of omalizumab 300 mg every 4 weeks

  • Mean (SD) Serum Total IgE Concentration From Baseline by Visit [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
  • Mean (SD) Serum Total IgE % Change From Baseline by Visit [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
  • Mean (SD) Serum Free IgE Concentration From Baseline by Visit [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
  • Mean (SD) Serum Free IgE % Change From Baseline by Visit [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
  • Summary Statistics of Observed Values and Absolute Change From Baseline in Specific IgE Against Allergens and Bacterial Antigens by Parameter, Treatment and Visit [ Time Frame: Baseline through Day 140 ] [ Designated as safety issue: No ]
  • Change From Baseline in Urticaria Activity Score (UAS7) [ Time Frame: Baseline, Day 85 ] [ Designated as safety issue: No ]
    Efficacy was assessed by the urticaria activity score (UAS). UAS was completed each morning and evening on a daily basis to record patient symptoms of itch and hives via an electronic diary. The UAS is a composite eDiary−recorded score with numeric severity intensity ratings on a scale of 0−3 (0 = none to 3 = intense/severe) for 1) the number of wheals (hives); and 2) the intensity of the itch. The daily UAS is the average of the morning and evening scores and the UAS7 is the sum of the daily UAS scores over 7 days.UAS7 score: The sum of the daily UAS scores over 7 days. Range: 0-42. If fewer than 7 but at least 4 daily values were non-missing, the remaining values were imputed to be the average. This is equivalent to multiplying the average of the non missing values by 7. UAS7 score: The sum of the daily UAS scores over 7 days. Range: 0-42. A higher score indicates worse disease. A negative change score (Week 12 score minus Baseline score) indicates improvement.

  • Likert Scale-Physician's and Patients In-clinic Global Assessment by Treatment [ Time Frame: Baseline, Day 85 ] [ Designated as safety issue: No ]
    The investigator or the person he or she designated and the patient provided scoring of the patient's global assessment of symptoms (urticaria lesions (hives) and pruritus) reflective of the patient's condition over the 12 hours prior to the visit (0 = no symptoms, 1 = mild, 2 = moderate 3 = severe

  • Percentage of Angioedema-free Days Weeks 4 Through 12 by Treatment [ Time Frame: Day 29 to Day 85 ] [ Designated as safety issue: No ]
  • Change From Baseline in Dermatology Life Quality Index (DLQI) by Treatment [ Time Frame: Baseline through Day 85 ] [ Designated as safety issue: No ]
    The DLQI is a 10-item dermatology-specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives. An overall score was calculated as well as for the following domains: Symptoms and Feelings, Daily Activities, Leisure, Work and School, Personal Relationships, Treatment.Negative score shows positive efficacy. Meaning of DLQI Scores 0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. The DLQI can also be expressed as a percentage of the maximum possible score of 30.

  • Skindex-29 by Treatment [ Time Frame: Baseline and Day 85 ] [ Designated as safety issue: No ]
    The Skindex-29 is a validated 29-item instrument to measure the effects of skin disease on patients' quality of life.Results are reported as 3 scale scores (functioning, emotions and symptoms) and a composite score (average scale score). The domain scores and the overall score are expressed on a 100-point scale, with higher scores indicating a lower level of quality of life. The cuttoff values for each category are noted below. Symtoms; 39 mild, 42 moderate,52 severe. Emotions; 24 mild, 35 moderate, 39 severe. Functioning: 21 mild, 32 moderate, 37 severe. Overal Score: 25 mild, 32 moderate, 44 severe.

  • Chronic Urticaria Quality of Life Questionnaire (Cu-Q2OL) by Treatment [ Time Frame: Baseline and Day 85 ] [ Designated as safety issue: No ]
    The Cu-Q2OL is a 23-item CIU-specific health-related quality of life questionnaire. Patients rated their CIU symptoms and the impact of their CIU on various aspects of their lives. An overall score was calculated as well for the following domains: pruritus, swelling, impact on life activities, sleep problems, limits, and looks. Zero is the minmum score and 100 the maximum score. The higher score correlates to more disease activity.


Enrollment: 40
Study Start Date: April 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IGE025
Patients will receive omalizumab administered subcutaneously every 4 weeks at the study center.
Drug: IGE025
Study medication will be supplied as a lyophilized, sterile powder in a single-use, 5-mL vial.
Placebo Comparator: Placebo to IGE025
Placebo administered subcutaneously every 4 weeks at the study center.
Drug: placebo
Study medication will be supplied as a lyophilized, sterile powder in a single-use, 5-mL vial.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of chronic spontaneous urticaria refractory to H1 antihistamines at Baseline

Exclusion Criteria:

  • Clearly defined underlying etiology for chronic urticarias other than CIU (main manifestation being physical urticaria). This includes the following urticarias: Acute, solar, cholinergic, heat, cold, aquagenic, delayed pressure or contact, as well as the following diseases as these diseases may have symptoms of urticaria or angioedema: Urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, or generalized cancer.
  • Previous treatment with omalizumab.
  • A history or presence of atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or other skin disease associated with itch.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01599637

Locations
Germany
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Dresden, Germany, 01307
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Muenster, Germany, 48149
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01599637     History of Changes
Other Study ID Numbers: CIGE025E2201, 2011-004216-31
Study First Received: January 25, 2012
Results First Received: September 10, 2014
Last Updated: October 30, 2014
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut

Keywords provided by Novartis:
Chronic idiopathic urticaria
CIU
Xolair
IGE025
FcεRI
IgE

Additional relevant MeSH terms:
Urticaria
Omalizumab
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Skin Diseases
Skin Diseases, Vascular
Histamine Antagonists
Histamine H1 Antagonists
Anti-Allergic Agents
Anti-Asthmatic Agents
Histamine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014