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Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy

Primary Purpose

Idiopathic Angioedema

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Omalizumab
Placebos
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Angioedema focused on measuring Angioedema, Idiopathic Angioedema, IAE

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adults or adolescents who are 18 years or older at the time of screening with physician diagnosis of idiopathic angioedema
  • Minimum of two episodes of idiopathic angioedema in the past 6 months at the time of screening
  • Management of idiopathic angioedema with a stable controller treatment plan for the prior 6 months
  • Complement profile (C1 Esterase inhibitor panel) within normal reference values
  • If a woman is of child-bearing potential, she must agree to a reliable form of birth control including: abstinence, oral contraceptives (birth control pills), Depo-provera, an intrauterine device (IUD), or double-barrier contraception (partner using condom and participant using diaphragm, contraceptive sponge or cervical cap, and spermicidal)

Exclusion Criteria:

  • Diagnosis of Hereditary Angioedema (HAE), Acquired Angioedema, or Ace-inhibitor associated angioedema, which are forms of angioedema with known mechanisms and alternate treatment options
  • Chronic Urticaria (itching and/or hives) with or without Angioedema which are known mast cell mediated processes previously shown to be responsive to the use of omalizumab
  • Previous usage of omalizumab in the last 3 months which can affect the patient-related outcomes and biomarker assessments if not "washed out" of the system
  • Patients, who in the judgment of the investigator, have a history or condition that might compromise patient safety or compliance, interfere with evaluations, or preclude completion of the study

Sites / Locations

  • UW Madison

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Omalizumab

Arm Description

Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection.

Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP.

Outcomes

Primary Outcome Measures

Mean 7-day Angioedema Activity Score (AAS7)
The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.
Presence of a 7-day Angioedema Activity Score (AAS7) Greater Than 0 Across All Treatment Visits
The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.

Secondary Outcome Measures

Mean Angioedema Quality of Life (AE-QoL) Questionnaire
The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.
Mean Angioedema Quality of Life (AE-QoL) Questionnaire Across All Treatment Visits
The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.
Mean Visual Analog Scale
The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.
Presence of Visual Analog Scale Less Than 100 Across All Treatment Visits
The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.
Mean Number of IAE Episodes 2 Weeks Prior to Randomization
Idiopathic angioedema (IAE) refers to episodes of angioedema without urticaria for which no explanation can be found despite a thorough investigation. Patients are sometimes referred to as having IAE while further investigations are being performed, and therefore this term does not necessarily represent a distinct condition, but rather a diagnostic challenge in which the pathway of swelling is yet to be determined.
Number of IAE Events Across All Treatment Visits
Change in Duration of IAE Episodes
Duration of IAE Episodes is participant reported for the 6 months prior to study (baseline) and again at the 6 month time point for the time on study.
Number of Participants Who Visited Urgent Care or Emergency Room
Count of participants who visited urgent care or the emergency room is participant reported. The baseline measure is for the 6 months prior to study, at the 6 month time point for the time on study, and the 9 month time point for the previous 3 months on study.
Number of Participants Who Used Rescue Medication or Corticosteroids
Number of Times Rescue Medications Were Used During the Treatment Period

Full Information

First Posted
November 15, 2016
Last Updated
October 10, 2022
Sponsor
University of Wisconsin, Madison
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02966314
Brief Title
Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy
Official Title
A Phase IV, Randomized, Double-Blind, Placebo-Controlled Exploratory Study of Xolair (Omalizumab) for Treatment of Idiopathic Angioedema in Patients Who Remain Symptomatic Despite Current Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
March 30, 2017 (Actual)
Primary Completion Date
January 6, 2020 (Actual)
Study Completion Date
January 6, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall hospitalizations for a diagnosis of angioedema doubled from the year 2000 to 2009. Although some of the cases represented hereditary angioedema or ace-inhibitor induced angioedema, the majority of episodes were idiopathic. Idiopathic Angioedema (IAE) can be life- threatening especially when affecting tissues within the respiratory tract. No clear guidelines exist for management of this important condition for clinicians. Current therapies typically include avoidance of potential triggers and use of medications either for prophylaxis or for acute events, such as antihistamines, corticosteroids, and epinephrine. There remains a critical need for therapeutic options to provide more effective prophylaxis.
Detailed Description
This study is a randomized, double-blind, placebo-controlled, parallel group trial which will study the effects of omalizumab on patients with 2 or more episodes of Idiopathic Angioedema (IAE) in the past 6 months, despite current therapy. This study has three periods; screening, treatment, and follow-up. Subjects in the screening period will be consented and screened for eligibility criteria. 40 qualified individuals will enter the treatment period. Individuals will be randomized to either monthly subcutaneous administration of omalizumab 300mg (20 subjects) versus monthly placebo injection (20 subjects) in addition to their previously prescribed management plan for a total of 6 months. Individuals will then enter a follow-up period of 4 months. Study visits will occur monthly during the treatment period for update of clinical status and administration of omalizumab/placebo injection. After, the treatment period individuals will be seen twice for follow-up period. The entire study will consist of 10 study visits and will last approx. 10 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Angioedema
Keywords
Angioedema, Idiopathic Angioedema, IAE

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection.
Arm Title
Omalizumab
Arm Type
Active Comparator
Arm Description
Omalizumab is a sterile, white, preservative-free, lyophilized powder, contained in a single-use vial that will be reconstituted with sterile water for injection (SWFI), USP, and administered as a subcutaneous injection. Each omalizumab vial contains 202.5 mg of omalizumab, 145.5 mg sucrose, 2.8 mg L-histidine hydrochloride monohydrate, 1.8 mg L-histidine, and 0.5 mg polysorbate 20. Each vial is designed to deliver 150 mg of omalizumab in 1.2 mL after reconstitution with 1.4 mL SWFI, USP.
Intervention Type
Drug
Intervention Name(s)
Omalizumab
Other Intervention Name(s)
Xolair
Intervention Description
Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
Intervention Type
Drug
Intervention Name(s)
Placebos
Intervention Description
Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.
Primary Outcome Measure Information:
Title
Mean 7-day Angioedema Activity Score (AAS7)
Description
The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.
Time Frame
baseline to end of treatment period at 6 months
Title
Presence of a 7-day Angioedema Activity Score (AAS7) Greater Than 0 Across All Treatment Visits
Description
The AAS7 Score is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.
Time Frame
across all visits during treatment period (up to 6 months)
Secondary Outcome Measure Information:
Title
Mean Angioedema Quality of Life (AE-QoL) Questionnaire
Description
The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.
Time Frame
baseline to end of treatment period at 6 months
Title
Mean Angioedema Quality of Life (AE-QoL) Questionnaire Across All Treatment Visits
Description
The AE-QoL Questionnaire is a 17-item survey, the total possible range of scores is transformed to a scale of 1-100 where higher score indicate increased impairment.
Time Frame
across all visits during treatment period (up to 6 months)
Title
Mean Visual Analog Scale
Description
The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.
Time Frame
baseline to end of treatment period at 6 months
Title
Presence of Visual Analog Scale Less Than 100 Across All Treatment Visits
Description
The effect of treatment compared to placebo on the change in IAE severity from baseline to the end of the treatment period as recorded on a 0-100 visual analog scale. Lower numbers indicate increased severity.
Time Frame
across all visits during treatment period (up to 6 months)
Title
Mean Number of IAE Episodes 2 Weeks Prior to Randomization
Description
Idiopathic angioedema (IAE) refers to episodes of angioedema without urticaria for which no explanation can be found despite a thorough investigation. Patients are sometimes referred to as having IAE while further investigations are being performed, and therefore this term does not necessarily represent a distinct condition, but rather a diagnostic challenge in which the pathway of swelling is yet to be determined.
Time Frame
baseline to end of treatment period at 6 months
Title
Number of IAE Events Across All Treatment Visits
Time Frame
across all visits during treatment period (up to 6 months)
Title
Change in Duration of IAE Episodes
Description
Duration of IAE Episodes is participant reported for the 6 months prior to study (baseline) and again at the 6 month time point for the time on study.
Time Frame
baseline to end of treatment period at 6 months
Title
Number of Participants Who Visited Urgent Care or Emergency Room
Description
Count of participants who visited urgent care or the emergency room is participant reported. The baseline measure is for the 6 months prior to study, at the 6 month time point for the time on study, and the 9 month time point for the previous 3 months on study.
Time Frame
baseline, end of treatment period at 6 months, follow up at 9 months
Title
Number of Participants Who Used Rescue Medication or Corticosteroids
Time Frame
baseline, end of treatment period at 6 months, follow up at 9 months
Title
Number of Times Rescue Medications Were Used During the Treatment Period
Time Frame
up to 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults or adolescents who are 18 years or older at the time of screening with physician diagnosis of idiopathic angioedema Minimum of two episodes of idiopathic angioedema in the past 6 months at the time of screening Management of idiopathic angioedema with a stable controller treatment plan for the prior 6 months Complement profile (C1 Esterase inhibitor panel) within normal reference values If a woman is of child-bearing potential, she must agree to a reliable form of birth control including: abstinence, oral contraceptives (birth control pills), Depo-provera, an intrauterine device (IUD), or double-barrier contraception (partner using condom and participant using diaphragm, contraceptive sponge or cervical cap, and spermicidal) Exclusion Criteria: Diagnosis of Hereditary Angioedema (HAE), Acquired Angioedema, or Ace-inhibitor associated angioedema, which are forms of angioedema with known mechanisms and alternate treatment options Chronic Urticaria (itching and/or hives) with or without Angioedema which are known mast cell mediated processes previously shown to be responsive to the use of omalizumab Previous usage of omalizumab in the last 3 months which can affect the patient-related outcomes and biomarker assessments if not "washed out" of the system Patients, who in the judgment of the investigator, have a history or condition that might compromise patient safety or compliance, interfere with evaluations, or preclude completion of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sameer Mathur, MD/PhD
Organizational Affiliation
UW Madison
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ravi Viswanathan, MD
Organizational Affiliation
UW Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
UW Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35914662
Citation
Goswamy VP, Lee KE, McKernan EM, Fichtinger PS, Mathur SK, Viswanathan RK. Omalizumab for treatment of idiopathic angioedema. Ann Allergy Asthma Immunol. 2022 Nov;129(5):605-611.e1. doi: 10.1016/j.anai.2022.07.017. Epub 2022 Jul 30.
Results Reference
result

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Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy

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