Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy

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

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Angioedema
• Intervention / Treatment: Drug: Placebos; Drug: Omalizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection.	Drug: Placebos; Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.
Active Comparator: Omalizumab; 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.	Drug: Omalizumab; Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.; Other Names: Xolair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to end of treatment period at 6 months
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.	across all visits during treatment period (up to 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to end of treatment period at 6 months
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.	across all visits during treatment period (up to 6 months)
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.	baseline to end of treatment period at 6 months
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.	across all visits during treatment period (up to 6 months)
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.	baseline to end of treatment period at 6 months
Number of IAE Events Across All Treatment Visits		across all visits during treatment period (up to 6 months)
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.	baseline to end of treatment period at 6 months
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.	baseline, end of treatment period at 6 months, follow up at 9 months
Number of Participants Who Used Rescue Medication or Corticosteroids		baseline, end of treatment period at 6 months, follow up at 9 months
Number of Times Rescue Medications Were Used During the Treatment Period		up to 26 weeks

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Novartis Pharmaceuticals
• Investigators: Principal Investigator: Sameer Mathur, MD/PhD, UW Madison; Principal Investigator: Ravi Viswanathan, MD, UW Madison

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2017
• Primary Completion (Actual): January 6, 2020
• Study Completion (Actual): January 6, 2020

Study Registration Dates

• First Submitted: November 15, 2016
• First Submitted That Met QC Criteria: November 15, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Angioedema; Idiopathic Angioedema; IAE
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Angioedema; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Omalizumab
• Other Study ID Numbers: 2016-0645; SMPH/MEDICINE/MEDICINE*A (Other Identifier: UW Madison); A534220 (Other Identifier: UW Madison); Protocol Version 5/22/2018 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No