Clinical trial NCT02966314: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Idiopathic Angioedema
Keywords: Angioedema
Idiopathic Angioedema
IAE
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2016-11-17
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean 7-day Angioedema Activity Score (AAS7)
timeFrame: baseline to end of treatment period at 6 months
measure: Presence of a 7-day Angioedema Activity Score (AAS7) Greater Than 0 Across All Treatment Visits
timeFrame: across all visits during treatment period (up to 6 months)
Secondary outcomes:
measure: Mean Angioedema Quality of Life (AE-QoL) Questionnaire
timeFrame: baseline to end of treatment period at 6 months
measure: Mean Angioedema Quality of Life (AE-QoL) Questionnaire Across All Treatment Visits
timeFrame: across all visits during treatment period (up to 6 months)
measure: Mean Visual Analog Scale
timeFrame: baseline to end of treatment period at 6 months
measure: Presence of Visual Analog Scale Less Than 100 Across All Treatment Visits
timeFrame: across all visits during treatment period (up to 6 months)
measure: Mean Number of IAE Episodes 2 Weeks Prior to Randomization
timeFrame: baseline to end of treatment period at 6 months
measure: Number of IAE Events Across All Treatment Visits
timeFrame: across all visits during treatment period (up to 6 months)
measure: Change in Duration of IAE Episodes
timeFrame: baseline to end of treatment period at 6 months
measure: Number of Participants Who Visited Urgent Care or Emergency Room
timeFrame: baseline, end of treatment period at 6 months, follow up at 9 months
measure: Number of Participants Who Used Rescue Medication or Corticosteroids
timeFrame: baseline, end of treatment period at 6 months, follow up at 9 months
measure: Number of Times Rescue Medications Were Used During the Treatment Period
timeFrame: up to 26 weeks
Other outcomes:
Locations:
city: Madison
country: United States
facility: UW Madison
state: Wisconsin
Study officials:
affiliation: UW Madison
name: Sameer Mathur, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UW Madison
name: Ravi Viswanathan, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.