Idiopathic AngioedemaPhase 4NCT02966314

Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy

A Phase 4 study testing Omalizumab in people with Idiopathic Angioedema, run by University of Wisconsin, Madison at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Idiopathic Angioedema
What is being tested?: Omalizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 30 Mar 2017to 6 Jan 2020
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

UW Madison
Madison, Wisconsin, 53792

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Idiopathic Angioedema
Being tested: Omalizumab, Placebos
Keywords: Angioedema, Idiopathic Angioedema, IAE
Medical subject headings: Angioedema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OmalizumabDrug
Also called Xolair
Omalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.
PlacebosDrug
Placebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.

Study groups in NCT02966314
Study group	Role	What they receive
Placebo	Placebo comparator	Placebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection. Receives: Drug: Placebos
Omalizumab	Active comparator	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. Receives: Drug: Omalizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: across all visits during treatment period (up to 6 months)

Secondary outcomes (10)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: baseline to end of treatment period at 6 months
Number of IAE Events Across All Treatment Visits
Measured: 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.
Measured: 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.
Measured: baseline, end of treatment period at 6 months, follow up at 9 months
Number of Participants Who Used Rescue Medication or Corticosteroids
Measured: baseline, end of treatment period at 6 months, follow up at 9 months
Number of Times Rescue Medications Were Used During the Treatment Period
Measured: up to 26 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Mar 20176 Jan 2020

First posted17 Nov 2016 (estimated)
Study start30 Mar 2017
Primary completion6 Jan 2020
Study completion6 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Idiopathic AngioedemaStudies of the same condition, open and under way.
More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02966314
Sponsor's protocol ID: 2016-0645
Other IDs: SMPH/MEDICINE/MEDICINE*A, A534220, Protocol Version 5/22/2018
Status last verified: Oct 2022
First submitted: 15 Nov 2016
Last updated: 1 Nov 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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.
PubMed 35914662

Study at a glance

From the registry record, last updated by the sponsor on 1 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02966314
Acronym / sponsor ID: 2016-0645
Conditions: Idiopathic Angioedema
Keywords: Angioedema, Idiopathic Angioedema, IAE
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: University of Wisconsin, MadisonUniversity, hospital or other
Collaborators: Novartis Pharmaceuticals
Study start: 30 Mar 2017 (actual)
Primary completion: 6 Jan 2020 (actual)
Study completion: 6 Jan 2020 (actual)
First posted: 17 Nov 2016 (estimated)
Results: Posted 22 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, care provider)
Number of arms: 2

Arm	Type	Receives
Placebo	Placebo comparator	Drug: PlacebosPlacebo contains sodium chloride 0.9% and will be provided by Novartis. Placebo will be administered as a subcutaneous injection.
Omalizumab	Active comparator	Drug: OmalizumabOmalizumab 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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)

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OmalizumabAlso: XolairOmalizumab 300mg subcutaneous injection once monthly for 6 months. Total dose will be divided into two 150mg/1.2mL injections.	Drug	Omalizumab
PlacebosPlacebo Group (Sodium Chloride 0.9%) two 1.2mL subcutaneous injections once monthly for 6 months.	Drug	Placebo

Primary outcome

Mean 7-day Angioedema Activity Score (AAS7)
Time frame: baseline to end of treatment period at 6 months
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
Time frame: across all visits during treatment period (up to 6 months)
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.

10 secondary outcomes

Mean Angioedema Quality of Life (AE-QoL) Questionnaire
Time frame: baseline to end of treatment period at 6 months
Mean Angioedema Quality of Life (AE-QoL) Questionnaire Across All Treatment Visits
Time frame: across all visits during treatment period (up to 6 months)
Mean Visual Analog Scale
Time frame: baseline to end of treatment period at 6 months
Presence of Visual Analog Scale Less Than 100 Across All Treatment Visits
Time frame: across all visits during treatment period (up to 6 months)
Mean Number of IAE Episodes 2 Weeks Prior to Randomization
Time frame: baseline to end of treatment period at 6 months
Number of IAE Events Across All Treatment Visits
Time frame: across all visits during treatment period (up to 6 months)
Change in Duration of IAE Episodes
Time frame: baseline to end of treatment period at 6 months
Number of Participants Who Visited Urgent Care or Emergency Room
Time frame: baseline, end of treatment period at 6 months, follow up at 9 months
Number of Participants Who Used Rescue Medication or Corticosteroids
Time frame: baseline, end of treatment period at 6 months, follow up at 9 months
Number of Times Rescue Medications Were Used During the Treatment Period
Time frame: up to 26 weeks

Results and safety

Results posted to the registry on 22 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	5	4
Omalizumab	5	5

Primary outcome: Mean 7-day Angioedema Activity Score (AAS7)

Time frame: baseline to end of treatment period at 6 months. Mean (Full Range). Unit: score on a scale

Measure	Placebo n = 5	Omalizumab n = 5
baseline (2 weeks prior to randomization)	2.8 (0 to 9)	1.6 (0 to 4)
6 months	0.69 (0 to 1.75)	0.20 (0 to 1)

Primary outcome: Presence of a 7-day Angioedema Activity Score (AAS7) Greater Than 0 Across All Treatment Visits

Time frame: across all visits during treatment period (up to 6 months). Count of units. Unit: participant visits

Measure	Placebo n = 5	Omalizumab n = 5
Value	38	4

Placebo vs Omalizumab: Odds Ratio (OR): 18.7 (95% CI 2.77 to 126.47), p = 0.003, Regression, Logistic

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: up to 9 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	0 of 5 (0%)	0 of 5 (0%)	0 of 5
Omalizumab	0 of 5 (0%)	1 of 5 (20%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 35914662Goswamy 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.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sameer Mathur, MD/PhD principal investigator

UW Madison

Ravi Viswanathan, MD principal investigator

UW Madison

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Omalizumab in people with Idiopathic Angioedema, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean 7-day Angioedema Activity Score (AAS7) (time frame: baseline to end of treatment period at 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02966314, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2022.