Ignite Creation Date:
2024-05-05 @ 9:27 PM
Last Modification Date:
2024-10-26 @ 10:04 AM
Study NCT ID:
NCT00890162
Status:
COMPLETED
Last Update Posted:
2019-07-01
First Post:
2009-04-28
Brief Title:
A Randomized Double-Blind Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Randomized Double-Blinded Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis
Status:
COMPLETED
Status Verified Date:
2018-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Omalizumab is an approved drug for the treatment of asthma by the Food and Drug Administration
Researchers are now studying this drug in a double-blind placebo-controlled manner to assess efficacy in patients with idiopathic anaphylaxis recurrent hypersensitive allergic episodes for which a cause is not identified
The study will improve understanding of the mechanisms involved in anaphylactic reactions as a response to the downregulation a decrease in the number of receptors on the surface of cells in mast cell a resident cell with several types of tissues activation and lead to the development of strategies to better prevent or treat anaphylaxis
Objectives
To determine whether treatment with omalizumab will reduce or prevent episodes of unprovoked anaphylaxis an acute allergic reaction in subjects with a history of idiopathic anaphylaxis
To assess pharmacodynamics physiological effects of a drug and identify patients with undiagnosed mastocytosis rare disorders caused by too many mast cells
To investigate cellular and molecular mechanisms of signaling and the effect of omalizumab on mast cells or basophils a cell in the leukocyte family that releases histamine which affects allergic response and explore other regulatory pathways that may be involved with modulation of mast cell degranulation
Eligibility
Patients between 18 and 70 years of age who have been diagnosed with idiopathic anaphylaxis a diagnosis that is made only after other causes of anaphylaxis have been considered
Patients with documented anaphylaxis episodes mild to severe at least six times within the past 1 year period at least once within the last 4 months and with at least one of the following
Elevated serum tryptase above baseline within 2 hours of the event
Emergency room visit with documented anaphylaxis without a known cause established by the acute onset of an illness minutes to several hours with involvement of the skin mucosal tissue or both generalized hives itching or flushing swollen lips-tongue-throat and at least one of the following 1 respiratory compromise or gastrointestinal involvement shortness of breath wheeze-bronchospasm throat tightness low oxygen levels nausea vomiting or abdominal pain or 2 reduced blood pressure or associated symptoms of end-organ dysfunction collapse loss of consciousness or loss of bladder or bowel control
Hospitalization for anaphylaxis
Patients must provide a letter of referral with copies of pertinent medical history and laboratory tests from the prospective participant s local physician and have the ability to give informed consent
Women with childbearing potential must have a negative pregnancy test and must agree to practice abstinence or effective birth control from the start of the protocol and for 3 months following the last injection of the study drug
Design
Participants will undergo a clinical evaluation blood tests and a bone marrow biopsy and aspirate
Participants will be randomized to either drug or placebo and will receive two doses of omalizumab or a matched placebo while hospitalized followed by continued outpatient therapy every 2 to 4 weeks for up to 6 months
Participants will remain on the assigned regimen for 6 months or until they have experienced new onset of severe adverse event on one occasion within 24 hours of study medication that are related to the study drug whichever comes first At that time the participant will be discontinued from drug administration
Omalizumab is an approved drug for the treatment of asthma by the Food and Drug Administration
Researchers are now studying this drug in a double-blind placebo-controlled manner to assess efficacy in patients with idiopathic anaphylaxis recurrent hypersensitive allergic episodes for which a cause is not identified
The study will improve understanding of the mechanisms involved in anaphylactic reactions as a response to the downregulation a decrease in the number of receptors on the surface of cells in mast cell a resident cell with several types of tissues activation and lead to the development of strategies to better prevent or treat anaphylaxis
Objectives
To determine whether treatment with omalizumab will reduce or prevent episodes of unprovoked anaphylaxis an acute allergic reaction in subjects with a history of idiopathic anaphylaxis
To assess pharmacodynamics physiological effects of a drug and identify patients with undiagnosed mastocytosis rare disorders caused by too many mast cells
To investigate cellular and molecular mechanisms of signaling and the effect of omalizumab on mast cells or basophils a cell in the leukocyte family that releases histamine which affects allergic response and explore other regulatory pathways that may be involved with modulation of mast cell degranulation
Eligibility
Patients between 18 and 70 years of age who have been diagnosed with idiopathic anaphylaxis a diagnosis that is made only after other causes of anaphylaxis have been considered
Patients with documented anaphylaxis episodes mild to severe at least six times within the past 1 year period at least once within the last 4 months and with at least one of the following
Elevated serum tryptase above baseline within 2 hours of the event
Emergency room visit with documented anaphylaxis without a known cause established by the acute onset of an illness minutes to several hours with involvement of the skin mucosal tissue or both generalized hives itching or flushing swollen lips-tongue-throat and at least one of the following 1 respiratory compromise or gastrointestinal involvement shortness of breath wheeze-bronchospasm throat tightness low oxygen levels nausea vomiting or abdominal pain or 2 reduced blood pressure or associated symptoms of end-organ dysfunction collapse loss of consciousness or loss of bladder or bowel control
Hospitalization for anaphylaxis
Patients must provide a letter of referral with copies of pertinent medical history and laboratory tests from the prospective participant s local physician and have the ability to give informed consent
Women with childbearing potential must have a negative pregnancy test and must agree to practice abstinence or effective birth control from the start of the protocol and for 3 months following the last injection of the study drug
Design
Participants will undergo a clinical evaluation blood tests and a bone marrow biopsy and aspirate
Participants will be randomized to either drug or placebo and will receive two doses of omalizumab or a matched placebo while hospitalized followed by continued outpatient therapy every 2 to 4 weeks for up to 6 months
Participants will remain on the assigned regimen for 6 months or until they have experienced new onset of severe adverse event on one occasion within 24 hours of study medication that are related to the study drug whichever comes first At that time the participant will be discontinued from drug administration
Detailed Description:
Anaphylaxis is a severe systemic reaction caused by release of mediators from mast cells and basophils Manifestations include cutaneous respiratory cardiovascular or gastrointestinal signs and symptoms Although anaphylaxis is frequently attributed to exposure to specific foods drugs and insect venoms in sensitive individuals a causative factor is not identified in 30 to 50 of patients with recurrent anaphylactic episodes idiopathic anaphylaxis
Currently therapeutic options for the treatment of idiopathic anaphylaxis are limited with variable efficacy This pilot study will examine the hypothesis that omalizumab Xolair will decrease episodes of unexplained anaphylaxis in patients with idiopathic anaphylaxis Omalizumab is approved for use in asthma We will examine the safety profile and efficacy of omalizumab in patients with anaphylaxis In addition the study will investigate whether patients with anaphylaxis have unique molecular and cellular defects in mast cells that result in these cells being more susceptible to degranulation
The study will enroll patients with idiopathic anaphylaxis Patients will undergo a clinical evaluation blood tests and a bone marrow biopsy and aspirate Patients will be randomized to either drug or placebo and will receive in a double-blind placebo-controlled approach 2 doses of omalizumab or a matched placebo while hospitalized followed by continued outpatient therapy every 2 to 4 weeks for up to 6 months Patients will remain on the assigned regimen if they have experienced anaphylactic events post 24-hr window determined to be unrelated to study drug or have been followed for 6 months whichever comes first These unrelated events would be determined by the PI not to jeopardize patient safety or restrict the use of additional therapy such as corticosteroids to control symptoms After this point the patient may be discontinued from drug administration until unblinding This design ensures that no patient will have anaphylactic episodes while on placebo if other therapy is medically indicated Research studies will be conducted to elucidate other markers or pathways of mast cell regulation
The primary outcome will be a reduction in the number and timing of anaphylactic events during the randomized phase Secondary outcomes will include a reduction in surface IgE receptors on basophils identification of mutations in c-kit and evaluation of the efficacy of omalizumab on other mediator-induced symptoms associated with anaphylaxis The study will improve the understanding of the mechanisms involved in anaphylactic reactions as a response to the downregulation of mechanisms involved in mast cell activation that could in turn lead to development of strategies to better prevent or treat anaphylaxis
Currently therapeutic options for the treatment of idiopathic anaphylaxis are limited with variable efficacy This pilot study will examine the hypothesis that omalizumab Xolair will decrease episodes of unexplained anaphylaxis in patients with idiopathic anaphylaxis Omalizumab is approved for use in asthma We will examine the safety profile and efficacy of omalizumab in patients with anaphylaxis In addition the study will investigate whether patients with anaphylaxis have unique molecular and cellular defects in mast cells that result in these cells being more susceptible to degranulation
The study will enroll patients with idiopathic anaphylaxis Patients will undergo a clinical evaluation blood tests and a bone marrow biopsy and aspirate Patients will be randomized to either drug or placebo and will receive in a double-blind placebo-controlled approach 2 doses of omalizumab or a matched placebo while hospitalized followed by continued outpatient therapy every 2 to 4 weeks for up to 6 months Patients will remain on the assigned regimen if they have experienced anaphylactic events post 24-hr window determined to be unrelated to study drug or have been followed for 6 months whichever comes first These unrelated events would be determined by the PI not to jeopardize patient safety or restrict the use of additional therapy such as corticosteroids to control symptoms After this point the patient may be discontinued from drug administration until unblinding This design ensures that no patient will have anaphylactic episodes while on placebo if other therapy is medically indicated Research studies will be conducted to elucidate other markers or pathways of mast cell regulation
The primary outcome will be a reduction in the number and timing of anaphylactic events during the randomized phase Secondary outcomes will include a reduction in surface IgE receptors on basophils identification of mutations in c-kit and evaluation of the efficacy of omalizumab on other mediator-induced symptoms associated with anaphylaxis The study will improve the understanding of the mechanisms involved in anaphylactic reactions as a response to the downregulation of mechanisms involved in mast cell activation that could in turn lead to development of strategies to better prevent or treat anaphylaxis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 09-I-0129 | None | None | None |