A Randomized, Double-Blind, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis

NCT00890162 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 09012909-I-0129
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Anaphylaxis; Hypotension; Bronchospasm; Angioedema

Keywords

Omalizumab; Idiopathic Anaphylaxis; Serum Tryptase; Placebo-Controlled; Adult; Anaphylaxis; Allergic Reaction

Outcome Measures

Primary Outcomes (1)

• Reduction in the Number and Timing of Anaphylactic Events in Subjects With a History of Frequent Idiopathic Anaphylaxis.

  To determine if treatment with omalizumab over 6 months will produce a reduction in the number and timing of anaphylactic events in subjects with a history of frequent idiopathic anaphylaxis. Ordinal outcome of participants based on number of events in 6 months after baseline and timing of first event. Events were calculated based on detailed event logs maintained by the patients and collected every 2-4 weeks based on injection schedule. Mean percent change in number of events experienced while on study agent for each subject and results presented as a group.

  6 months

Study Arms (2)

Omalizumab

ACTIVE COMPARATOR

Subjects will receive two doses of Omalizumab while hospitalized, followed by continued outpatient therapy, every 2 to 4 weeks, for up to 6 months.

Drug: Epinephrine; Drug: Omalizumab (Xolair)

Placebo

PLACEBO COMPARATOR

Subjects will receive two doses of placebo while hospitalized, followed by continued outpatient therapy, every 2 to 4 weeks, for up to 6 months.

Drug: Epinephrine; Drug: Placebos

Interventions

Epinephrine DRUG

Omalizumab; Placebo

Omalizumab (Xolair) DRUG

Omalizumab

Placebos DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be at least 18 years of age and no older than 70 years of age.
• Anaphylaxis episodes (mild-severe) at least 6 times within the past 1 year period, documented according to medical records physician report, or patient report and 1 episode within the last 4 months, and with at least 1 of the following:
• Elevated serum tryptase above baseline within 2 hours of the event.
• Emergency room visit with documented anaphylaxis without an etiology established by the acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) \[Grade 1\]\* and at least 1 of the following:
• Respiratory compromise or gastrointestinal involvement (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia, nausea, vomiting, or abdominal pain \[Grade 2\]\*).
• Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia \[collapse\], syncope, or incontinence \[Grade 3\]\*).
• Hospitalization for anaphylaxis: hospital records with documented anaphylaxis without known cause established by the acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) \[Grade 1\]\*) and at least one of the following:
• Respiratory compromise or gastrointestinal involvement (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia, nausea, vomiting, or abdominal pain \[Grade 2\]\*).
• Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia \[collapse\], syncope, or incontinence \[Grade 3\]\*).
• Letter of referral, with copies of pertinent medical history and laboratory tests, from prospective study participant s local physician.
• Ability to give informed consent.
• Women of childbearing potential must have a negative beta-HCG serum or urine pregnancy test prior to each injection, and must agree to practice abstinence or effective contraception from initiation of the protocol and for 3 months following the last infusion of the study agent (effective contraception methods include abstinence; surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap, or sponge; or hormonal contraception).
• Severity grading of anaphylaxis

You may not qualify if:

• Presence of conditions which, in the judgment of the investigator or the referring physician, may put the subject at undue risk for study participation or travel (such as an acute infection, severe thrombocytopenia, coronary artery disease, uncontrolled hypertension, congestive heart failure, chronic beta blocker therapy such as atenolol or metoprolol, or myeloproliferative disease).
• History of malignancy
• Known cause for anaphylaxis or flushing
• Diagnosis of mastocytosis
• Inability to provide informed consent
• Inability or refusal to undergo a bone marrow biopsy and aspirate
• HIV positive or other known immunodeficiency
• Active or chronic hepatitis
• Use of any other investigational agent within 30 days of the study
• Current use of chronic-oral corticosteroids or other immunosuppressant medications
• Pregnant or nursing women
• Positive pregnancy test
• IgE levels and subject s weight that cause dosing to be above dosing guidelines.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Thong BY, Cheng YK, Leong KP, Tang CY, Chng HH. Anaphylaxis in adults referred to a clinical immunology/allergy centre in Singapore. Singapore Med J. 2005 Oct;46(10):529-34.

  PMID: 16172772 BACKGROUND

• Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol. 2006 Jul;97(1):39-43. doi: 10.1016/S1081-1206(10)61367-1.

  PMID: 16892779 BACKGROUND

• Neugut AI, Ghatak AT, Miller RL. Anaphylaxis in the United States: an investigation into its epidemiology. Arch Intern Med. 2001 Jan 8;161(1):15-21. doi: 10.1001/archinte.161.1.15.

  PMID: 11146694 BACKGROUND

• Carter MC, Robyn JA, Bressler PB, Walker JC, Shapiro GG, Metcalfe DD. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol. 2007 Jun;119(6):1550-1. doi: 10.1016/j.jaci.2007.03.032. Epub 2007 May 3. No abstract available.

  PMID: 17481708 BACKGROUND

• Constantine GM, Bressler PB, Petroni D, Metcalfe DD, Carter MC. Twelve-year follow-up of omalizumab therapy for anaphylaxis in 2 patients with systemic mastocytosis. J Allergy Clin Immunol Pract. 2019 Apr;7(4):1314-1316. doi: 10.1016/j.jaip.2018.07.041. Epub 2018 Aug 24. No abstract available.

  PMID: 30149096 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anaphylaxis; Hypotension; Bronchial Spasm; Angioedema; Hypersensitivity

Interventions

Epinephrine; Omalizumab

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Immune System Diseases; Vascular Diseases; Cardiovascular Diseases; Bronchial Diseases; Respiratory Tract Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Limitations and Caveats

Although we received multiple inquiries for this study, it was difficult to find subjects who met all eligibility criteria and who were also willing to participate in a double-blind placebo-controlled trial.

Results Point of Contact

• Title: Carter, Melody
• Organization: National Institute of Allergy and Infectious Diseases

mc396j@nih.gov

+1 301 496 8772

Study Officials

• Melody C Carter, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2009
• First Posted: April 29, 2009
• Study Start: April 27, 2009
• Primary Completion: July 31, 2018
• Study Completion: May 31, 2019
• Last Updated: July 1, 2019
• Results First Posted: July 1, 2019

Record last verified: 2018-08

Locations

US (1)