Omalizumab (Xolair) and Allergy Shots For the Treatment of Seasonal Allergies

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00078195
First received: February 19, 2004
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

A series of allergy shots may reduce symptoms of seasonal ragweed allergies. This study will determine whether taking a drug called omalizumab (also known as Xolair) before getting the allergy shots is more effective than allergy shots alone or other treatments, such as prescription antihistamines.


Condition Intervention Phase
Hay Fever
Hypersensitivity
Allergy
Rhinitis
Biological: omalizumab
Biological: Placebo omalizumab
Biological: Ragweed rush immunotherapy (RIT)
Biological: Placebo rush immunotherapy (RIT)
Biological: Ragweed immunotherapy (IT)
Biological: Placebo immunotherapy (IT)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Efficacy and Safety Evaluation of Allergen Immunotherapy Co-Administered With Omalizumab, an Anti-IgE Monoclonal Antibody (ITN019AD)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Average daily allergy severity score [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: No ]
    The average daily allergy severity score will be calculated from participants' 5 symptom scores (sneezing; rhinorrhea/runny nose; itchy nose, throat, and palate; itchy, watery eyes; and nasal congestion/stuffiness) during the ragweed pollen season. Symptom scores are recorded twice daily (AM and PM). The sum of the individual symptom scores will be averaged over AM and PM to give a daily score. Each daily score will then be averaged to obtain one measure of the average daily allergy severity score for each participant. The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.


Secondary Outcome Measures:
  • Incidence and severity of adverse events [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: Yes ]
    The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.

  • Number of days with rescue medication (fexofenadine HCl 60 mg) use [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: No ]
    The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.

  • Number of rescue medication capsules used [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: No ]
    The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.

  • Rhinoconjunctivitis quality of life (QOL) questionnaire (RQLQ) scores [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: No ]
    The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.

  • Daily morning allergy symptom scores [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: No ]
    The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.

  • Daily nighttime allergy symptom scores during the 2003 ragweed season [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: No ]
    The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.

  • Individual allergy symptom scores during the 2003 ragweed season [ Time Frame: 2003 ragweed pollen season ] [ Designated as safety issue: No ]
    The ragweed pollen season begins when the ragweed pollen counts rise to 10 ragweed pollen grains/m3/24 hours or above on two consecutive recorded days, and the ragweed pollen season ends when the ragweed pollen counts fall below 10 ragweed pollen grains/m3/24 hours on two consecutive recorded days. The ragweed pollen season is from approximately August 15, 2003 to October 1, 2003, but varies among the sites.


Estimated Enrollment: 168
Study Start Date: April 2003
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omalizumab pre-treatment, ragweed RIT, omalizumab + ragweed IT
Participants are pre-treated with omalizumab followed by ragweed rush immunotherapy (RIT) followed by dual therapy with omalizumab plus ragweed immunotherapy (IT).
Biological: omalizumab
A minimum equivalent dose of 0.016 mg/kg/IgE (IU/mL) every 4 weeks will be administered. Omalizumab is administered in two separate phases. In the pre-treatment period omalizumab will be administered to condition the participants to an immune tolerance state. Omalizumab will be also administered after RIT and during the maintenance immunotherapy phase.
Other Names:
  • Xolair™
  • anti-Immunoglobulin E (IgE)
Biological: Ragweed rush immunotherapy (RIT)
RIT will consist of a series of injections containing ragweed extract. The series of injections will have progressively greater amounts of ragweed extract: starting from the 1:1000 dilution of the maintenance vial and progressing to the 0.3 mL of 1:10 dilution of the maintenance vial or the maximally tolerated amount.
Biological: Ragweed immunotherapy (IT)
Participants will receive weekly maintenance IT dosing for a total of 12 weeks.
Experimental: Omalizumab pre-treatment, omalizumab
Participants are pre-treated with omalizumab followed by placebo rush immunotherapy (RIT), followed by dual therapy with Omalizumab plus placebo immunotherapy (IT).
Biological: omalizumab
A minimum equivalent dose of 0.016 mg/kg/IgE (IU/mL) every 4 weeks will be administered. Omalizumab is administered in two separate phases. In the pre-treatment period omalizumab will be administered to condition the participants to an immune tolerance state. Omalizumab will be also administered after RIT and during the maintenance immunotherapy phase.
Other Names:
  • Xolair™
  • anti-Immunoglobulin E (IgE)
Biological: Placebo rush immunotherapy (RIT)
The placebo for rush immunotherapy will contain the diluents and histamine.
Biological: Placebo immunotherapy (IT)
The placebo for immunotherapy will contain the diluents and histamine.
Active Comparator: Ragweed RIT, ragweed IT
Participants are pre-treated with placebo omalizumab followed by ragweed rush immunotherapy (RIT), followed by dual therapy with placebo omalizumab plus ragweed immunotherapy (IT).
Biological: Placebo omalizumab
The placebo for omalizumab will contain the excipients and diluents of the omalizumab.
Biological: Ragweed rush immunotherapy (RIT)
RIT will consist of a series of injections containing ragweed extract. The series of injections will have progressively greater amounts of ragweed extract: starting from the 1:1000 dilution of the maintenance vial and progressing to the 0.3 mL of 1:10 dilution of the maintenance vial or the maximally tolerated amount.
Biological: Ragweed immunotherapy (IT)
Participants will receive weekly maintenance IT dosing for a total of 12 weeks.
Placebo Comparator: Placebo
Participants are pre-treated with placebo omalizumab followed by placebo rush immunotherapy (RIT), followed by dual therapy with placebo omalizumab plus placebo immunotherapy (IT).
Biological: Placebo omalizumab
The placebo for omalizumab will contain the excipients and diluents of the omalizumab.
Biological: Placebo rush immunotherapy (RIT)
The placebo for rush immunotherapy will contain the diluents and histamine.
Biological: Placebo immunotherapy (IT)
The placebo for immunotherapy will contain the diluents and histamine.

Detailed Description:

Allergic rhinitis affects 20 to 40 million Americans annually. Allergy symptoms, which can range from mild to seriously debilitating, may affect quality of life. Left untreated, allergic rhinitis can exacerbate or trigger more serious conditions, such as asthma and sinus inflammation.

Individuals with allergies react to harmless particles such as dust or pollen. Proteins in the blood called IgE antibodies treat the harmless particles as invaders and trigger an immune system response. The immune response results in harmful inflammation of healthy tissues. In ragweed allergy, inflammation occurs in the airways and causes familiar allergy symptoms like sneezing, coughing, and general discomfort.

Omalizumab is an investigational drug that has been shown to block the effects of IgE antibodies. The blocking effect of omalizumab is temporary, but giving the drug to people before their regular allergy shots may make the shots more effective.

Participants in this study will be randomly assigned to receive injections of omalizumab or a placebo before an accelerated course of allergy shots (given over 12 weeks). The participants will return for follow-up for up to one year, and they may have as many as 27 study visits.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Able to comprehend and grant a witnessed, written informed consent prior to any study procedures.
  • Female participants of child bearing age must have a negative urine pregnancy test at Screening Visit and subsequent visits. In addition, female participants must be using a medically acceptable form of birth control.
  • History of seasonal allergic rhinitis for at least 2 years with symptoms during the ragweed pollen season requiring pharmacotherapy.
  • A positive skin test by prick method to ragweed pollen at the Screening Visit. A positive skin prick test will be defined as a ragweed pollen-induced wheal greater than 3 mm larger in diameter than diluent control (measurements will be made 15-20 minutes after application).
  • Must be capable of faithfully completing the diary and of attending regularly scheduled study visits.
  • Must intend to remain in the ragweed pollen area during the entire ragweed season.
  • Willing to avoid prohibited medications for the periods indicated in the protocol.
  • Participants must meet pretrial eligibility requirements for trial enrollment (acceptable medical history, physical examination results, normal electrocardiogram and acceptable laboratory test results).
  • Participants must have a baseline serum Immunoglobulin E (IgE) level greater than 10 and less than 700 IU/mL.

Exclusion Criteria

  • weigh less than 30 kg or more than 120 kg.
  • pregnant or lactating.
  • history of severe anaphylactoid (non-IgE mediated) or anaphylactic reactions).
  • history of immunotherapy within the past 10 years, if received one full year of immunotherapy, or within the past 5 years if received less than one year of immunotherapy.
  • known hypersensitivity to trial rescue medication (fexofenadine HCl).
  • taking beta-adrenergic antagonists in any form.
  • taking allergic ophthalmologic medication.
  • clinically significant perennial rhinitis that would interfere in assessment of ragweed-induced seasonal allergic rhinitis symptoms.
  • Presence of a severely deviated nasal septum, septal perforation, structural nasal defect or large nasal polyps causing obstruction.
  • History of an upper respiratory or sinus infection requiring treatment with an antibiotic within 2 weeks prior to Screening Visit.
  • Documented evidence of acute or significant chronic sinusitis, as determined by the Investigator.
  • Asthma (either history of, abnormal spirometry, [forced expiratory volume in 1 second (FEV1) less than 80% predicted] or use of asthma medications).
  • Chronic or intermittent use of inhaled, oral, intra-muscular, or intra-venous corticosteroids; or chronic or intermittent use of topical corticosteroids within 4 weeks of Visit Screening Visit.
  • Chronic use of medications (e.g., tricyclic antidepressants) that would affect assessment of the effectiveness of the study medication.
  • Rhinitis medicamentosa.
  • History or presence of significant renal, hepatic, neurologic, cardiovascular, hematologic, metabolic, cerebrovascular, respiratory, gastrointestinal or other significant medical condition including, autoimmune or collagen vascular disorders, aside from organ-specific autoimmune disease limited to the thyroid that in the Investigator's opinion could interfere with the study or require medical treatment that would interfere with the study.
  • History of cancer other than basal cell carcinoma of the skin.
  • History within the past year of excessive alcohol intake or drug addiction.
  • Current smokers, greater than 10 pack year history, or participants who quit smoking less than one year prior to Screening.
  • Use of any prohibited concomitant medications during the washout period (i.e., before screening) and throughout the study period.
  • Participants currently undergoing immunotherapy.
  • Participants with clinically significant abnormality on 12-lead Electrocardiogram (ECG) on screening visit.
  • Treatment with an experimental, non-approved drug, or investigational drug within the past 30 days.
  • Participants with a history of noncompliance to medical regimens and participants who are considered potentially unreliable.
  • Previous treatment with a monoclonal antibody for any reason including anti-IgE in any form (e.g., omalizumab).
  • Participants with known hypersensitivity to trial drug ingredients (i.e., sucrose, histidine, polysorbate 20) or related drugs (i.e., monoclonal antibody; polyclonal gamma-globulin).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00078195

Locations
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Nebraska
Creighton University
Omaha, Nebraska, United States, 68131
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: Thomas Casale, MD Creighton University
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00078195     History of Changes
Other Study ID Numbers: DAIT ITN019AD
Study First Received: February 19, 2004
Last Updated: June 4, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Ragweed
Immunotherapy
Rush Immunotherapy
RIT
Hayfever
Seasonal Allergic Rhinitis

Additional relevant MeSH terms:
Rhinitis
Hypersensitivity
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Immune System Diseases
Omalizumab
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on September 30, 2014