Clinical trial NCT00318747: Treatment of Ragweed-Allergic Asthma With an Immunostimulatory Drug
Official title: Asthma Immunotherapy With a Ragweed Allergen Immunostimulatory Sequence Conjugate
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Allergy
Allergic Rhinitis
Rhinitis, Allergic, Seasonal
Keywords: Amb a 1-Immunostimulatory Oligodeoxyribonucleotide Conjugate
AIC
Amb a I Protein
Ragweed Allergy
Hay Fever
Wheeze
Immunotherapy
Tolerance
Immunostimulatory
Ragweed Season
Asthma
Asthmatics
Asthmatic
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2006-04-27
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will test the effectiveness of an investigational treatment for patients with ragweed-induced asthma, sometimes called fall seasonal asthma. The treatment being tested is a series of anti-ragweed shots. The purpose of the study is to determine whether a short series of injections with Amb a 1-immunostimulatory oligodeoxyribonucleotide conjugate (AIC) can cause a long-lasting reduction in the symptoms of asthma that are caused by fall hay fever allergies.

Detailed description: Ragweed allergy is a common trigger of asthmatic flare-ups in people with asthma. Individuals with ragweed allergy suffer increased asthma symptoms during the fall allergy season, which generally runs from August to November. These flare-ups can significantly impact an asthma patient's quality of life. AIC is an investigational medicine that combines special DNA sequences that can modify the way the immune system responds. In AIC, these sequences are linked to a piece of the ragweed pollen molecule (known as Amb a 1) that causes hay fever symptoms. Injections of AIC have been shown to change the way the immune system responds to ragweed pollen in both animals and humans in a way that may lead to reduced hay fever symptoms.

In a previous study, AIC was safe and well tolerated, and patients exhibited a decrease in allergy symptoms lasting up to 2 years after treatment on average. This study will evaluate whether short-term use of AIC during the spring can cause long-term immune tolerance to ragweed, reduce asthma symptoms, and decrease use of asthma medications for future allergy seasons.

During the 2007 fall ragweed allergy season, participants will be observed and be asked to keep a diary of their asthma symptoms and medication use. In the spring of 2008, participants will be randomly assigned to receive six weekly doses of either the experimental medicine or placebo. Participants will be observed again for the 2008 fall ragweed season. Another series of three weekly doses of the assigned study treatment will be given in spring 2009, with observation through the 2009 fall ragweed allergy season and possibly the 2010 season. During the observation periods, participants will be asked to track their asthma symptoms and medication use and report this information to study staff. Study visits will be weekly during the spring and biweekly during the ragweed season, with a maximum of 16 visits per year. Allergy and lung tests as well as blood and urine collection will occur at selected study visits; these tests are designed to measure the participants' immune response.

Eligibility criteria: Inclusion Criteria:

* History of asthma
* History of asthma medication use during the 2005 fall ragweed season
* Suspected ragweed allergy
* Positive laboratory tests for ragweed allergy

Exclusion Criteria:

* Received immunotherapy for ragweed or other allergens within the 5 years prior to study entry
* Received anti-IgE (omalizumab) within the year prior to study entry
* 3 or more courses of oral corticosteroids for asthma within the year prior to study entry
* Inpatient hospitalization for asthma within the 5 years prior to study entry
* History of respiratory failure or intubation for asthma
* Smoking within the 6 months prior to study entry
* Greater than 5 pack/year history of smoking
* Clinically significant acute or chronic illness
* Chronic immunodeficiency

Primary outcomes:
measure: Change in average daily asthma medication use between the 2007 and 2008 ragweed seasons
Secondary outcomes:
measure: Effect of AIC on selected secondary clinical outcome measures
measure: safety of AIC in this population
measure: mechanisms through which AIC may induce tolerance to ragweed
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
Study officials:
affiliation: University of California, San Diego
name: David Broide, MD
role: STUDY_CHAIR
affiliation: Johns Hopkins University
name: Peter Creticos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simons FE, Shikishima Y, Van Nest G, Eiden JJ, HayGlass KT. Selective immune redirection in humans with ragweed allergy by injecting Amb a 1 linked to immunostimulatory DNA. J Allergy Clin Immunol. 2004 Jun;113(6):1144-51. doi: 10.1016/j.jaci.2004.03.003.
citation: Tulic MK, Fiset PO, Christodoulopoulos P, Vaillancourt P, Desrosiers M, Lavigne F, Eiden J, Hamid Q. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J Allergy Clin Immunol. 2004 Feb;113(2):235-41. doi: 10.1016/j.jaci.2003.11.001.