An Evaluation of the Efficacy and Safety of TOLAMBA™ for Ragweed-Allergic Rhinitis in an Environmental Exposure Chamber - Full Text View

Sponsor:	Dynavax Technologies Corporation
Information provided by:	Dynavax Technologies Corporation
ClinicalTrials.gov Identifier:	NCT00537355

Purpose

This will be a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. After passing the initial Screening Visit, subjects will be in the environmental exposure chamber(EEC), a room with a controlled amount of ragweed pollen, for 4 hours each day on 4 consecutive days. At the last visit, subjects who have achieved a minimum Total Nasal Symptom Score (TNSS) will be randomized to receive either TOLAMBA or placebo treatments. Subjects will receive 6 weekly subcutaneous (under the skin) injections of the study drug. About three weeks after the last injection, subjects will be asked to be in the EEC for 2 consecutive days (Visits 11 and 12, Days 60 and 61). Approximately 3 weeks after Visit 12 (Day 61), the subjects will again be in the EEC for 4 consecutive days (Visits 13-16, Days 82-85).

During all EEC visits, the subjects will be exposed to ragweed pollen at an average concentration of 3500 ± 500 pollen grains per cubic meter. Each EEC visit will last 4 hours. During each EEC visit, patients will be asked to record symptom scores for nasal and non-nasal symptoms at scheduled time points.

The total duration of a subject's participation in this study is expected to be a minimum of 85 days.

Condition	Intervention	Phase
Rhinitis, Allergic, Seasonal	Biological: Amb a 1 Immunostimulatory Oligoribonucleotide Conjugate Drug: Histamine	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of TOLAMBA™ in the Control of Symptoms of Ragweed-Allergic Rhinitis in an Environmental Exposure Chamber (EEC) Model

Resource links provided by NLM:

MedlinePlus related topics: Allergy Hay Fever

Drug Information available for: Histamine Histamine phosphate Histamine dihydrochloride

U.S. FDA Resources

Further study details as provided by Dynavax Technologies Corporation:

Primary Outcome Measures:

Total Nasal Symptom Score (TNSS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Total Non-Nasal Symptom Score (TNNSS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Total Symptom Score (TSS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
quality of life questionnaire [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment:	271
Study Start Date:	September 2007
Study Completion Date:	May 2008
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: TOLAMBA™	Biological: Amb a 1 Immunostimulatory Oligoribonucleotide Conjugate 6 weekly subcutaneous injections (escalating doses of 3 mcg to 30 mcg) Other Name: TOLAMBA™
Sham Comparator: Histamine Histamine simulates mild redness/swelling effect seen with active comparator, TOLAMBA™. Prevents study staff from easily identifying subjects who received active comparator.	Drug: Histamine 6 weekly subcutaneous injections (escalating doses of 0.22 mcg to 1.1 mcg) Other Name: Histatrol

Detailed Description:

Ragweed allergy is the most common seasonal allergy in North America. Allergen immunotherapy is a therapeutic option for patients who have allergy symptoms that cannot be adequately controlled by avoidance of the allergen or medication. It may also be appropriate for those who cannot tolerate their medications due to side effects or have difficulties with medication compliance.

This will be a randomized, double-blind, placebo-controlled, parallel-group, multicenter study. After passing the initial Screening Visit, subjects will be in the environmental exposure chamber(EEC), a room with a controlled amount of ragweed pollen, for 4 hours each day on 4 consecutive days. At the last visit, subjects who have achieved a minimum Total Nasal Symptom Score (TNSS) will be randomized to receive either TOLAMBA or placebo treatments. Subjects will receive 6 weekly subcutaneous (under the skin) injections of the study drug. About three weeks after the last injection, subjects will be asked to be in the EEC for 2 consecutive days (Visits 11 and 12, Days 60 and 61). Approximately 3 weeks after Visit 12 (Day 61), the subjects will again be in the EEC for 4 consecutive days (Visits 13-16, Days 82-85).

During all EEC visits, the subjects will be exposed to ragweed pollen at an average concentration of 3500 ± 500 pollen grains per cubic meter. Each EEC visit will last 4 hours. During each EEC visit, patients will be asked to record symptom scores for nasal and non-nasal symptoms at scheduled time points.

The total duration of a subject's participation in this study is expected to be a minimum of 85 days.

Comparison: Allergy symptoms of subjects treated with TOLAMBA™ compared with subjects treated with placebo.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Is willing and able to give signed informed consent, and must have provided this consent.
Has a clinical history of seasonal allergic rhinitis with seasonal nasal allergy symptoms during each of the last 2 ragweed allergy seasons.
Has documentation of a positive skin test to ragweed allergen within 12 months of screening.
Has minimum qualifying symptom scores at the last visit of the Pre-Treatment EEC sessions (Visit 5, Day 4).
If female of childbearing potential, is not pregnant and is consistently using an acceptable birth control method.
Is normally active and otherwise judged to be in good health on the basis of medical history, physical examination and routine laboratory tests.

Exclusion Criteria:

A woman who is pregnant, breastfeeding, or planning a pregnancy.
Has a history of more than mild asthma that requires the use of a daily inhaled or oral corticosteroid, leukotriene inhibitor, or cromolyn; or a daily inhaled short or long acting β-agonist.
Has had any hospital admissions for asthma, a recent (within the past 12 months)asthma exacerbation that required either oral or inhaled corticosteroids, or a prior history of unstable asthma.
Has received immunotherapy within the last 2 years that has contained ragweed pollen extract.
Has previously participated in a clinical trial with TOLAMBA or another ragweed-based immunotherapy.
Has received immunotherapy for any allergens within 30 days prior to Visit 1.
Has the need for use of antihistamines or corticosteroids on a regular basis (systemic or topical).
Has received anti-IgE antibody (Xolair®) within the past 12 months.
Is currently taking monoamine oxidase (MAO) inhibitors.
Has taken any systemic corticosteroids, immunomodulators, or immune suppressive medications within 4 weeks prior to Visit 1.
Has taken any antihistamine within 7 days prior to Visit 1 skin testing.
Requires use of β-adrenergic blockers or other agents that may interfere with the use of adrenaline.
Known current alcohol or drug abuse.
Current participation in another clinical study involving an investigational drug or device, or participation in such a study within 30 days prior to Visit 1.
Has a history of generalized anaphylaxis requiring medical attention.
Has moderate or severe allergy symptoms at Visit 1.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00537355

Locations

Canada, Ontario
Allied Research International Inc.
Mississauga, Ontario, Canada, L4W 1N2
Alpha Medical Research Inc.
Mississauga, Ontario, Canada, L5A 3V4
Allergy & Asthma Research Centre
Ottawa, Ontario, Canada, K1Y 4G2
Canada, Quebec
Anapharm
Montreal, Quebec, Canada, H3X 2H9
Division of Clinical Immunology and Allergy, The McGill University Health Centre
Montreal, Quebec, Canada, H3G 1A4
Canada
Centre De Recherche Appliquée en Allergie De Québec
Quebec, Canada, GIV 4M6

Sponsors and Collaborators

Dynavax Technologies Corporation

Investigators

Study Director:

Eduardo Martins, MD, DPhil

Dynavax Technologies Corporation

More Information

Additional Information:

sponsor website This link exits the ClinicalTrials.gov site

No publications provided by Dynavax Technologies Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Campbell JD, Buchmann P, Kesting S, Cunningham CR, Coffman RL, Hessel EM. Allergen-specific T cell responses to immunotherapy monitored by CD154 and intracellular cytokine expression. Clin Exp Allergy. 2010 Jul;40(7):1025-35. Epub 2010 Apr 13.

Responsible Party:	Eduardo Martins, MD, DPhil / Vice President, Clinical Development, Dynavax Technologies Corporation
ClinicalTrials.gov Identifier:	NCT00537355 History of Changes
Other Study ID Numbers:	DV1-SAR-11
Study First Received:	September 27, 2007
Last Updated:	September 8, 2010
Health Authority:	Canada: Health Canada

Keywords provided by Dynavax Technologies Corporation:

ragweed
ragweed allergy
allergy
allergies

allergic
1018 ISS
seasonal allergic rhinitis
allergic rhinitis

Additional relevant MeSH terms:

Rhinitis, Allergic, Seasonal
Rhinitis
Nose Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Otorhinolaryngologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

Respiratory Tract Infections
Histamine
Histamine phosphate
Histamine Agonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012