Efficacy/ Safety of Omalizumab in Patients With Seasonal Allergic Asthma and Seasonal Allergic Rhinoconjunctivitis

• ClinicalTrials.gov Identifier: NCT00396409
• Recruitment Status: Completed
• First Posted: November 7, 2006
• Results First Posted: June 3, 2011
• Last Update Posted: March 30, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

Efficacy/ safety for the combination of anti-IgE (Omalizumab) and specific immunotherapy (Depigoid) in patients with not adequately controlled seasonal allergic asthma and comorbid seasonal allergic rhinoconjunctivitis.

Condition or disease	Intervention/treatment	Phase
Allergic Asthma	Drug: Depigoid; Drug: Omalizumab; Drug: Placebo	Phase 3

Detailed Description:

This was an open-label extension period of the previously randomized, multicenter, double-blind, placebo-controlled, parallel-group trial to demonstrate the benefit of pre- and co-seasonal combination therapy with anti-IgE (omalizumab) and specific immunotherapy (Depigoid) in patients with seasonal allergic asthma and co-morbid seasonal allergic rhinoconjunctivitis. During the open-label period, all patients received Depigoid monotherapy for two follow-up seasons every 4 weeks, 26 injections in total. The extension period was performed to evaluate the influence of omalizumab on the follow-up treatment with Depigoid in seasonal asthma.

This study was a follow-up to the core IGE025ADE03 study, in which patients received omalizumab treatment. In this follow-up study, no patient received omalizumab.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, 20 Week, Double-blind, Placebo-controlled, Parallel-group, Multiple-dose, Multicenter Study to Assess the Efficacy and Safety of Omalizumab in Combination With Depigoid, Versus Depigoid Only, in Adult and Adolescent Patients With Seasonal Allergic Asthma and Comorbid Seasonal Allergic Rhinoconjunctivitis - Open-label Depigoid Monotherapy Extension Periods 2007 and 2008-
• Study Start Date: February 2006
• Actual Primary Completion Date: August 2008
• Actual Study Completion Date: August 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Depigold+Omalizumab; Xolair® (Omalizumab, double-blind core study period only), Depigoid® (grass/rye pollen 50/50)	Drug: Depigoid; Administered in 4-week intervals using 0.5 ml of vial 2 (1000 DPP/mL); Drug: Omalizumab; anti-IgE (Omalizumab) given during the 2006 core study; Other Name: Xolair
Experimental: Depigoid+Placebo; Depigoid® (grass/rye pollen 50/50) + Placebo	Drug: Depigoid; Administered in 4-week intervals using 0.5 ml of vial 2 (1000 DPP/mL); Drug: Placebo; Placebo given during the 2006 core study

Outcome Measures

Primary Outcome Measures :

1. Daily Symptom Load [ Time Frame: Recorded daily during the 2007 and 2008 pollen season ]
   The daily symptom load (low=0, high=unbounded) represents the daily combined asthma and rhinoconjunctivitis symptom severity scores plus the daily asthma rescue medication score based on patient diary entries. A higher score indicates a worse patient asthma condition. Symptoms (e.g. - difficulty breathing, cough, tightness of chest, sneezing, itchy nose, red eyes, etc.) were evaluated daily by the patient using a 4-point scale (0=no symptom, 1=mild, 2=moderate, 3=severe). Point values were assigned by specific rescue medication usage. The daily scores were averaged over pollen days by site.

Secondary Outcome Measures :

1. Asthma/Rhinoconjunctivitis Symptom Severity Score [ Time Frame: Recorded daily during the 2007 and 2008 pollen season ]
   The symptom severity score was defined as the mean of the daily symptom severity scores (asthma symptoms during the day, asthma symptoms at night, rhinitis symptoms, and conjunctivitis symptoms) during the pollen season. The daily symptom severity scores were evaluated daily by the patient using a 4-point scale (0 = none (no symptom), 1 = mild, 2 = moderate, 3 = severe) and were recorded in a patient diary. The possible minimum value for the Asthma/Rhinoconjunctivitis Symptom Severity Score is 0, and the possible maximum value is 3. Higher values represent a worse outcome.
2. Asthma/Rhinoconjunctivitis Rescue Medication Score [ Time Frame: Recorded daily during the 2007 and 2008 pollen season ]
   Asthma/Rhinoconjunctivitis rescue medication score is a component of symptom load. Patients were advised that between visits they could take short acting β-2 agonist rescue medication as initial rescue medication for symptoms of intercurrent bronchospasm. Patients were advised that between visits they could take rescue medication (systemic antihistamines) on an as-needed basis for symptoms of grass pollen allergic rhinoconjunctivitis. The symptom load and all its components were based on the patient's entries in their diaries.
3. Percentage of Participants by Global Evaluation of Treatment Effectiveness (GETE) Assessment Category Performed by the Investigator [ Time Frame: 52 Weeks (2007) and 104 Weeks (2008) after completion of core study ]
   The investigator's assessment of the global evaluation of treatment effectiveness (GETE) using a five point scale, which evaluates change in asthma control/symptoms. GETE is scored as 1='excellent', 2='good', 3='moderate', 4='poor', 5='worsening' and (.)='missing').
4. Percentage of Participants by Global Evaluation of Treatment Effectiveness (GETE) Assessment Category Performed by the Patient [ Time Frame: 52 Weeks (2007) and 104 Weeks (2008) after completion of core study ]
   The patient's assessment of the global evaluation of treatment effectiveness (GETE) using a five point scale, which evaluates change in asthma control/symptoms. GETE is scored as 1='excellent', 2='good', 3='moderate', 4='poor', 5='worsening' and (.)='missing').
5. Asthma Control Questionnaire (ACQ) [ Time Frame: 52 Weeks (2007) and 104 Weeks (2008) after completion of core study ]
   The Asthma Control Questionnaire (ACQ) was developed and validated for assessing asthma symptom control in patients in clinical trials as well as for individuals in clinical practice. It is a simple questionnaire consisting of seven questions assessing symptoms, airway caliber and rescue β2-agonist use. It uses a 7-point scale. The possible minimum value is 1, the possible maximum value is 7. Higher values represent worse asthma control and quality of life, respectively.
6. Asthma Quality of Life Questionnaire (AQLQ) [ Time Frame: 52 Weeks (2007) and 104 Weeks (2008) after completion of core study ]
   The Asthma Quality of Life Questionnaire (AQLQ) is a 32-item disease specific questionnaire designed to measure functional impairments that are most important to patients with asthma. It consists of 4 domains (symptoms, emotions, exposure to environmental stimuli and activity limitation). Patients are asked to recall their experiences during the previous 2 weeks and to score each item on a 7-point scale. The overall AQLQ score is the mean response to all 32 questions (low=1, high=7). Higher values represent better quality of life.
7. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) [ Time Frame: 52 Weeks (2007) and 104 Weeks (2008) after completion of core study ]
   The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) is a 28-item disease specific questionnaire designed to measure functional impairments that are most important to patients with rhinoconjunctivitis. It consists of 7 domains (activities, sleep, common complaints, practical problems, nasal symptoms, ocular symptoms, and emotions). Patients recall their experiences during the previous week and to score each item on a 7-point scale. The overall RQLQ score is the mean response to all 28 questions (low=1, high=7). Higher values represent worse quality of life.
8. Asthma Quality of Life Questionnaire (AQLQ) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) - Clinical Differences to Baseline [ Time Frame: Baseline of core study and 52 Weeks (2007) and 104 Weeks (2008) after completion of core study ]
   Both the AQLQ and RQLQ clinical differences were categorized as important, moderate, or meaningful improvement; no clinical change; meaningful, moderate, or important impairment. Clinically important differences in scores between any two assessments have been determined by the authors of the AQLQ and RQLQ. Changes in scores of 0.5 to 1.0 are considered clinically meaningful; 1.0 to 1.5 as moderate and > 1.5 as marked clinically important differences for any individual domain or for the overall summary score.
9. Work Productivity and Activity Impairment [ Time Frame: 52 Weeks (2007) and 104 Weeks (2008) after completion of core study ]
   The Work Productivity and Activity Impairment questionnaire measures time missed from work, impairment of work and regular activities. It consists of 6 items. The outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. The minimum value is 0 (0 %), the maximum value is 1 (100%). The recall time is 1 week. For this study WPAI-AA was used defining the specific health problem as allergic asthma, which has been validated by the instrument owner.
10. Lung Function as Assessed by Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Assist during 2007 and 2008 pollen season ]
    The spirometric parameter Forced Expiratory Volume in One Second (FEV1) was measured during grass pollen season before each injection of Depigoid.
11. Lung Function as Assessed by Peak Expiratory Flow (PEF) [ Time Frame: Assist during 2007 and 2008 pollen season ]
    The spirometric parameter Peak Expiratory Flow (PEF) was measured during grass pollen season before each injection of Depigoid. PEF was collected in the patient diary at seven days after visit 22, 23 and 24 as well as 35, 36 and 37. For analyzing purposes these data were averaged after the respective visits. Missing PEF-values from the patient diary were not replaced.

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 45 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males or females of any race who are 12-45 years of age with a body weight ≥ 20 kg and ≤ 150 kg and with a total serum IgE level ≥ 30 to ≤ 700 IU/ml (suitable weight for dosing)
• Patients with the diagnosis of not adequately controlled seasonal grass pollen (and/or rye pollen) and allergic asthma with concomitant seasonal allergic rhinoconjunctivitis within > 2 previous seasons
• patients with a positive RAST (>CAP2) result for grass pollen (and/or rye pollen) specific IgE at screening (Visit 1 (V1) or within the previous 12 months.
• Patients with FEV1 > 80% of the predicted normal value for the patient at screening [V1](demostrable at least 6 hours after last short acting B-2 agonist use or 12 hours after last long B-2 acting agonist use).

Exclusion Criteria:

• Females of childbearing potential: pregnancy, birth control,breast-feeding

• Concurrent diseases/conditions and history of other diseases/conditions

  1. patients who have a positive history of significant clinical manifestations of allergy as a result of sensitization against tree pollen allergens, weed allergens and perennial allergens (e.g. Aspergillus spores, animal dander, house dust mite).
  2. patients with a history of food or drug related severe anaphylactoid or anaphylactic reaction(s).

• Ingredient hypersensitivity

  1. patients with known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication, any immunotherapy, or drugs related to Omalizumab (e.g., monoclonal antibodies, polyclonal gamma globulin).
  2. patients with hypersensitivity to the trail's asthma rescue- or escalation-medication or related drugs.

Contacts and Locations

Locations

Germany

Novartis Investigator site

Nuremberg, Germany

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Chair: Novartis Pharmaceuticals; Novartis Pharmaceuticals, Basel +41 61 324 1111.

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00396409
• Other Study ID Numbers: CIGE025ADE03
• First Posted: November 7, 2006
• Results First Posted: June 3, 2011
• Last Update Posted: March 30, 2017
• Last Verified: February 2017

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Omalizumab; Anti-Allergic Agents; Anti-Asthmatic Agents; Respiratory System Agents