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

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-

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00396409

Enrollment

128

Registered

2006-11-07

Start date

2006-02-28

Completion date

2008-08-31

Last updated

2017-03-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Allergic Asthma

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.

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.

Interventions

DRUGDepigoid

Administered in 4-week intervals using 0.5 ml of vial 2 (1000 DPP/mL)

DRUGOmalizumab

anti-IgE (Omalizumab) given during the 2006 core study

DRUGPlacebo

Placebo given during the 2006 core study

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

12 Years to 45 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Daily Symptom Load	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

Measure	Time frame	Description
Asthma/Rhinoconjunctivitis Rescue Medication Score	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.
Percentage of Participants by Global Evaluation of Treatment Effectiveness (GETE) Assessment Category Performed by the Investigator	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').
Percentage of Participants by Global Evaluation of Treatment Effectiveness (GETE) Assessment Category Performed by the Patient	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').
Asthma Control Questionnaire (ACQ)	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.
Asthma Quality of Life Questionnaire (AQLQ)	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.
Asthma/Rhinoconjunctivitis Symptom Severity Score	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.
Asthma Quality of Life Questionnaire (AQLQ) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) - Clinical Differences to Baseline	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.
Work Productivity and Activity Impairment	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.
Lung Function as Assessed by Forced Expiratory Volume in One Second (FEV1)	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.
Lung Function as Assessed by Peak Expiratory Flow (PEF)	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.
Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)	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.

Countries

Germany

Participant flow

Participants by arm

Arm	Count
Depigoid + Omalizumab Depigoid administered in 4-week intervals using 0.5 ml of vial 2 (1000 DPP/mL). Omalizumab was given during the 2006 core study.	65
Depigoid + Placebo Depigoid dministered in 4-week intervals using 0.5 ml of vial 2 (1000 DPP/mL). Placebo was given during the 2006 core study	63
Total	128

Withdrawals & dropouts

Period	Reason	FG000	FG001
Between Period 1 and Period 2	Withdrawal by Subject	3	2
Period 1 - 2007	Adverse Event	0	1
Period 1 - 2007	Lack of Efficacy	0	1
Period 1 - 2007	Lost to Follow-up	2	3
Period 1 - 2007	Withdrawal by Subject	1	1
Period 2 - 2008	Lost to Follow-up	3	1
Period 2 - 2008	Protocol Violation	1	0
Period 2 - 2008	Withdrawal by Subject	3	1

Baseline characteristics

Characteristic	Total	Depigoid + Omalizumab	Depigoid + Placebo
Age, Continuous 2007	29.1 years STANDARD_DEVIATION 10.3	27.8 years STANDARD_DEVIATION 9.9	30.4 years STANDARD_DEVIATION 10.6
Age, Continuous 2008 (N = 59/55/114)	28.8 years STANDARD_DEVIATION 10.5	27.6 years STANDARD_DEVIATION 9.9	30.1 years STANDARD_DEVIATION 10.9
Age, Customized <= 18 years	29 participants	14 participants	15 participants
Age, Customized <=18 years	30 participants	15 participants	15 participants
Age, Customized >= 65 years	0 participants	0 participants	0 participants
Age, Customized >=65 years	0 participants	0 participants	0 participants
Age, Customized Between 18 and 65 years	98 participants	50 participants	48 participants
Age, Customized Participated in 2007 but not in 2008	14 participants	6 participants	8 participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants	0 participants	0 participants
Race/Ethnicity, Customized Asian	1 participants	0 participants	1 participants
Race/Ethnicity, Customized Black or African American	0 participants	0 participants	0 participants
Race/Ethnicity, Customized More than one race	0 participants	0 participants	0 participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants	0 participants	0 participants
Race/Ethnicity, Customized Participated in 2007 but not in 2008	14 participants	6 participants	8 participants
Race/Ethnicity, Customized Unknown or Not Reported	0 participants	0 participants	0 participants
Race/Ethnicity, Customized White	113 participants	65 participants	62 participants
Sex/Gender, Customized 2007 Female	55 participants	28 participants	27 participants
Sex/Gender, Customized 2007 Male	73 participants	37 participants	36 participants
Sex/Gender, Customized 2008 Female	50 participants	24 participants	26 participants
Sex/Gender, Customized 2008 Male	64 participants	35 participants	29 participants
Sex/Gender, Customized Participated in 2007 but not in 2008	14 participants	6 participants	8 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	36 / 65	32 / 59	34 / 63	26 / 55
serious Total, serious adverse events	2 / 65	5 / 59	2 / 63	1 / 55

Outcome results

Primary

Daily Symptom Load

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.

Time frame: Recorded daily during the 2007 and 2008 pollen season

Population: Intent-to-Treat (ITT). The complete analysis population who consisted of all patients that received at least one dose of study drug was used for all efficacy and safety evaluations in this extension period.

Arm	Measure	Group	Value (MEAN)	Dispersion
Depigoid + Omalizumab	Daily Symptom Load	2007	1.25 units on a scale	Standard Deviation 0.99
Depigoid + Omalizumab	Daily Symptom Load	2008	1.32 units on a scale	Standard Deviation 1.74
Depigoid + Placebo	Daily Symptom Load	2007	1.10 units on a scale	Standard Deviation 0.99
Depigoid + Placebo	Daily Symptom Load	2008	0.97 units on a scale	Standard Deviation 1.02

Secondary

Asthma Control Questionnaire (ACQ)

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.

Time frame: 52 Weeks (2007) and 104 Weeks (2008) after completion of core study