Study to Assess the Efficacy and Safety of Omalizumab Treatment on ICS Reduction for Severe IgE-mediated Asthma

Multicentric, Open-label, Randomized, Parallel--group Study to Evaluate the Efficacy and Safety of Omalizumab in a 12- Month Period, in Patients With Severe IgE-mediated Asthma Inadequately Controlled With High Doses of Corticosteroids.

Status

Terminated

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01912872

Acronym

MEXIC

Enrollment

112

Registered

2013-07-31

Start date

2013-11-11

Completion date

2016-01-08

Last updated

2019-07-02

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

Conditions

Severe IgE-mediated Asthma

Brief summary

Assess efficacy and safety of omalizumab treatment during 12 months in order to reduce the use of inhaled corticosteroid (ICS) in pediatric and adult participants with severe Immunoglobulin E (IgE)-mediated asthma inadequately controlled with high doses of corticosteroids.

Detailed description

This was a multicentric, open label, randomized, parallel-group study with a 12-month treatment period. Participants were assigned to one of the 2 treatment groups, omalizumab plus budesonide/formoterol or budesonide/formoterol alone. The study comprised 4 phases: During the 4-week run-in phase adult participants received budesonide 800 mg and formoterol 24 mg. If a participant complied with all inclusion and exclusion criteria and had received the according-to-age run-in proposed doses during the last month, the participant continued to the stable-steroid phase. During the 16-week stable-steroid phase, adult and pediatric eligible participants were randomized to one of the two treatment groups. During the 8-week steroid-reduction phase, adult and pediatric participants reduced 25% of the budesonide baseline dose every 2 weeks, depending of the asthma control, until they reached a 100% reduction of the baseline dose. The clinical control of asthma was defined according to criteria (GINA 2012).

Interventions

DRUGOmalizumab

Subcutaneous injection dose according to the IgE level and body weight.

DRUGBudesonide

Budesonide (400 μg, 200 μg or 100 μg) tablets taken orally according to maximum daily dose.

DRUGFormoterol

Formoterol 12ug tablets taken orally according to maximum daily dose.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

6 Years to 55 Years

Healthy volunteers

Inclusion criteria

* Male and female between 6 and 55 years old. If female, participant of childbearing potential must use a safe and efficacious birth control method. * Asthma is considered as not well-controlled if participant has 3 or more of the following conditions: 1. Persistent day symptoms with current therapy twice at week or more, (siblings, dyspnea, cough, chest pain, thoracic oppression). 2. One or more night-time awakenings over the last 4 weeks. 3. Any limitation of age-appropriated habitual activities. 4. Need of rescue medication (short acting β2 agonist) for two or more occasions per week during the last 4 weeks before screening and 2 consecutive weeks within the 4 weeks before selection. 5. Peak expiratory flow (PEF) or VEF1 \<80% predicted or personal best (if known) this is not mandatory for pediatric participants (under 18 years old). * Despite continuous treatment with high-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) (CSO≥ 1 mg/kg/day) with or without controllers (As per GINA 2012 definition), the subject is receiving high doses of ICS (budesonide or its equivalent) and a long-acting β2-agonists(LABA) (formoterol) for the past 12 weeks at visit 0. * At last one documented asthma exacerbation (defined as increase asthma symptoms requiring systemic corticosteroid rescue therapy) that requires visits to the emergency room or to be hospitalized in the past 12 months. It is also considered asthma exacerbation a non-planned visit that required rescue medication (β2-agonists and/or steroid nebulization every 20 minutes or β2-agonists inhaler shots every 20 minutes). * Positive skin test or in vitro reactivity to a perennial aeroallergen, documented during the 12 months previous screening. * IgE total concentration ranging from 30 to 1500 UI/ml. * Body weight between 20 to 150 kg

Exclusion criteria

* Pregnant or lactating female or without safe and efficacious birth control method if of childbearing potential. * Currently smokers or history of smoking 10 or more packs per year. * Ex-smokers with a history of more than 10 years of smoking. As an exception, a participant with this criterion will be considered as eligible if the FEV1 reversibility of the first spirometry reaches 12%. * Active lung disease other than asthma. * Use of methotrexate, gold salts, troleandomycin, cyclosporine, immunosuppressants, gammaglobulin or any other type of monoclonal antibody used during the 6 months prior to the initial visit. * Use of omalizumab during the 4 months prior to de screening visit. * History of renal disease, cardiovascular disease, metabolic disease, hematologic disease, gastrointestinal disease, as well as immunodeficiency or cerebrovascular disease currently under treatment but not-controlled. * History of hepatic, neurologic, oncologic or autoimmune disease. * Participant under suspicion of having cancer. * Participants with history of hypersensitivity to sucrose, histidine, polysorbate 20 as well as to monoclonal antibodies or gammaglobulin. * Hypersensitivity to omalizumab or its excipients. * Abnormal values of the blood chemistry laboratory tests, over 2 times the upper limit normal, that are considered clinically significant. * Underage participant or any participant under vulnerable conditions who does not live with their parents or legal guardian.

Design outcomes

Primary

Measure	Time frame	Description
The Mean Prescribed Budesonide Dose (μg) at Baseline	Baseline	prescribed budesonide dose (in μg) at Baseline in intention to treat population and in intention to treat population

Secondary

Measure	Time frame	Description
Days Missed in School/Work Due to Asthma Exacerbation Episodes	12 month treatment duration	Participants /parent/legal guarding reported number of missed days of school or work at each study visit via diaries.
Control of Asthma Symptoms- Daytime Symptoms	12 month treatment duration	The clinical control of asthma was defined according to the following criteria (GINA 2012): 1-Daytime symptoms: none or less than twice a week 2-Limitations of daily activities: none 3-Nocturnal symptoms or awakening because of asthma: none 4-Need of relief or rescue medication: none or less than twice a week 5-Lung function (PEF or FEV1) without administration of bronchodilator: normal
Control of Asthma Symptoms	12 month treatment duration	The clinical control of asthma was defined according to the following criteria (GINA 2012): 1-Daytime symptoms: none or less than twice a week 2-Limitations of daily activities: none 3-Nocturnal symptoms or awakening because of asthma: none 4-Need of relief or rescue medication: none or less than twice a week 5-Lung function (PEF or FEV1) without administration of bronchodilator: normal
Number of Hospital Admissions Due to Asthma Exacerbation	12 month treatment duration	A hospital admission is defined as admissions to hospital involving a stay of at least 24 hours.
Participants Requiring Oral Systemic Corticosteroids During the 12 Month Study Duration	12 month treatment duration	Number of days of concomitant medications use reported by participants at all visits via diaries.
Asthma Control Questionnaire (ACQ) at Baseline	Baseline	The Asthma Control Questionnaire (ACQ) has six questions to be answered by the participants, each with a 7 point scale (0-good control, 6-poor control), and one question where the actual pre-bronchodilator Forced expiratory volume in 1 second (FEV1) value expressed in % of predicted FEV1 was classified to scores from 0 (\> 95% of predicted) to 6 (\< 50% of predicted). The overall score is the average of the 7 questions; a minimum overall score of 0 = good control of asthma whereas a maximum overall score of 6 = poor control of asthma.
Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Baseline	The quality of life will be measured by the standardized version of the Asthma Quality of Life Questionnaire (AQLQ\[S\]) score for adults and the pediatric version of the AQLQ(S) for pediatric participants (PAQLQ\[S\]) . The AQLQ(S) and PAQLQ(S0 contain 4 domains (activity limitations, symptoms, emotional function, and environmental stimuli), with a total of 32 items; each item is measured in a 7-point Likert scale of 1 to 7 (1 = severe impairment, 7 = no impairment). All items are weighted equally. Mean score is calculated across all items within each domain and the overall score is the mean score of the 32 items.
Control of Asthma Symptoms- Rescue Medication Use	12 month treatment duration	The clinical control of asthma was defined according to the following criteria (GINA 2012): 1-Daytime symptoms: none or less than twice a week 2-Limitations of daily activities: none 3-Nocturnal symptoms or awakening because of asthma: none 4-Need of relief or rescue medication: none or less than twice a week 5-Lung function (PEF or FEV1) without administration of bronchodilator: normal

Countries

Mexico

Participant flow

Participants by arm

Arm	Count
Pediatric Patients: Omalizumab + Budesonide and Formoterol Participants received omalizumab injection for s.c. use 2 or 4 weeks according to the IgE level and body weight and budesonide + formoterol administered through an inhaler device.	16
Pediatric Patients: Budesonide and Formoterol Participants received budesonide + formoterol administered through an inhaler device.	17
Adult Patients: Omalizumab + Budesonide and Formoterol Participants received Omalizumab every 2 or 4 weeks as a subcutaneous injection dose according to the IgE level and body weight. Participants also received and budesonide + formoterol administered through an inhaler device.	40
Adult Patients: Budesonide and Formoterol Participants receive budesonide + formoterol administered through an inhaler device.	39
Total	112

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Informed consent withdrawn	0	0	1	1
Overall Study	Lost to Follow-up	2	3	5	5
Overall Study	Missing	0	0	0	1
Overall Study	Non-compliance with lab inc/exclusion	0	0	0	1
Overall Study	Other unspecified	3	1	3	0
Overall Study	Protocol Violation	0	0	1	0
Overall Study	Unsatisfactory therapeutic effect	0	0	0	2
Overall Study	Withdrawal of study medication	0	0	0	2

Baseline characteristics

Characteristic	Pediatric Patients: Omalizumab + Budesonide and Formoterol	Pediatric Patients: Budesonide and Formoterol	Adult Patients: Omalizumab + Budesonide and Formoterol	Adult Patients: Budesonide and Formoterol	Total
Age, Continuous	11.1 years STANDARD_DEVIATION 3.32	12.4 years STANDARD_DEVIATION 1.8	37.6 years STANDARD_DEVIATION 10.01	38.7 years STANDARD_DEVIATION 10.3	30.4 years STANDARD_DEVIATION 14.84
Sex: Female, Male Female	6 Participants	8 Participants	28 Participants	28 Participants	70 Participants
Sex: Female, Male Male	10 Participants	9 Participants	12 Participants	11 Participants	42 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	11 / 16	7 / 17	27 / 40	21 / 39
serious Total, serious adverse events	1 / 16	2 / 17	2 / 40	1 / 39

Outcome results

Primary

The Mean Prescribed Budesonide Dose (μg) at Baseline

prescribed budesonide dose (in μg) at Baseline in intention to treat population and in intention to treat population

Time frame: Baseline

Population: Pediatric and Adult intent-to-treat (ITT) and per protocol (PP) populations. ITT population received at least one dose of study drug and one post-baseline assessment of the primary/secondary efficacy variables. PP population was participants that completed 12 months of treatment, had a valid assessment of the primary efficacy variable at Week 24.

Arm	Measure	Group	Value (MEAN)	Dispersion
Pediatric Patients: Omalizumab + Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	ITT	337.5 μg	Standard Deviation 95.74
Pediatric Patients: Omalizumab + Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	PP	363.6 μg	Standard Deviation 80.9
Pediatric Patients: Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	PP	250.0 μg	Standard Deviation 90.45
Pediatric Patients: Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	ITT	270.6 μg	Standard Deviation 98.52
Adult Patients: Omalizumab + Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	ITT	580.0 μg	Standard Deviation 201.53
Adult Patients: Omalizumab + Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	PP	575.0 μg	Standard Deviation 201.61
Adult Patients: Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	ITT	533.3 μg	Standard Deviation 248.5
Adult Patients: Budesonide and Formoterol	The Mean Prescribed Budesonide Dose (μg) at Baseline	PP	533.3 μg	Standard Deviation 258.2

Secondary

Asthma Control Questionnaire (ACQ) at Baseline

The Asthma Control Questionnaire (ACQ) has six questions to be answered by the participants, each with a 7 point scale (0-good control, 6-poor control), and one question where the actual pre-bronchodilator Forced expiratory volume in 1 second (FEV1) value expressed in % of predicted FEV1 was classified to scores from 0 (\> 95% of predicted) to 6 (\< 50% of predicted). The overall score is the average of the 7 questions; a minimum overall score of 0 = good control of asthma whereas a maximum overall score of 6 = poor control of asthma.

Time frame: Baseline

Population: Number of participants with a baseline measurement within the ITT Pediatric and Adult population.

Arm	Measure	Value (MEAN)	Dispersion
Pediatric Patients: Omalizumab + Budesonide and Formoterol	Asthma Control Questionnaire (ACQ) at Baseline	3.3 scores on a scale	Standard Deviation 1.31
Pediatric Patients: Budesonide and Formoterol	Asthma Control Questionnaire (ACQ) at Baseline	3.3 scores on a scale	Standard Deviation 1.26
Adult Patients: Omalizumab + Budesonide and Formoterol	Asthma Control Questionnaire (ACQ) at Baseline	3.6 scores on a scale	Standard Deviation 1.09
Adult Patients: Budesonide and Formoterol	Asthma Control Questionnaire (ACQ) at Baseline	3.3 scores on a scale	Standard Deviation 1.35

Secondary

Asthma Quality of Life Questionnaire (AQLQ) at Baseline

The quality of life will be measured by the standardized version of the Asthma Quality of Life Questionnaire (AQLQ\[S\]) score for adults and the pediatric version of the AQLQ(S) for pediatric participants (PAQLQ\[S\]) . The AQLQ(S) and PAQLQ(S0 contain 4 domains (activity limitations, symptoms, emotional function, and environmental stimuli), with a total of 32 items; each item is measured in a 7-point Likert scale of 1 to 7 (1 = severe impairment, 7 = no impairment). All items are weighted equally. Mean score is calculated across all items within each domain and the overall score is the mean score of the 32 items.

Time frame: Baseline

Population: Number of participants with a baseline measurement within the ITT Pediatric and Adult population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Pediatric Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Environmental stimuli domain	NA scores on a scale	—
Pediatric Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Emotional functions domain	3.2 scores on a scale	Standard Deviation 1.47
Pediatric Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Overall	3.2 scores on a scale	Standard Deviation 1.21
Pediatric Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Symptoms domain	3.2 scores on a scale	Standard Deviation 1.49
Pediatric Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Activity limitations domain	3.2 scores on a scale	Standard Deviation 1.18
Pediatric Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Activity limitations domain	3.3 scores on a scale	Standard Deviation 1.47
Pediatric Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Overall	3.4 scores on a scale	Standard Deviation 1.54
Pediatric Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Symptoms domain	3.3 scores on a scale	Standard Deviation 1.48
Pediatric Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Emotional functions domain	3.6 scores on a scale	Standard Deviation 1.76
Pediatric Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Environmental stimuli domain	NA scores on a scale	—
Adult Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Emotional functions domain	2.5 scores on a scale	Standard Deviation 1.16
Adult Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Environmental stimuli domain	2.7 scores on a scale	Standard Deviation 1.24
Adult Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Symptoms domain	2.8 scores on a scale	Standard Deviation 1.16
Adult Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Activity limitations domain	3.2 scores on a scale	Standard Deviation 1.07
Adult Patients: Omalizumab + Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Overall	2.9 scores on a scale	Standard Deviation 1.04
Adult Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Environmental stimuli domain	3.1 scores on a scale	Standard Deviation 1.47
Adult Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Overall	3.4 scores on a scale	Standard Deviation 1.25
Adult Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Activity limitations domain	3.5 scores on a scale	Standard Deviation 1.25
Adult Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Emotional functions domain	3.2 scores on a scale	Standard Deviation 1.49
Adult Patients: Budesonide and Formoterol	Asthma Quality of Life Questionnaire (AQLQ) at Baseline	Symptoms domain	3.5 scores on a scale	Standard Deviation 1.37

Secondary

Control of Asthma Symptoms

The clinical control of asthma was defined according to the following criteria (GINA 2012): 1-Daytime symptoms: none or less than twice a week 2-Limitations of daily activities: none 3-Nocturnal symptoms or awakening because of asthma: none 4-Need of relief or rescue medication: none or less than twice a week 5-Lung function (PEF or FEV1) without administration of bronchodilator: normal