Status:Not yet recruiting
Specialty:Allergy and Clinical Immunology
Sub Specialty:Environmental Allergy
The purpose of this study is to collect efficacy and safety data in asthma patients not adequately controlled with high-dose ICS plus long-acting β2-agonist who are receiving QGE031(study drug), omalizumab or placebo. The study is designed to determine if QGE031 is superior to placebo, when added to high daily dose ICS plus LABA (Global Initiative for Asthma GINA step 4).
Asthma control will be the primary endpoint using the Asthma Control Questionnaire (ACQ). The study will also allow comparison of the safety and efficacy of QGE031 compared to omalizumab in this population.
Data collected during this study will be used to support decision making related to further development
of QGE031 for the asthma indication. The study will also provide data to aid selection of doses for
further evaluation and provide information on patient reported outcome (PRO) tools and potential
biomarkers which may be included in future studies.
To evaluate the efficacy of QGE031 240 mg s.c. every two weeks compared to matched placebo when
added to existing asthma therapy by comparing the responder rates* following 16 weeks treatment in
patients inadequately controlled** on high dose inhaled corticosteroids plus long-acting β2agonists
(GINA treatment step 4).
Key secondary objective:
To evaluate the superiority of QGE031 240 mg s.c. every two weeks compared to omalizumab
(administered as per locally approved dosing tables) when added to existing asthma therapy by
comparing the responder rates* following 16 weeks treatment in patients inadequately controlled** on
high dose inhaled corticosteroids plus long-acting β2agonists (GINA treatment step 4).
* Response is defined as a decrease of 0.5 or more of the ACQ7 score from baseline)
**Inadequate control is defined as an ACQ7 score of ≥1.5 at the end of the run-in epoch (Juniper et al,
Other Secondary Objective:
Exploratory pharmacogenetics research studies are planned as a part of this study with the
objectives of identifying inherited genetic factors which may (1) be related to asthma, (2)
predict response to treatment with QGE031, (3) predict relative susceptibility to drug-drug
interactions, or (4) predict genetic predisposition to side effects. We hope to develop a better
understanding of asthma and how subjects respond to QGE031.
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
For all patients (treatment arms A to G):
1. Signed written informed consent before any assessment is performed, including any adjustments to asthma medication at Visit 1.
2. Male and female adult patients aged ≥ 18 -≤75 years.
3. Patients with a diagnosis of asthma (according to GINA 2011 guidelines) for a period of at least 24 months prior to Visit 1.
4. A documented history of two asthma exacerbation(s) in the previous 24 months (with one episode occurring within the last 12 months). Both episodes of asthma exacerbation must
have documented treatment with systemic corticosteroids for at least 3 days.
5. FEV1 of ≥ 40% and ≤ 80% of the predicted normal value for the patient, after withholding bronchodilators1.
6. Patients must demonstrate an increase in FEV1 of ≥12% and 200 mLs within 30 minutes after administration of 400 μg salbutamol/albuterol (or equivalent dose) prior to randomization2.
• All patients must perform a reversibility test at Visit 101
If reversibility is not demonstrated at Visit 101:
• Patients may be permitted to enter the study with historical evidence of reversibility that was performed according to ATS/ERS guidelines within the 12 months prior to Visit 12.
If reversibility is not demonstrated at Visit 101 and historical evidence of reversibility is not available (or was not performed according to ATS/ERS guidelines):
• The reversibility test may be repeated on one occasion at an unscheduled visit prior to randomization.
7. Body mass index (BMI) must be within the range of 18 to 35 kg/m2 inclusive.
8. Daily treatment with:
• At Visit 1: Medium or high dose3 ICS plus a LABA (b.i.d.) for ≥ 3 months prior to Visit 1*, and
• At Visit 201: High dose ICS3 plus a LABA (b.i.d.) that has been stable for at least 4 weeks prior to Visit 201.
See Appendix 3 for definitions of “Medium” and “High” dose ICS (per GINA 2011)
*Patients receiving medium dose ICS at Visit 1 should be up-titrated to high dose ICS at Visit 101; this dose should then remain stable during the 4 week run-in epoch prior to Visit 201.
9. Asthma which is not adequately controlled on current treatment, as demonstrated by an Asthma Control Questionnaire (ACQ) score of ≥ 1.5 (Juniper et al, 2006) at Visit 101 and
prior to randomization.
10. Patients should be allergic or atopic to a perennial aeroallergen (house dust mite [dermatophagoides pteronyssinus, dermatophagoides farina], cockroach, mold, cat/dogdander), as diagnosed at Visit 101, prior to entry into the study, by either a skin prick test (≥ 3mm diameter above background) or a positive in-vitro specific IgE (e.g. RAST/CAP) test.
11. Compliance with Electronic Peak Flow/ ediary device4 during the screening epoch (at the investigators judgment the run-in epoch can be extended to collect 14 days of acceptable ePEF/ediary data).
1 Withholding of bronchodilators prior to spirometry: short-acting β2-agonist for ≥ 6 hrs and long-acting beta2-agonist (or fixed dose combinations of LABA and ICS) for ≥ 24 hours.
2 Where a patient is assessed as eligible based on historical evidence of reversibility, a copy of the original printed spirometry report with relevant spirometry tracings must be available as source documentation.
3 See Appendix 3 for GINA 2011 definition of medium and high dose ICS.
4 Compliance is defined as ≥ 85% of the ePEF assessments and ≥ 85% of the morning or evening ediary entries completed correctly in the 14 days prior to the randomization. Thresholds will be automatically calculated by the ePEF/ediary device.
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No
additional exclusions may be applied by the investigator, in order to ensure that the study
population will be representative of all eligible patients.
For all patients (treatment arms A to G):
1. Patients whose baseline serum IgE levels1 or body weight are outside the limits of the
locally approved omalizumab dosing table.
1See Section 220.127.116.11 for definition of baseline serum IgE and refer to relevant locally
approved omalizumab dosing table in the QGE031B2201 study manual.
2. Who have smoked or inhaled tobacco products within the 6 month period prior to Visit 1,
or who have a smoking history of greater than 10 pack years (e.g.10 pack years = 1 pack
/day x 10 yrs., or ½ pack/day x 20 yrs.).
3. Who have had an asthma attack/exacerbation requiring a short burst of systemic
corticosteroids for at least 3 days within 6 weeks prior to Visit 1.
4. If patients experience an asthma attack/exacerbation requiring a short burst of systemic
corticosteroids during screening and run-in they may be re screened 6 weeks after
recovery from the exacerbation.
5. Who have had a respiratory tract infection or asthma worsening within 4 weeks prior to
6. If patients experience a respiratory tract infection or asthma worsening during screening
and run-in they may be re screened 4 weeks after recovery from their respiratory tract
7. Patients with a history of life-threatening asthma, including a history of significant
hypercarbia (pCO2>45mmHg), prior intubation (endotracheal and NIPPV), respiratory
arrest, or seizures as a result of asthma.