E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of lebrikizumab in reducing airway eosinophilic inflammation, as measured by a relative change in the number of airway submucosal eosinophils per surface area of basal lamina (cells/mm2) obtained via endobronchial biopsy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of lebrikizumab on airway eosinophilic inflammation, as measured by:- absolute change in the number of airway submucosal eosinophils per surface area of basal lamina (cells/mm2) obtained via endobronchial biopsy- relative and absolute changes in the number of airway epithelial eosinophils per surface area of basal lamina (cells/mm2) obtained via endobronchial biopsy- relative and absolute changes in number of airway submucosal eosinophils per volume of submucosa (cells/mm3) obtained via endobronchial biopsy- relative and absolute changes in number of airway epithelial eosinophils per volume of epithelium (cells/mm3) obtained via endobronchial biopsy.
To evaluate the effect of lebrikizumab on serum periostin, IL-13-related and asthma-related (airway and blood) biomarkers including fractional exhaled nitric oxide (FeNO.)
To evaluate the efficacy of lebrikizumab, as measured by the relative change in prebronchodilator forced expiratory volume in 1 second (FEV1). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MINIMALLY-INVASIVE AIRWAY BIOMARKER SUBSTUDY IN ASSOCIATION WITH LEBRIKIZUMAB STUDY GB29260: A PHASE II, RANDOMIZED, DOUBLE‑BLIND, PLACEBO-CONTROLLED BRONCHOSCOPY STUDY TO EVALUATE THE EFFECTS OF LEBRIKIZUMAB ON AIRWAY EOSINOPHILIC INFLAMMATION IN PATIENTS WITH UNCONTROLLED ASTHMA ON INHALED CORTICOSTEROIDS AND A SECOND CONTROLLER MEDICATION
version 2, 29 September 2015
The objectives of this substudy are considered exploratory and are as follows:
•To evaluate the effect of lebrikizumab in reducing sputum eosinophils
•To evaluate the effects of lebrikizumab on asthma pathway related biomarkers in nasal mucosal lining fluid (MLF)
•To evaluate serum, sputum, and nasal MLF lebrikizumab concentrations, if feasible
•To evaluate the ability of serum periostin, fractional exhaled nitrous oxide (FeNO), and blood eosinophil counts to predict the effect of lebrikizumab on sputum eosinophils
•To evaluate the ability of serum periostin, FeNO and blood eosinophil counts to predict the effect of lebrikizumab on asthma pathway related biomarkers in nasal MLF
•To compare asthma pathway related biomarkers in nasal MLF with those obtained via endobronchial biopsy
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E.3 | Principal inclusion criteria |
- Age 18-75 years old at study start
- Asthma diagnosis for >/= 12 months prior to study start
- Documented Bronchodilator Reversibility within past 12 months or during screening
- Pre-bronchodilator FEV1 of 40% - 80% predicted at both screening visits 2 and 3
- On ICS therapy at a total daily dose of 500-2000 ug of fluticasone propionate dry powder inhaler (DPI) or equivalent for >/= 6 months prior to study start, with no changes within 4 weeks prior, and no anticipated changes throughout the study
- On an eligible second controller medication (LABA, LTRA, LAMA, or theophylline) for 6 months prior to study start, with no changes within 4 weeks prior, and no anticipated changes throughout the study
- Uncontrolled asthma at screenings visits 1 and/or 2, and at visit 3
- Chest X-ray or computed tomography (CT) scan within 12 months prior to Visit 1 or chest X-ray during the screening period that confirms the absence of other clinically significant lung disease
- Demonstrated adherence with controller medication during the screening period
- Use of effective contraception, as defined by the protocol, until 24 weeks after the last dose
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E.4 | Principal exclusion criteria |
- Maintenance oral corticosteroid therapy, defined as daily or alternate-day oral corticosteroid maintenance therapy within 3 months prior to study start
- Treatment with systemic corticosteroids within 4 weeks prior to study start or during the screening period for any reason
- Any infection requiring hospital, IV or IM antibiotic treatment or any respiratory infection within 4 weeks of study start or during screening. Any infection requiring oral antibiotic treatment with 2 weeks of study start, or any parasitic infection within 6 months of study start or during screening
- Active tuberculosis requiring treatment within 12 months prior to study start or during screening
- Known immunodeficiency, including, but not limited to, HIV infection
- History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma
- Known current malignancy or current evaluation for a potential malignancy
- Unable to safely undergo elective flexible fiberoptic bronchoscopy
- Clinically significant abnormality found during screening or clinically significant medical disease that is uncontrolled despite treatment, that is likely, in the opinion of the investigator, to impact the patient's ability to participate in the study, or impact the study assessments
- History of alcohol or drug abuse that would impair or risk the patients full participation in the study, in the opinion of the investigator
- Current or history of smoking ( > 10 pack-years), or unwillingness to abstain from smoking for the duration of the study
- Past and/or current use of any anti-IL-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
- Use of a licensed or investigational monoclonal antibody other than anti-IL-13 or anti-IL-4/IL-13, including, but not limited to, omalizumab, anti-IL-5, or anti-IL-17, within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
- Use of a systemic immunomodulatory or immunosuppressive therapy within 3 months or 5 drug half-lives prior to study start or during screening
- Use of other investigational therapy within 4 weeks or 5 drug half-lives prior to study start (whichever is longer) or during screening
- Initiation of or increase in allergen immunotherapy within 3 months prior to study start or during screening
- Body mass index > 38 kg/m2
- Body weight < 40 kg
- History of bronchial thermoplasty
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E.5 End points |
E.5.1 | Primary end point(s) |
Relative change in number of airway submucosal eosinophils per surface area of basal lamina (cells/mm2)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Absolute change in number of airway submucosal eosinophils per surface area of basal lamina (cells/mm2)
2. Relative change in the number of airway epithelial eosinophils per surface area of basal lamina (cells/mm2)
3. Absolute change in the number of airway epithelial eosinophils per surface area of basal lamina (cells/mm2)
4. Relative change in number of airway submucosal eosinophils per volume of submucosa (cells/mm3)
5. Absolute change in number of airway submucosal eosinophils per volume of submucosa (cells/mm3)
6. Relative change in number of airway epithelial eosinophils per volume of epithelium (cells/mm3)
7. Absolute change in number of airway epithelial eosinophils per volume of epithelium (cells/mm3)
8. Changes in asthma-related biomarkers
9. Change in lung epithelial cell gene expression
10. Relative change in fractional exhaled nitric oxide (FeNO)
11. Relative change in forced expiratory volume in 1 second (FEV1)
12. Incidence of adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 to 11. From Baseline to Week 12
12. Up to week 20 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Ireland |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 29 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 31 |
E.8.9.2 | In all countries concerned by the trial days | 0 |