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The main objective of the trial is to explore if any of the biomarkers assessed are sensitively linked to the asthma phenotypes. This would potentially alone or in addition to other clinical or biofluid markers indicate if and how asthma endotypes are linked to phenotype such as eosinophilic, neutrophilic, or paucigranulocytic phenotypes. Further exploratory markers will be analysed for better understanding of physiological levels of proteins and markers playing a role in regard to disease characterization in asthma. As a basis for further development of a biomarker for asthma, The sponsor plans to conduct this exploratory biomarker trial to determine levels and reference ranges of biomarkers potentially associated with asthma phenotypes. The trial aims at generating a panel of serum biomarkers that can be evaluated in subsequent interventional studies. The longitudinal design will be used to ascertain stability and test-retest reliability.
Purpose:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy subjects |
| ||
| Mild asthma | |||
| Moderate asthma | |||
| Severe asthma |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biofluid sampling | Procedure |
|
| Measure | Description | Time Frame |
|---|---|---|
| Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Baseline (Visit 1) | Level of Tumour Necrosis Factor-alpha (TNF-α) [picograms per milliliter (pg/mL)] in blood at baseline (Visit 1) is presented. | Baseline (Visit 1) |
| Level of Interleukin-6 (IL-6) in Blood at Baseline (Visit 1) | Level of Interleukin-6 (IL-6) (pg/mL) in blood at baseline (Visit 1) is presented. | Baseline (Visit 1) |
| Measure | Description | Time Frame |
|---|---|---|
| Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | Level of Tumour Necrosis Factor-alpha (TNF-α) (pg/mL) in blood at follow-up visit 28 days after baseline (Visit 2) is presented. | follow-up visit 28 days after baseline (Visit 2) |
| Level of Interleukin-6 (IL-6) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) |
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Inclusion criteria:
Body mass index (BMI) >=18 and <= 40 Non-smokers or ex-smokers with a cigarette smoking history of <= 10 pack years and smoking cessation for at least one year prior to enrolment Able to perform all trial related procedures including acceptable spirometry and production of induced sputum samples
Additional inclusion criteria for subject with asthma:
A minimum of one year history of asthma (physician diagnosed). Forced Expiratory Volume in one second (FEV1) reversibility of at least 12% above baseline at screening, unless documented in prior 12 months Methacholine response: concentration of <=8mg/ml to decrease FEV1 by 20% (PC20) at screening, unless documented in prior 12 months Stable asthma treatment for a period of 3 months (mild to moderate asthma) or 4 weeks (severe asthma).
Further Inclusion criteria apply.
Exclusion criteria:
Significant conditions or medical conditions that could influence the results of the study or the patient's ability to participate in the study Malignancy requiring resection, radiation or chemotherapy within 5 years prior to screening Planned surgery during the trial Blood donation of more than 400ml within 4 weeks of starting trial or during the trial Subjects unable or unwilling to comply with the medication, lifestyle or dietary requirements of the trial Pregnant or nursing women History of cystic fibrosis Clinically significant bronchiectasis Acute or chronic infections including hepatitis, HIV and tuberculosis Thoracotomy with pulmonary resection Current significant alcohol or drug abuse Inability to produce sputum samples of sufficient quality Subjects with a sputum neutrophil count greater than 10 million cells per ml Subjects who have taken an investigational drug within 3 months or 6 half-lives of the therapeutic intervention prior to Visit 1
Additional exclusion criteria for asthma patients:
Respiratory tract infection or asthma exacerbation in the 6 week period prior to Visit 1 (patients with mild to moderate asthma should be exacerbation free for a period of 12 months prior to Visit 1.
Patients with documented non-compliance to prescribed asthma controller therapy Treatment with biological agents (other than Xolair for severe asthma) within four months prior to Visit 1 Patients who have completed a pulmonary rehabilitation program in the six weeks prior to Visit 1 or who are currently in a pulmonary rehabilitation program
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Asthma and healthy subject
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 352.2087.44001 Boehringer Ingelheim Investigational Site | Leicester | United Kingdom | ||||
| 352.2087.44004 Boehringer Ingelheim Investigational Site |
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This is a non-interventional, prospective, exploratory study. Asthma severity (mild, moderate or severe) was determined on the basis of medication use, spirometry (Forced Expiratory Volume in one second (FEV1) predicted values) and exacerbation history.
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Volunteers | This group consisted of all healthy volunteers aged between 18 and 70 years without any significant comorbid condition. |
| FG001 | Mild Asthma | Patients with asthma are categorized as mild if they are taking Short-acting beta-agonist (SABA) or SABA/Short-acting muscarinic-antagonist (SAMA) per re nata (as required) (PRN), have no exacerbation in previous 12 months and have FEV1 ≥80 % of predicted. |
| FG002 | Moderate Asthma | Patients with asthma are categorized as moderate if they are taking at least low dose Inhaled corticosteroid (iCS) ± 2nd controller, have no exacerbation in previous 12 months and have FEV1 ≥ 60 - ≤ 85 % of predicted. |
| FG003 | Severe Asthma | Patients with asthma are categorized as severe if they are taking at least medium dose iCS ± 2nd controller and have at least 1 exacerbation (requiring treatment with systemic corticosteroids) in previous 12 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Observed Subjects Set (OBS): All subjects enrolled in the trial, following the receipt of informed consent, who are eligible to enter the observation period.
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Volunteers | This group consisted of all healthy volunteers aged between 18 and 70 years without any significant comorbid condition. |
| BG001 | Mild Asthma | Patients with asthma are categorized as mild if they are taking Short-acting beta-agonist (SABA) or SABA/Short-acting muscarinic-antagonist (SAMA) per re nata (as required) (PRN), have no exacerbation in previous 12 months and have FEV1 ≥80 % of predicted. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Baseline (Visit 1) | Level of Tumour Necrosis Factor-alpha (TNF-α) [picograms per milliliter (pg/mL)] in blood at baseline (Visit 1) is presented. | Biomarker Subjects Set (BM) - All subjects, from the OBS [subjects enrolled in the trial, following the receipt of informed consent, and are eligible to enter the observation period], with at least one valid biomarker measurement either from blood or sputum at either visit. | Posted | Mean | Standard Deviation | pg/mL | Baseline (Visit 1) |
|
From baseline assessment (visit 1) till follow-up assessment (visit 2); up to 31 days
Observed Subjects Set (OBS): All subjects enrolled in the trial, following the receipt of informed consent, who are eligible to enter the observation period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Volunteers | This group consisted of all healthy volunteers aged between 18 and 70 years without any significant comorbid condition. |
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The study is considered exploratory in nature as the definitive power needed to assess yet unknown endotypes cannot be prospectively specified. The study is, however, adequately designed as hypothesis generating study informing interventional studies
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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Blood and sputum
Level of Interleukin-6 (IL-6) (pg/mL) in blood at follow-up visit 28 days after baseline (Visit 2) is presented. |
| follow-up visit 28 days after baseline (Visit 2) |
| London |
| United Kingdom |
| 352.2087.44002 Boehringer Ingelheim Investigational Site | Manchester | United Kingdom |
| 352.2087.44003 Boehringer Ingelheim Investigational Site | Southampton | United Kingdom |
| Withdrawal by Subject |
|
| BG002 | Moderate Asthma | Patients with asthma are categorized as moderate if they are taking at least low dose Inhaled corticosteroid (iCS) ± 2nd controller, have no exacerbation in previous 12 months and have FEV1 ≥ 60 - ≤ 85 % of predicted. |
| BG003 | Severe Asthma | Patients with asthma are categorized as severe if they are taking at least medium dose iCS ± 2nd controller and have at least 1 exacerbation (requiring treatment with systemic corticosteroids) in previous 12 months. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Patients with asthma are categorized as mild if they are taking Short-acting beta-agonist (SABA) or SABA/Short-acting muscarinic-antagonist (SAMA) per re nata (as required) (PRN), have no exacerbation in previous 12 months and have FEV1 ≥80 % of predicted. |
| OG002 | Moderate Asthma | Patients with asthma are categorized as moderate if they are taking at least low dose Inhaled corticosteroid (iCS) ± 2nd controller, have no exacerbation in previous 12 months and have FEV1 ≥ 60 - ≤ 85 % of predicted. |
| OG003 | Severe Asthma | Patients with asthma are categorized as severe if they are taking at least medium dose iCS ± 2nd controller and have at least 1 exacerbation (requiring treatment with systemic corticosteroids) in previous 12 months. |
|
|
| Primary | Level of Interleukin-6 (IL-6) in Blood at Baseline (Visit 1) | Level of Interleukin-6 (IL-6) (pg/mL) in blood at baseline (Visit 1) is presented. | Biomarker Subjects Set (BM) - All subjects, from the OBS [subjects enrolled in the trial, following the receipt of informed consent, and are eligible to enter the observation period], with at least one valid biomarker measurement either from blood or sputum at either visit. | Posted | Mean | Standard Deviation | pg/mL | Baseline (Visit 1) |
|
|
|
| Secondary | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | Level of Tumour Necrosis Factor-alpha (TNF-α) (pg/mL) in blood at follow-up visit 28 days after baseline (Visit 2) is presented. | Biomarker Subjects Set (BM) - All subjects, from the OBS [subjects enrolled in the trial, following the receipt of informed consent, and are eligible to enter the observation period], with at least one valid biomarker measurement either from blood or sputum at either visit. | Posted | Mean | Standard Deviation | pg/mL | follow-up visit 28 days after baseline (Visit 2) |
|
|
|
| Secondary | Level of Interleukin-6 (IL-6) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | Level of Interleukin-6 (IL-6) (pg/mL) in blood at follow-up visit 28 days after baseline (Visit 2) is presented. | Biomarker Subjects Set (BM) - All subjects, from the OBS [subjects enrolled in the trial, following the receipt of informed consent, and are eligible to enter the observation period], with at least one valid biomarker measurement either from blood or sputum at either visit. | Posted | Mean | Standard Deviation | pg/mL | follow-up visit 28 days after baseline (Visit 2) |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Mild Asthma | Patients with asthma are categorized as mild if they are taking Short-acting beta-agonist (SABA) or SABA/Short-acting muscarinic-antagonist (SAMA) per re nata (as required) (PRN), have no exacerbation in previous 12 months and have FEV1 ≥80 % of predicted. | 0 | 12 | 0 | 12 |
| EG002 | Moderate Asthma | Patients with asthma are categorized as moderate if they are taking at least low dose Inhaled corticosteroid (iCS) ± 2nd controller, have no exacerbation in previous 12 months and have FEV1 ≥ 60 - ≤ 85 % of predicted. | 0 | 20 | 0 | 20 |
| EG003 | Severe Asthma | Patients with asthma are categorized as severe if they are taking at least medium dose iCS ± 2nd controller and have at least 1 exacerbation (requiring treatment with systemic corticosteroids) in previous 12 months. | 0 | 27 | 0 | 27 |
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |