Asthma
Conditions
Brief summary
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.
Detailed description
Purpose:
Interventions
PROCEDUREBiofluid sampling
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Baseline (Visit 1) | Baseline (Visit 1) | Level of Tumour Necrosis Factor-alpha (TNF-α) \[picograms per milliliter (pg/mL)\] in blood at baseline (Visit 1) is presented. |
| Level of Interleukin-6 (IL-6) in Blood at Baseline (Visit 1) | Baseline (Visit 1) | Level of Interleukin-6 (IL-6) (pg/mL) in blood at baseline (Visit 1) is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 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. |
| Level of Interleukin-6 (IL-6) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers This group consisted of all healthy volunteers aged between 18 and 70 years without any significant comorbid condition. | 10 |
| 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. | 12 |
| 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. | 20 |
| 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. | 27 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Mild Asthma | Moderate Asthma | Severe Asthma | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.3 Years STANDARD_DEVIATION 14.6 | 36.1 Years STANDARD_DEVIATION 13.5 | 44.9 Years STANDARD_DEVIATION 12.6 | 50.2 Years STANDARD_DEVIATION 13.6 | 44.8 Years STANDARD_DEVIATION 14.2 |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 8 Participants | 16 Participants | 34 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants | 11 Participants | 35 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 | 0 / 10 | 0 / 12 | 0 / 20 | 0 / 27 |
| serious Total, serious adverse events | 0 / 10 | 0 / 12 | 0 / 20 | 0 / 27 |
Outcome results
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.
Time frame: Baseline (Visit 1)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Level of Interleukin-6 (IL-6) in Blood at Baseline (Visit 1) | 71.3 pg/mL | Standard Deviation 109 |
| Mild Asthma | Level of Interleukin-6 (IL-6) in Blood at Baseline (Visit 1) | 65.2 pg/mL | Standard Deviation 88.2 |
| Moderate Asthma | Level of Interleukin-6 (IL-6) in Blood at Baseline (Visit 1) | 245.0 pg/mL | Standard Deviation 426.3 |
| Severe Asthma | Level of Interleukin-6 (IL-6) in Blood at Baseline (Visit 1) | 133.9 pg/mL | Standard Deviation 639.5 |
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.
Time frame: Baseline (Visit 1)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Baseline (Visit 1) | 5.3 pg/mL | Standard Deviation 5.1 |
| Mild Asthma | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Baseline (Visit 1) | 9.3 pg/mL | Standard Deviation 23.4 |
| Moderate Asthma | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Baseline (Visit 1) | 10.6 pg/mL | Standard Deviation 13.1 |
| Severe Asthma | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Baseline (Visit 1) | 15.7 pg/mL | Standard Deviation 70.2 |
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.
Time frame: follow-up visit 28 days after baseline (Visit 2)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Level of Interleukin-6 (IL-6) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 47.7 pg/mL | Standard Deviation 59.7 |
| Mild Asthma | Level of Interleukin-6 (IL-6) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 86.1 pg/mL | Standard Deviation 107.6 |
| Moderate Asthma | Level of Interleukin-6 (IL-6) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 105.1 pg/mL | Standard Deviation 94.1 |
| Severe Asthma | Level of Interleukin-6 (IL-6) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 37.4 pg/mL | Standard Deviation 113.8 |
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.
Time frame: follow-up visit 28 days after baseline (Visit 2)
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 5.8 pg/mL | Standard Deviation 9.6 |
| Mild Asthma | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 8.1 pg/mL | Standard Deviation 14.7 |
| Moderate Asthma | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 5.2 pg/mL | Standard Deviation 5.5 |
| Severe Asthma | Level of Tumour Necrosis Factor-alpha (TNF-α) in Blood at Follow-up Visit 28 Days After Baseline (Visit 2) | 16.4 pg/mL | Standard Deviation 65.6 |