The primary objective of the study is as follows:· To compare the rate of asthma exacerbations between patients with low baseline periostin levels (< 50 ng/mL) and patients with high baseline periostin levels (* 50 ng/mL), as measured by central…
ID
Source
Brief title
Arietta
Condition
- Upper respiratory tract disorders (excl infections)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The outcome measures for this study are:
· Asthma exacerbation defined as:
- For patients who are not on maintenance oral corticosteroid therapy: new or
increased asthma symptoms (including wheeze, cough, dyspnoea, chest tightness,
and/or nocturnal awakening due to these symptoms) that lead to treatment with
systemic corticosteroids or to hospitalization. Treatment with systemic
corticosteroids is defined as treatment with oral, intravenous (IV), or
intramuscular (IM) corticosteroids for * 3 days or an emergency department
visit with at least one dose of IV or IM corticosteroids.
- For patients who are on maintenance oral corticosteroid therapy: new or
increased asthma symptoms (including wheeze, cough, dyspnoea, chest tightness,
and/or nocturnal awakening due to these symptoms) that lead to intensified
treatment with systemic corticosteroids, defined as * 30 mg or 0.5 mg/kg for *
3 consecutive days, or to hospitalization.
- Note: hospitalization and systemic corticosteroid treatment criteria must be
verified in medical records from the treating institution.
Additional details are provided in Appendix 2.
· Pre-bronchodilator FEV1
· Time to first asthma exacerbation during the course of the study
· TTF where treatment failure is defined as the first occurrence of one of the
following events during the course of the study:
- Asthma exacerbation
- Clinically meaningful change in SoC asthma treatment as reported by the
Investigator and confirmed by the SC
· Asthma-specific health-related quality of life as assessed by MiniAQLQ
overall score
· Asthma-specific symptom scores, as assessed by the ACQ-7 and the ACT
· SoC treatments (relevant treatments, treatment characteristics, and changes
in these considered clinically meaningful by the Investigator with confirmation
from the SC)
· Asthma-related health care utilization defined by hospitalizations, emergency
department visits, and acute care visits due to asthma and asthma-related
symptoms
- Serum periostin level as assessed by both central study laboratory testing
and by regional reference laboratory testing (regional reference laboratories
conducting periostin testing are expected to be established in select regions
later in the course of the study - see Section 4.3.9.2.1)
· FeNO
· Blood eosinophil level as assessed by both local and central study laboratory
testing
· Serum IgE level as assessed by both local and central study laboratory
testing
Secondary outcome
The safety outcome measures for this study are the nature, frequency and
severity of the following:
· Study assessment-related AEs
· SAEs: defined as any event that is fatal or life-threatening, results in
unplanned hospitalization or prolongs an existing hospitalization, results in
congenital anomaly/birth defect, or is deemed medically significant by the
Investigator
· Medical events of special interest: defined as malignancies (e.g. lymphoma);
infections including respiratory infections, parasitic infections such as
helminthic (e.g. schistosoma infections) and protozoan (e.g. Giardia lamblia),
opportunistic infections such as histoplasmosis and coccidioidomycosis, and
Listeria monocytogenes infection; newly diagnosed diabetes mellitus; cataracts;
bone fractures; dental operations; anaphylaxis, anaphylactoid and
hypersensitivity events; and pregnancies
Exploratory Outcome Measures
The exploratory outcome measures for this study are as follows:
· Work and activity impairment as assessed by the WPAI-Asthma
· Asthma symptoms as measured by the ASUI
Background summary
Asthma is one of the most common chronic diseases in the world. It is
characterized by chronic airway inflammation, bronchial hyper-responsiveness,
mucus hyper-secretion and reversible airflow obstruction that result in
recurrent attacks of breathlessness, chest tightness, cough and wheezing.
The relevance of molecular biomarkers as both research and clinical tools in
asthma has risen with the characterization of the pathophysiological
mechanisms.
Clinically amenable biomarkers of these disease processes are needed to fully
exploit the potential for improvements in accurate asthma subtype diagnoses,
treatment selection and monitoring of disease progress and treatment response.
Among multiple candidates, periostin presents the potential to guide each of
these aspects of asthma management. Its relationship to asthma outcomes and
other Th2-driven disease biomarkers merits further study in a longitudinal
setting.
(see protocol page 16-18)
Study objective
The primary objective of the study is as follows:
· To compare the rate of asthma exacerbations between patients with low
baseline periostin levels (< 50 ng/mL) and patients with high baseline
periostin levels (* 50 ng/mL), as measured by central laboratory testing, in
order to evaluate periostin as a prognostic biomarker that can identify at-risk
asthmatics
The secondary objectives of the study are to assess the following:
· The prognostic value of baseline periostin levels with respect to:
- Change in pre-bronchodilator FEV1
- Time to first asthma exacerbation
- Change in FeNO
- Change in asthma-specific health-related quality of life as assessed by the
Mini Asthma Quality of Life Questionnaire (MiniAQLQ)
- Change in asthma-specific symptom scores, as assessed by the Asthma Control
Questionnaire-7 (ACQ-7) and the Asthma Control Test (ACT)
- Time to treatment failure (TTF)
· The prognostic value of baseline periostin levels, as measured by central
laboratory testing and as measured by regional reference laboratory testing,
with respect to rate of asthma exacerbations (regional reference laboratories
conducting periostin testing are expected to be established in select regions
later in the course of the study - see Section 4.3.9.2.1)
· The prognostic value of established risk factors measured at baseline (blood
eosinophil counts, FeNO, serum IgE and history of asthma exacerbations over the
12 months prior to Visit 1) with respect to the rate of asthma exacerbations
during the study
· The prognostic value of composite measures that include baseline periostin
and other established risk factors measured at baseline (i.e. blood eosinophil
count, FeNO, serum IgE, history of asthma exacerbations) with respect to the
rate of asthma exacerbations
· The prognostic value of baseline periostin levels in subgroups of patients
(e.g. treatment subgroups such as Global Initiative for Asthma [GINA] step 4
500-1000 *g fluticasone propionate [FP], GINA step 4 >1000 *g FP, GINA step 5;
geographical subgroups; or ethnic subgroups) with respect to the rate of asthma
exacerbations
· The association between baseline periostin levels and clinically meaningful
changes to standard of care (SoC) asthma treatment as reported by the
investigator and confirmed by the study Steering Committee (SC)
- The association between periostin and other biomarker levels measured at
baseline (FeNO, blood eosinophil count, serum IgE) and the rate of urgent
asthma-related health care utilization over the study period
· Intra- and inter-patient variation in periostin levels, blood eosinophil
counts, serum IgE levels and FeNO levels
· Variation between periostin levels, blood eosinophil counts and serum IgE
levels as measured by the central laboratory versus regional reference
(periostin) or local (blood eosinophils, IgE) laboratories
The safety objective of the study is to evaluate the nature, frequency and
severity of the following over the study period:
· Adverse events (AEs) related to study assessments (e.g. blood draws or
spirometry)
· Serious adverse events (SAEs)
· Medical events of special interest (MESIs)
The exploratory objectives for this study include, but are not limited to,
assessment of the following:
· Correlation between periostin levels and key asthma biomarkers (i.e. blood
eosinophil count, serum IgE, FeNO)
· Correlation of blood eosinophil count, FeNO, serum IgE and history of asthma
exacerbations with rate of asthma exacerbations, FEV1, time to first asthma
exacerbation, changes to SoC asthma treatment, asthma-related quality of life
(assessed by the MiniAQLQ), and asthma-related healthcare utilization
· Change in asthma control, as measured by the ACQ-7 score, with respect to
other biomarkers measured at baseline (i.e. FeNO, blood eosinophil count, serum
IgE)
· Change in work and activity impairment, as assessed by the Work Productivity
and Activity Impairment Questionnaire-Asthma (WPAI-Asthma), with respect to
periostin and other biomarkers measured at baseline (i.e. FeNO, blood
eosinophil count, serum IgE)
· Change in asthma symptoms, as measured by the Asthma Symptom Utility Index
(ASUI) with respect to periostin and other biomarkers measured at baseline
(i.e. FeNO, blood eosinophil count, serum IgE)
· Change in asthma symptoms, as measured by the Asthma Control Test (ACT) with
respect to other biomarkers measured at baseline (i.e. FeNO, blood eosinophil
count, serum IgE)
Study design
This is a prospective, single-arm, longitudinal, international, multicentre
study in a real-world cohort of adult severe asthma patients that is being
conducted to assess the relationships between asthma biomarkers and
asthma-related health-outcomes.
Study burden and risks
The study assessments consist of non-invasive methods commonly used in asthma
SoC (FEV1 and FeNO measurement) in addition to peripheral blood sampling and
clinically applicable patient questionnaires. To reduce the burden associated
with travel and time in the clinic, study evaluation days can occur within a
wide temporal window (± 28 days) to increase the likelihood of coinciding with
a clinic visit for standard care, and two of the five study visits will be
conducted by telephone.
Beneluxlaan 2a
Woerden 3446 GR
NL
Beneluxlaan 2a
Woerden 3446 GR
NL
Listed location countries
Age
Inclusion criteria
- Males and females ><=18 years of age
- Asthma diagnosed by a respiratory physician ><= 12 months prior to
study enrolment
- Pre-bronchodilator forced expiratory volume in 1 second (FEV1) of
30%-85% at baseline
- Documented bronchodilator response defined as ><=12% relative
improvement in FEV1 after bronchodilator administration OR a positive
methacholine bronchial challenge test with PC20 (provocative
concentration causing a 20% fall in FEV1) < 8 milligrams at study
baseline or within 24 months prior to baseline
- Current treatment with a total daily dose of ><=500 microgram of
fluticasone propionate administered by dry powder inhaler (or
equivalent) and at least one of the following controller medications:
long-acting beta-agonists (LABAs), leukotriene receptor antagonists
(LTRAs), long-acting muscarinic antagonists (LAMAs), theophylline or
oral corticosteroids; with a continued duration of at least three months
prior to baseline
Exclusion criteria
- Acute or chronic parasitic, bacterial, fungal or viral infections that
required, or currently require, hospitalization or antimicrobial treatment
during the last four weeks
- Acute asthma exacerbation event treated with increased doses of oral
or any dose of intramuscular or intravenous corticosteroids within six
weeks prior to baseline
- Other relevant pulmonary diseases (e.g. chronic obstructive
pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis,
pulmonary arterial hypertension, tuberculosis) requiring treatment
within 12 months prior to baseline
- Alcohol or substance abuse within 12 months prior to baseline
- Current smoker defined as having smoked at least one cigarette (or
pipe, cigar, or marijuana) per day for >=30 days within the three months
prior to baseline
- Ex-smokers with >=10 pack-year smoking history
- Treatment with omalizumab or any anti- interleukin (IL)-4, anti-IL-5,
or anti-IL-13 targeted therapy currently or within six months prior to
baseline
- Prior treatment with bronchial thermoplasty
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL54020.056.15 |