1) To identify T2 low biomarkers and 2) to unravel the mechanisms and downstream effects of Tezepelumab in T2 low asthma.
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Outcomes of single cell sequencing
Secondary outcome
NA
Background summary
Approximately one third of asthma patients have a T2 low biomarker profile.
Patients with a T2 low profile, in particular patients with an obese phenotype,
benefit poorly from usual care (i.e. Inhaled Corticosteroids, GINA 2020).
Development of new drugs and biologicals are necessary to treat patients with
severe T2 low asthma. New drugs for this category of patients will hopefully
lead to better control of their asthma and thus lowering the number of
exacerbations and the burden of disease. However, developments in T2 low asthma
have progressed slowly, due to a poor understanding of T2 low pathways. The
recent finding of the possible roles of Thymic Stromal Lymphopoietin (TLSP) in
T2 low asthma may shed new light on an old theme. Recent trials suggest a
central role of TSLP, as anti-TSLP (Tezepelumab), reduced the exacerbation
frequency in patients with non-eosinophilic asthma. A clear understanding of
the cellular changes during treatment with anti-TSLP in relation to Asthma
severity will benefit future treatment regimens with Tezepelumab. Furthermore,
studying the differences between obese and non-obese patients is important as
these two T2 low phenotypes may have distinct cellular inflammatory patterns.
Study objective
1) To identify T2 low biomarkers and
2) to unravel the mechanisms and downstream effects of Tezepelumab in T2 low
asthma.
Study design
Explorative, prospective, open-label, intervention trial
Intervention
Every 4 weeks, for 20 weeks, the patient will receive 210 mg of Tezepelumab by
injection under the skin.
Study burden and risks
Tezepelumab decreases the exacerbation rate in patients with severe asthma
significantly, regardless of eosinophilia[1-4]. Most common adverse events
include bronchitis, nasopharyngitis and headaches. Approximately 9% of patients
treated with medium dose Tezepelumab developed at least 1 serious event. No
treatment related deaths were reported in earlier trials.
Kleiweg 500
Rotterdam 3045 PM
NL
Kleiweg 500
Rotterdam 3045 PM
NL
Listed location countries
Age
Inclusion criteria
- Age 18-75 years
- Written informed consent
- BMI >18 with weight >40kg at inclusion
- Documented physician-diagnosed asthma for at least 12 months prior to
inclusion (12% reversibility in FEV1 or positive histamine/methacholine
provocation test)
- Controller regime with medium- or high dosed ICS
* Medium: >=250µg and <500µg fluticasone daily
* High: >=500µg fluticasone daily
* Or bio-equivalent dose of other type of ICS
- Stable dose of controller medication other than ICS/LABA (leukotriene
receptor inhibitors, theophylline, secondary ICS, LAMA, chromones)
- Pre-BD FEV1 value of >= 40%
- ACQ >= 1.5
- T2 low profile:
* Peripheral blood eosinophils < 150 cells/µL
* FeNO < 20 ppb
* No clinically proven allergen driven asthma
* No need for maintenance OCS
- >=2 exacerbation events or >=1 exacerbation with hospitalization in the 12
months prior to inclusion
* Exacerbation: burst of OCS for at least 3 days
- Reproduction:
* Females of childbearing potential who are sexually active with a
nonsterilized male partner must use a highly effective method of contraception
from screening, and must agree to continue using such precautions for 16 weeks
after the final dose of Tezepelumab.
Exclusion criteria
- Current smokers
- Stopped smoking <6 months prior to inclusion but >= 10 pack years
- Use of immune modulatory drugs, Azithromycin, Montelukast and Theophylline
- Concurrent or intercurrent disease that may compromise safety of the patient
or may compromise the ability to participate in the trial
- Concomitant respiratory disease that will interfere with the evaluation of
the product or the interpretation of the results
- Evidence of active liver disease
- History of cancer
- Acute upper or lower respiratory infections requiring antibiotics or
antiviral medications within 15 days prior to first visit
- Pregnant, breastfeeding or lactating females
- Unwillingness or inability to follow the procedures outlined in the protocol
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2021-004877-29-NL |
| CCMO | NL78940.100.21 |
| Other | NL9768 |