Effect of Tezepelumab on epithelial TSLP induction after viral mimic stimulation in severe asthma with and without chronic rhinosinusitis
- Trial ID
- 2026-527032-14-00
- Protocol
- BBH-LFOR-2026-01
- Sponsor
- Region Hovedstaden
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to compare epithelial TSLP protein induction following viral‑mimic stimulation in patients with severe asthma who have chronic rhinosinusitis versus those without, providing insight into the role of epithelial cytokine responses in disease heterogeneity.
Secondary objectives are to:
- Compare epithelial TSLP mRNA induction after viral‑mimic stimulation between patients with and without chronic rhinosinusitis.
- Assess bronchial mucosal eosinophil activation and mast cell phenotype before and after treatment with tezepelumab.
- Evaluate bronchial mucosal eosinophil activation and mast cell phenotype in severe asthma patients with versus without chronic rhinosinusitis.
Participants
The trial enrolled adult participants (≥18 years) of both sexes diagnosed with severe asthma, including individuals with and without chronic rhinosinusitis. The sponsor did not provide information on the total number of participants. Eligible subjects were identified from an outpatient recruitment pool based on a clinical decision to initiate tezepelumab therapy in accordance with licensing and guideline criteria, and from the 3TR‑ABC cohort at the Bispebjerg site who had completed a 1‑year follow‑up and were available for baseline nasal or bronchial epithelial cell sampling. Inclusion required the ability to provide written informed consent and compliance with study procedures. Both female and male patients were represented in the study population.
Plans and Procedures
The RHINOME study is a post‑authorisation Phase IV investigation evaluating the effect of subcutaneous tezepelumab (210 mg) on epithelial thymic stromal lymphopoietin (severe asthma) patients, with and without chronic rhinosinusitis, in routine clinical care. The trial enrolment commenced on 15 July 2026 and is scheduled to conclude on 1 August 2029, encompassing an overall participant involvement of up to three years. After obtaining written informed consent, eligible individuals undergo a screening visit to confirm diagnosis, eligibility criteria, and baseline bio‑sampling of nasal and/or bronchial epithelial cells. The baseline visit includes administration of the study medication, collection of epithelial cell cultures, and measurement of TSLP protein levels after poly(I:C) stimulation. Subsequent follow‑up visits are planned to monitor safety, collect additional bronchial mucosal biopsies, and assess secondary endpoints, with a key assessment occurring at visit 4. The study concludes with an end‑of‑study visit during which final samples are obtained and participants are discontinued from the investigational regimen. Participants may be withdrawn early for reasons such as withdrawal of consent, significant protocol deviations, or emergence of safety concerns that warrant discontinuation.
Treatment
The investigational product is Tezspire 210 mg solution for injection supplied in a pre‑filled pen or a pre‑filled syringe. Each dose contains the monoclonal antibody tezepelumab and is presented as a solution for injection. The medication is administered by subcutaneous injection at a dose of 210 mg, delivered according to the study‑specified dosing schedule.
No additional investigational agents, placebo, or active comparator are administered in this trial; participants receive only the study medication as described.
Efficacy
Efficacy will be evaluated using predefined biological endpoints. The primary endpoint is TSLP protein levels in nasal and bronchial epithelial cell culture supernatant measured 24 hours after poly(I:C) stimulation at the baseline visit, expressed as log₂ fold changes relative to unstimulated controls. Secondary endpoints include TSLP mRNA expression in the same cultured cells measured 3 hours after poly(I:C) stimulation at baseline (log₂ fold changes versus unstimulated controls), and the assessment of markers of eosinophilic activation and mast cell phenotypes in bronchial mucosal biopsies. For the tissue markers, changes from baseline to visit 4 will be quantified in major tissue compartments, and baseline values will be compared between participants with and without chronic rhinosinusitis.
Measurements will be performed at the baseline visit and at visit 4 according to the specified timepoints (3 hours and 24 hours post‑stimulation for epithelial cultures; biopsy collection at baseline and visit 4 for tissue markers). Collected samples will be processed to determine protein concentrations, mRNA levels, and immunohistochemical markers, and data will be analyzed by calculating log₂ fold changes and by comparing group differences and longitudinal changes using appropriate statistical methods.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Outpatient recruitment pool: 1. Diagnosed with severe asthma.
- Outpatient recruitment pool: 2. Adult ≥18 years.
- Outpatient recruitment pool: 3. Clinical decision to initiate tezepelumab for severe asthma after meeting licensing, local and national guidelines.
- Outpatient recruitment pool: 4. Able to give valid written informed consent, and compliant with study procedures and study visits.
- 3TR-ABC recruitment pool: 1. 3TR-ABC participant at the Bispebjerg site who completed 1-year follow-up visit.
- 3TR-ABC recruitment pool: 2. Specific bio-sampling for nasal and/or bronchial epithelial cells (NECs and/or BECs) at bio-naïve baseline.
- 3TR-ABC recruitment pool: 3. Able to give valid written informed consent.
Exclusion Criteria
- Outpatient recruitment pool: 1. Known hypersensitivity to the active substance or any excipient in tezepelumab.
- Outpatient recruitment pool: 2. Participation in an interventional clinical trial within 3 months of the baseline visit, or receipt of any investigational medicinal product within 3 months or 5 half-lives, whichever is longer.
- Outpatient recruitment pool: 3. Participation in other studies that, in the investigator's view, will impact the study outcomes.
- Outpatient recruitment pool: 4. Other clinically significant medical disease or uncontrolled concomitant disease likely, in the investigator's opinion, to require a change in therapy or to impair the ability to participate.
- Outpatient recruitment pool: 5. Unwilling or unable, in the investigator's opinion, to participate in study procedures and assessments.
- 3TR-ABC recruitment pool: 1. Known quality issues with airway samples making them insufficient for planned key analyses.
- 3TR-ABC recruitment pool: 2. Any participant who has specifically withdrawn their consent for future use of samples in the 3TR-ABC study.
- Outpatient recruitment pool: 6. Known or suspected pregnancy or breastfeeding, at the baseline (screening) visit. In individuals of childbearing potential, pregnancy is ruled out by a negative urine pregnancy test before inclusion.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Not Yet Recruiting | 15 Jul 2026 | 72 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Tezspire 210 mg solution for injection in pre-filled pen | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS INJECTION | 210 | 13 | PRD10257836 |
Tezspire 210 mg solution for injection in pre-filled syringe | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE (INJECTION) | SUBCUTANEOUS USE | 210 | 13 | PRD9947970 |