DIRECTION Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Decision date (initial)

2026-03-22

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate that Tezepelumab and Dupilumab lead to a clinical meaningful improvement of nasal polyp disease as defined by a minimal reduction of nasal polyp score (NPS) by 1 point or a reduction in sino-nasal outcome test (SNOT)-22 by 8.9 points between baseline and 12 months.

Secondary objectives 1

1. To evaluate the effect of Tezepelumab and Dupilumab between baseline and 1 year on: o Olfactory perception (as measured by Sniffin’Sticks Identification Test (SSIT)-16) o Forced Expiratory Volume (FEV)1 % (as measured by portable spirometer if feasible) o Peak nasal inspiratory flow (PNIF) (as measured by PNIF-meter) o Perception of asthma control (as determined by asthma control test (ACT) and asthma quality of life questionnaire (AQLQ)), o Perception of chronic rhinosinusitis (CRS) symptoms (visual analogue scale (VAS) score) o Perception of allergic symptoms (VAS score) o Perception of sense of smell (VAS score) o Exploratory in selected centers:  Nasal and blood biomarkers (mediators, total IgE, allergen-specific IgE, …)  Transcriptomics  Microbiome composition and diversity o Safety and tolerability

Conditions and MedDRA coding

Chronic Rhinosinusitis with Nasal Polyps

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. >18 years
2. Willingness to participate in the study
3. Suffer from uncontrolled CRSwNP according to EPOS criteria
4. Indication for biologic treatment in the opinion of the investigator and according to the reimbursement criteria established by the Austrian Federation of Social Insurances

Exclusion criteria 10

1. Pregnancy (as determined by beta human chorionic gonadotropin (β-HCG) test)
2. Patients receiving ongoing or having received biological therapy in the last 3 months for type-2 diseases like asthma, atopic dermatitis, chronic obstructive pulmonary disease (COPD), urticaria and eosinophilic esophagitis
3. Patients who intend to achieve pregnancy within the study period
4. Systemic corticosteroid treatment within the last three months
5. Hypersensitivity to the active substance or any of the excipients in the two IMPs
6. Participation in another investigational drug trial antibodies for asthma, CRSwNP, atopic dermatitis or allergic rhinitis
7. Breastfeeding patients
8. Patients with severe anatomic variations or deviations that do not allow access to all areas in the nasal cavity
9. Patients with permanent immunosuppression
10. A mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in NPS score (0-8 points) or the change in SNOT-22 (Scale of 0-110) from baseline to 12 months.

Secondary endpoints 12

1. Percentage of patients with good-excellent (4-5 criteria), poor-moderate (1-3 criteria) and no response (0 criteria) according to EPOS/EUROFREA criteria during one year of therapy with Dupilumab or Tezepelumab
2. Change in in QoL parameters (e.g., SNOT-22 score and subcategories, scale 0-110, EQ-5D-3L, scale: 5-15) and clinical parameters (e.g. NPS, scale: 0-8; ECP, 0-200µg/L) during one year of therapy with Dupilumab or Tezepelumab
3. Change in objective (Sniffin’sticks, 0-16 points) and subjective (VAS for olfactory performance (0-10cm), SNOT 22 items) during one year of therapy with Dupilumab or Tezepelumab
4. change in peak nasal inspiratory flow (PNIF, 0-370 L/min) or FEV 1 (spirometer, 0-ca.120%(young patients)) during one year of therapy with Dupilumab or Tezepelumab
5. change in perception of asthma control (ACT 0-25 Points or AQLQ 0-105 points) during one year of therapy with Dupilumab or Tezepelumab
6. change in perception of CRS symptoms (VAS, 0-10 cm) during one year of therapy with Dupilumab or Tezepelumab
7. occurrence of side effect as determined by diary or patients oral report during one year of therapy with Dupilumab or Tezepelumab, change in routine blood parameters
8. Change in allergic symptoms (TRSS 0-21 points, questionnaire) and allergic sensitization (skin prick test, number of sensitizations) during one year of treatment with Dupilumab or Tezepelumab
9. Change in diversity (Chao1 and Shannon Index, 0-open) and abundance (0-open) of the nasal microbiome during one year of treatment with Dupilumab or Tezepelumab
10. Change in relative levels of mediators (Normalized Protein Expression=NPX, 0-open) as determined by OLINK during one year of treatment with Dupilumab or Tezepelumab
11. Change in relative gene expression (Δ Cycle threshold (Ct): Difference between Ct of the target gene and a reference gene, 0-open) of oxidative stress response induced genes during one year of treatment with Dupilumab or Tezepelumab
12. Change in allergic sensitization (allergen-specific IgE levels, kUA/L) in nasal secretions and serum during one year of treatment with Dupilumab or Tezepelumab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Ear, Nose and Throat Disease

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Ear, Nose and Throat Disease

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications