Tezepelumab (Anti-TSLP-mab) in progressive pulmonary fibrosis interstitial lung disease with evidence of eosinophilia - A prospective two-armed, phase II clinical multicentre randomized, placebo-controlled (2:1), blinded with open-label extension trial (TEFIBEOS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Philipps-Universitaet Marburg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

9 Jun 2025 → ongoing

Decision date (initial)

2024-09-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca GmbH · German Center for Lung Research

External identifiers

EU CT number

2024-510884-51-00

EudraCT number

2022-003584-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine the efficacy of Tezepelumab to decrease peripheral blood eosinophilia when compared to placebo after 24 weeks in progressive
pulmonary fibrosis.

Secondary objectives 6

1. To assess the effect of 210 mg Tezepelumab SC Q4W on pulmonary function compared with placebo
2. To assess the effect of 210 mg of Tezepelumab SC Q4W on pulmonary fibrosis symptoms compared with placebo
3. To assess the effect of 210 mg of Tezepelumab SC Q4W on other endpoints associated with progressive pulmonary fibrosis
4. To assess the effect of 210 mg of Tezepelumab SC Q4W on other pulmonary fibrosis control metrics
5. To assess the effect of 210 mg of Tezepelumab SC Q4W on general health-related quality of life
6. To assess the effect of 210 mg of Tezepelumab SC Q4W on need to adapt immunomodulatory comedication in non- IPF patients

Conditions and MedDRA coding

Progressive pulmonary fibrosis interstitial lung disease with evidence of eosinophilia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed written informed consent form
2. Adult patients ≥ 18 years, female and male
3. Patients with a diagnosis of IPF or a diagnosis of progressive pulmonary fibrosis due to chronic, eosinophilic pneumonia with fibrotic phenotype, fibrotic hypersensitivity pneumonitis / exogen allergic alveolitis or CTD-associated ILD with progressive fibrotic behaviour or other progressive fibrotic Interstitial lung diseases
4. receiving antifibrotic therapy at a stable dose (either nintedanib or pirfenidone) for at least 2 months which was initiated due to a diagnosis of IPF or progressive pulmonary fibrotic behavior of non-IPF ILD at the discretion of the treating physician
5. In non-IPF patients receiving immunosuppressive medication, dose must be stable for at least 3 months (except for prednisolone, where a dose of ≤ 10mg/d for at least 4 weeks is allowed)
6. blood eosinophilia with an absolute count of ≥ 150/µL at screening and/or BAL eosinophilia of ≥10% within the last 12 months prior to screening
7. Willingness of women of childbearing potential (WOCBP) to use highly effective birth control methods from the date of consent through the post study follow up examination at week 56 (According to CTFG recommendation)
8. A negative result in pregnancy test and additional pregnancy testing prior to each administration of the IMP should be performed during the duration of the trial and at the post study follow up visit at week 56.
9. Non-sterilized males who are sexually active with a female partner of childbearing potential must use a condom plus spermicide from Day 1 through 12 weeks after receipt of the final dose of IP.

Exclusion criteria 15

1. Oral corticosteroid dose >10mg/d
2. anti-IL5-(Receptor), anti-IL4 or anti-IL13 biological therapy within the past 4 months
3. Omalizumab therapy
4. Rituximab therapy within the past 9 months
5. JAK-inhibitors within the past 4 weeks
6. Cyclophosphamide within the past 6 months
7. Current smoker or former smoker <24 weeks
8. Severe lung functional impairment according to the treating physician interfering substantial with participation in the trial
9. Known active malignancy or high clinical suspicion of malignant disease
10. Unstable cardiovascular disease
11. Subjects with untreated systemic helminth parasitic infections or recurrent or active current bacterial, viral or fungal infection (excluding fungal infections of the nails), for example but not limited to active hepatitis B and C, typical or atypical mycobacteriosis or herpes zoster infections.
12. Pregnant or breastfeeding women
13. Receipt of live attenuated vaccines 30 days prior to the date of randomization
14. Known history of sensitivity to any component of the IP formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation
15. Concurrent enrolment in another clinical study involving an IP.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint: Change in blood cell count (absolute numbers) after 24 weeks Primary outcome measure: Change in number of eosinophils in differential blood cell count (absolute numbers) between baseline and 24 weeks of treatment compared to placebo.

Secondary endpoints 17

1. change from baseline in forced vital capacity (FVC)
2. Change from baseline in King’s Brief Interstitial Lung Disease Questionnaire (K-BILD) or Quality of life in patients with idiopathic pulmonary fibrosis (QPF) Questionnaire at 20 weeks
3. Time to decrease of FVC > 5% from baseline
4. Time to decrease of DLCO > 10% from baseline
5. Time to first acute exacerbation of underlying interstitial lung disease
6. Time to first all-cause hospitalization
7. Time to all-cause mortality
8. Time to composite endpoint of disease progression (defined as decline of FVC ≥ 5% or DLCOcSB ≥ 10% from baseline or death from any cause)
9. Change from baseline in total lung capacity (TLC)
10. Change from baseline in DLCOcSB
11. Change from baseline in DLCOc/VA
12. Change from baseline in capillary pO2
13. Change form baseline in 6-minute walking test distance
14. Change from baseline in Quality of life in patients with idiopathic pulmonary fibrosis (QPF) Questionnaire score. Key outcome measure: difference placebo vs week 24.
15. Need to increase corticosteroid dose
16. Need to increase dose of disease-modifying antirheumatic drugs
17. Need to initiate new disease-modifying antiheumatic drugs

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Philipps-Universitaet Marburg

Sponsor organisation

Philipps-Universitaet Marburg

Address

Karl-Von-Frisch-Strasse 4

City

Marburg

Postcode

35043

Country

Germany

Scientific contact point

Organisation

Philipps-Universitaet Marburg

Contact name

Coordinating Investigator

Public contact point

Organisation

Philipps-Universitaet Marburg

Contact name

Project Management

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 13 files

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

Application history

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