Tezepelumab (anti-TSLP-mab) in interstitial lung disease with progressive pulmonary fibrosis and elevated blood eosinophil granulocyte counts

Phase 1

• Conditions: Progressive pulmonary fibrosis interstitial lung disease with evidence of eosinophilia; MedDRA version: 21.1Level: PTClassification code 10021240Term: Idiopathic pulmonary fibrosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 21.1Level: LLTClassification code 10022619Term: Interstitial pulmonary fibrosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2022-003584-18-DE
• Lead Sponsor: Philipps University Marburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-01-27
• Last Update Posted: 15 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

1. Signed written informed consent
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 (Note: Progressive-fibrotic behavior before the initiation of antifibrotic therapy can be established by the local principal investigator and must include at least a decline in FVC of >5% or DLCO decline of >10% within in the last 12 24 months with worsening of respiratory symptoms unexplained by current infection or exacerbation of morbidities (Tzilas et al. Lancet Resp Med 2022). CT morphological evidence of progression is not mandatory, but increasing extent of fibrotic changes on CT with worsening of respiratory symptoms indicated progressive-fibrotic behavior. )
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)*
*combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
o oral
o intravaginal
o transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation:
o oral
o injectable
o implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system ( IUS)
• bilateral tubal occlusion
• vasectomised partner
• sexual abstinence

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 19

Exclusion Criteria

1. Oral corticosteroid dose >10mg/d
2. anti-IL5-(Receptor), anti IL4 or anti-IL13 biological therapy within the past 3 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 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the efficacy of Tezepelumab to decrease peripheral blood eosinophilia when compared to placebo after 24 weeks in progressive pulmonary fibrosis.<br><br>;Secondary Objective: To assess the effect of 210 mg Tezepelumab subcutaneous injection every 4 weeks on pulmonary function compared with placebo.<br><br>To assess the effect of 210 mg of Tezepelumab subcutaneous injection every 4 weeks on pulmonary fibrosis symptoms compared with placebo.<br><br>;Primary end point(s): Primary endpoint: Change in blood cell count (absolute numbers) after 24 weeks<br>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.<br>;Timepoint(s) of evaluation of this end point: After 24 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Key Secondary endpoints: <br>change from baseline in forced vital capacity (FVC) Key outcome measure: Mean difference vs placebo at Week 24 <br><br>Change from baseline in King’s Brief Interstitial Lung disease Questionnaire (K-BILD) or Quality of life in patients with idiopathic pulmonary fibrosis (QPF) after 24 weeks<br>Key outcome measure: Mean difference vs placebo at Week 24<br>;Timepoint(s) of evaluation of this end point: After 24 weeks