Strona Badania kliniczne Nct

Summary
EudraCT Number:2022-003584-18
Sponsor's Protocol Code Number:KKS-307
National Competent Authority:Germany - PEI
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2023-01-27
Trial results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedGermany - PEI
A.2EudraCT number2022-003584-18
A.3Full title of the trial
Tezepelumab (Anti-TSLP-mab) in progressive pulmonary fibrosis interstitial lung disease with evidence of eosinophilia
Tezepelumab (Anti-TSLP-mab) bei progressiver interstitieller Lungenfibrose mit Nachweis von Eosinophilie
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Tezepelumab (anti-TSLP-mab) in interstitial lung disease with progressive pulmonary fibrosis and elevated blood eosinophil granulocyte counts
Tezepelumab (Anti-TSLP-mab) bei interstitieller Lungenerkrankung mit fortschreitender Lungenfibrose und einer erhöhten Anzahl von eosinophilen Granulozyten im Blut
A.4.1Sponsor's protocol code numberKKS-307
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorPhilipps University Marburg
B.1.3.4CountryGermany
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportGerman Center of lung reserch
B.4.2CountryGermany
B.4.1Name of organisation providing supportAstraZeneca
B.4.2CountryGermany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationKoordinierungszentrum für Klinische Studien (KKS) Marburg
B.5.2Functional name of contact pointSandra Soehler
B.5.3 Address:
B.5.3.1Street AddressKarl-von-Frisch-Straße 4
B.5.3.2Town/ cityMarburg
B.5.3.3Post code35043
B.5.3.4CountryGermany
B.5.4Telephone number+4964212826618
B.5.6E-mailtefibeos@kks.uni-marburg.de
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Tezspire
D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameTezspire
D.3.4Pharmaceutical form Solution for injection in vial
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMP
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product Yes
D.3.11.13.1Other medicinal product typemonoclonal antibody
D.8 Information on Placebo
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboSuspension for injection
D.8.4Route of administration of the placeboSubcutaneous use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Progressive pulmonary fibrosis interstitial lung disease with evidence of eosinophilia
E.1.1.1Medical condition in easily understood language
Progressive pulmonary fibrosis interstitial lung disease with evidence of eosinophilia
E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level PT
E.1.2Classification code 10021240
E.1.2Term Idiopathic pulmonary fibrosis
E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level LLT
E.1.2Classification code 10022619
E.1.2Term Interstitial pulmonary fibrosis
E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To determine the efficacy of Tezepelumab to decrease peripheral blood eosinophilia when compared to placebo after 24 weeks in progressive pulmonary fibrosis.
E.2.2Secondary objectives of the trial
To assess the effect of 210 mg Tezepelumab subcutaneous injection every 4 weeks on pulmonary function compared with placebo.

To assess the effect of 210 mg of Tezepelumab subcutaneous injection every 4 weeks on pulmonary fibrosis symptoms compared with placebo.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Signed written informed consent
2. Adult patients ≥ 18 years, female and male
3. Patients with a diagnosis of IPF, chronic, fibrotic eosinophilic pneumonia or CTD-associated ILD with progressive-fibrotic disease behaviour (Note: Progressive-fibrotic behavior 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 months with worsening of respiratoy symptoms unexplained by current infection or excacerbation of morbidities (Tzilas et al. Lancet Resp Med 2022). CT morphological evidence of progression is not mandatory. )
4. receiving antifibrotic therapy at a stable dose (either nintedanib or pirfenidone) for at least 3 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 blood eosinophilia with an absolute count of ≥ 150/µL at screening or BAL eosinophilia of ≥10% within the last 12 months prior to screening

6. 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

7. 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

8. 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.
E.4Principal exclusion criteria
1. Oral corticosteroid dose >10mg/d
2. anti-IL5-(Receptor), anti IL4 or anti-IL13 biological therapy
3. Omalizumab therapy
4. Rituximab therapy
5. JAK-inhibitors
6. Cyclophosphamide
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.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.Contraindications against treatment with Tezepelumab or known hypersensitivity, intolerance or allergy against any component of the IMP
13.Pregnant or breastfeeding women
14.Receipt of live attenuated vaccines 30 days prior to the date of randomization
15.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
16.Concurrent enrolment in another clinical study involving an IP.
E.5 End points
E.5.1Primary end point(s)
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.
E.5.1.1Timepoint(s) of evaluation of this end point
After 24 weeks
E.5.2Secondary end point(s)
Key Secondary endpoints:
change from baseline in forced vital capacity (FVC) Key outcome measure: Mean difference vs placebo at Week 24

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
Key outcome measure: Mean difference vs placebo at Week 24
E.5.2.1Timepoint(s) of evaluation of this end point
After 24 weeks
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Quality of Life
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) Yes
E.7.3Therapeutic confirmatory (Phase III) No
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned6
E.8.5The trial involves multiple Member States No
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA No
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.7Trial has a data monitoring committee No
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
End of study for the blinded phase is defined as “Last Patient Last Visit” (week 24).

End of study for the unblinded phase is defined as “Last Patient Last Visit” and data base closure including the post study follow up phase of 12 weeks in which all patients receive SOC treatment including antifibrotic medication and which ends with the last visit at week 56.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 20
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 19
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state39
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
After the end of the study (either 44 weeks of tezepelumab or 20 weeks of placebo followed by 20 weeks of tezepelumab), Tezepelumab will be discontinued and SOC medication will be continued including antifbrotic medication.
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-05-19
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-06-26
P. End of Trial
P.End of Trial StatusOngoing

Sponsorzy i współpracownicy

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