Double-blinded (treatment group unknown to physician and patient), randomised (treatment group allocated by chance) phase II trial on the efficacy and tolerability of an 8 week treatment with two different doses of budesonide tablets dissolving in the mouth compared to placebo (medication without active substance), for prevention of constrictions of the oesophagus in adult patients after removal of cancer tissue using an endoscopic surgery technique

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dr. Falk Pharma GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

12 May 2020 → 31 Mar 2026

Decision date (initial)

2024-11-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507897-42-00

EudraCT number

2018-002617-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Prophylaxis

To assess the efficacy of eight weeks treatment with 2 x 1 mg/day or 2 x 2 mg/day budesonide orodispersible tablets vs. placebo for prevention of oesophageal strictures after endoscopic submucosal dissection

Secondary objectives 2

1. To study safety and tolerability of budesonide orodispersible tablets vs. placebo by means of adverse events and laboratory parameters
2. To assess patients' quality of life

Conditions and MedDRA coding

Prevention of oesophageal strictures in adult patients after endoscopic submucosal dissection

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent
2. Male or female patients, 18 to 85 years of age
3. Estimated life expectancy of at least one year (not applicable in Portugal);
4. ECOG Performance Status of ≤ 2 at the randomisation visit (i.e. after the ESD-procedure);
5. a) Biopsy proven or endoscopically suspect oesophageal SCC and/or high grade dysplasia in a focal lesion of the squamous epithelium, treated with ESD; or b) Biopsy proven or endoscopically suspect BE-HGD or EAC, treated with ESD
6. Mucosal defect after ESD of a) ≥ 50% oesophageal circumference in a patient with SCC, or b) ≥ 75% oesophageal circumference in a patient with BE-HGD or EAC
7. Negative pregnancy test in females of childbearing potential at the screening visit;
8. Women of childbearing potential agree to apply during the entire duration of the trial an effective method of birth control, which is defined as those, which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly. Such methods include implants, injectables, combined oral contraceptive method, combined contraceptive patches and vaginal rings, copper containing IUDs, sexual abstinence, or vasectomised partner. The investigator is responsible for determining whether the patient applies adequate birth control methods to allow for trial participation. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or post-menopausal with at least two years without spontaneous menses.

Exclusion criteria 26

1. Any prior or intended chemotherapy for oesophageal cancer;
2. Any prior ESD in the area where ESD will be done;
3. Any prior or intended oesophageal surgery or surgery for the mediastinum, endoscopic mucosal resection (EMR), or radio frequency ablation (RFA), in the area where ESD will be done;
4. Evidence of regional lymph node metastases or distant metastases prior to ESD;
5. Any prior or intended radiotherapy which involves or affects the area of ESD during the last 5 yea
6. Any prior endoscopic dilation for oesophageal stenosis which involves or affects the area of ESD during the last 5 years;
7. Any other concomitant oesophageal disease (e.g. eosinophilic oesophagitis, oropharyngeal or oesophageal bacterial, viral, or untreated or inadequately treated fungal infection, inadequately treated candida oesophagitis or Zenker’s diverticulum);
8. Achalasia, scleroderma oesophagus, or systemic sclerosis
9. Necessity of oesophageal stent placement prior to randomisation;
10. Any known relevant infectious disease (e.g., AIDS defining diseases, active tuberculosis);
11. Diagnosis of chickenpox, herpes zoster or measles within the last three months prior to randomisation
12. Known history of a) liver cirrhosis, b) severe renal impairment (Portugal only)
13. Any of the following medical conditions (if not being sufficiently under control): cardiovascular disease, diabetes mellitus, osteoporosis, active peptic ulcer disease, glaucoma, cataract
14. Any severe concomitant disease, which in the opinion of the investigator might have an influence on the patient’s compliance or the interpretation of the results, or any disorder which in the opinion of the investigator might affect the patient’s safety;
15. a) (All countries, except Portugal:) Any systemic therapy for any reason that may affect assessment of primary or secondary endpoints, i.e., biologics, or immunosuppressants, within the last 4 weeks prior to randomisation or planned as concomitant treatment, b) (Portugal only:) Any systemic therapy for any reason that may affect assessment of primary or secondary endpoints, i.e., systemic glucocorticosteroids, biologics, or immunosuppressants, within the last 4 weeks prior to randomisation or planned as concomitant treatment
16. a) (All countries, except Portugal:) Oral or intravenous systemic or oral topical glucocorticosteroids for any reason that may affect assessment of primary or secondary endpoints, which cannot be stopped at screening latest or are planned as concomitant treatment; b) (Portugal only:) Oral topical glucocorticosteroids used within the last 2 weeks prior to randomisation or planned as concomitant treatment
17. Inhaled or nasal topical glucocorticosteroids for any reason that may affect assessment of primary or secondary endpoints, which cannot be stopped at screening latest or are planned as concomitant treatment for more than 7 days;
18. Any therapy with cytochrome P450 3A4 (CYP3A4) inhibitors which might influence hepatic biotransformation: very potent (cobicistat, ritonavir, ketoconazole, voriconazole), potent (boceprevir, clarithromycin, itraconazole, saquinavir, telaprevir, telithromycin), or moderate (aprepitant, conivaptan, diltiazem, erythromycin, fluconazole, nefazodone, posaconazole, verapamil) administered repeatedly (i.e., > 3 days) in the last 3 weeks prior to randomisation or planned as concomitant therapy for more than 7 days;
19. Any therapy with CYP3A4 inducers, which might influence hepatic biotransformation: very potent (carbamazepine, phenytoin, rifampicin), moderate (St. John’s Wort), administered repeatedly (i.e., > 3 days) in the last 3 weeks prior to randomisation or planned as concomitant therapy for more than 7 days;
20. Live vaccination within the last 4 weeks prior to randomisation, or any planned live vaccination during the trial
21. Intake of grapefruit containing food or beverages during the DB treatment phase
22. Known intolerance/hypersensitivity/resistance to the investigational medicinal product (IMP: budesonide) or its excipients or to drugs of similar chemical structure or pharmacological profile;
23. History of intolerance/hypersensitivity to propofol (if propofol will be used for sedation)
24. Well-founded doubt about the patient’s cooperation
25. Existing or intended pregnancy or breast-feeding;
26. Participation in another clinical trial within the last 30 days prior to the screening visit, simultaneous participation in another clinical trial, or previous participation in the BUL-5 trial and having received any IMP

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients free of strictures at visit week 8

Secondary endpoints 2

1. Number of endoscopic dilations per patient during the DB treatment phase
2. Percentage of patients free of strictures until the FU visit

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dr. Falk Pharma GmbH

Sponsor organisation

Dr. Falk Pharma GmbH

Address

Leinenweberstrasse 5, Hochdorf Hochdorf

City

Freiburg Im Breisgau

Postcode

79108

Country

Germany

Scientific contact point

Organisation

Dr. Falk Pharma GmbH

Contact name

Dept. of Clin. Res. & Development

Public contact point

Organisation

Dr. Falk Pharma GmbH

Contact name

Dept. of Clin. Res. & Development

Third parties 7

Locations

7 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 71 files

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

Application history

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