Double-blind, randomised, placebo-controlled multicentre phase III clinical study followed by open-label phase on the efficacy and tolerability of budesonide 3 mg effervescent tablet in patients with resistant oral chronic GvHD - ND

• Conditions: Chronic Graft versus Host Disease; MedDRA version: 12.1Level: LLTClassification code 10066261Term: Chronic graft versus host disease

• Registration Number: EUCTR2008-004562-10-IT
• Lead Sponsor: DR. FALK PHARMA GMBH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-15
• Last Update Posted: 14 March 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

1. Signed informed consent 2. Man or woman between 18 and 75 years of age 3. Karnofsky ≥ 70 4. Oral chronic GvHD after allogeneic haematopoietic stem cell transplantation (cGvHD defined as GvHD present beyond day 100 post-transplantation) 5. Oral cGvHD confirmed by presence of at least one diagnostic clinical sign of cGvHD or presence of at least one distinctive manifestation confirmed by pertinent biopsy or other relevant tests1 6. Oral cGvHD of erosive and/or ulcerative type 7. NIH scale (15-point Schubert scale) ≥ 3 but at least score 3 (moderate) for ulcers or at least score 2 (moderate) for erythema (lichenoid has to be present in case of absence of ulcers) 8. Resistant oral cGvHD with no oral response defined as the lack of partial response to conventional primary treatment (i.e. systemic prednisone and/or cyclosporine) after 4 weeks 9. In case of conventional primary treatment (i.e. systemic prednisone and/or cyclosporine) dosage unchanged within the last 4 weeks before inclusion (dose reduction and dose adjustment by therapeutic drug monitoring [TDM] allowed) 10. In case of treatment with tacrolimus (FK506), sirolimus (rapamycin), or mycophenolate mofetil (MMF) dosage unchanged within the last 4 weeks before inclusion (dose reduction and dose adjustment by TDM allowed) 11. Negative pregnancy test at baseline visit week 0 in females of childbearing potential 12. Male or female patients with reproductive potential must use an approved contraceptive method during study treatment evaluation
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Uncertain diagnosis of resistant oral cGvHD 2. Symptomatic oral cGvHD of hyperkeratotic type solely 3. Current active oral bacterial, viral, or fungal infection 4. Unwilling to forego concurrent treatment for mucosal lesions and/or related oral pain (including viscous lidocaine, topical antifungals, or mouthwashes) 5. Requiring addition of new systemic therapy including steroids, or radiation therapy 6. Local intestinal infection 7. Abnormal hepatic function or liver cirrhosis (ALT or AST > 3 x ULN; in case of hepatic cGvHD: Bilirubin > 3 x ULN and/or ALT or AST > 5 x ULN. 8. If careful medical monitoring is not ensured: tuberculosis, cardiovascular disease, diabetes mellitus, osteoporosis, active peptic ulcer disease, glaucoma, cataract, infection 9. Second line treatment of oral cGvHD with topical steroids (e.g. dexamethasone, beclomethasone) within the last 4 weeks 10. Use of inhaled steroids for the treatment of e.g. COPD or bronchiolitis 11. Treatment with low dose total lymphoid irradiation, intraoral PUVA, extracorporeal photochemotherapy, thalidomide, pentostatin within the last 4 weeks 12. Treatment with ketoconazole, itraconazole or other CYP3A inhibitors except fluconazole, voriconazole, cyclosporine, and tacrolimus/FK506 (increase of dose not allowed, see inclusion criteria 9 and 10) 13. Unable to demonstrate appropriate use of study medication 14. Existing or intended pregnancy or lactation 15. Known intolerance/hypersensitivity to study drugs or drugs of similar chemical structure or pharmacological profile 16. Participation in another clinical study for the treatment of cGvHD within the last 30 days or simultaneous, or previous participation in this study 17. Well-founded doubt about the patient s cooperation, e.g. because of addiction to alcohol or drugs

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of the budesonide 3 mg effervescent tablet rinse vs. placebo rinse in decreasing the severity of oral cGvHD and oral cGvHDrelated mouth pain.;Secondary Objective: To assess the rinse s safety and tolerability in the form of adverse events and laboratory parameters.;Primary end point(s): Rate of objective response at the final/withdrawal visit using NIH scale (15-point Schubert scale) and WHO response criteria