In this clinical study, a new drug, Budesonid 3 mg effervescent tablet forthe preparation of a mouth rinse solution to treat oral chronic GvHD(Graft versus Host Disease) resulting from allogeneic (taken fromdifferent individuals of the same species) haematopoietic (blood cellforming) stem cell transplantation (HSCT), is evaluated.

Conditions: Oral chronic graft versus host disease as a complication of haematopoietic stem cell transplantation.
MedDRA version: 17.1Level: PTClassification code 10066261Term: Chronic graft versus host diseaseSystem Organ Class: 10021428 - Immune system disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2008-004562-10-AT

Lead Sponsor: Dr. Falk Pharma GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 224

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 tests
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 or no need for systemic immunosuppression due to oral cGvHD only (mild involvement of 2nd organ allowed, excluding lung involvement) for at least 12 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); 2 weeks acceptable in case of oral cGvHD for more than 6 months without any response to high-dose systemic prednisone and/or cyclosporine
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 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54

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 except prophylactic treatment to prevent infection (see 5.7 Standard of Care)
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 (allowed after 6 months of unsuccessful therapy with unchanged
dosage within the last 4 weeks before inclusion; increase of dosage after study start not allowed), thalidomide, pentostatin within the last 4 weeks
12. Treatment with ketoconazole, itraconazole or other CYP3A inhibitors except fluconazole, posaconazole, 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 versus placebo rinse in decreasing the severity of oral cGvHD and oral cGvHD-related 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.;Timepoint(s) of evaluation of this end point: Study Visit 2-12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Rate of response as defined by NIH<br>• Rate of complete/partial response,<br>stable disease, progressive disease as<br>defined by WHO,<br>• Time to initial objective response,<br>• Rate of improvement in any of the<br>subscores of NIH scale<br>• Rate of subjective improvement<br>(pain, swallowing, swallow foods or<br>liquids),<br>• Reduction in pain,<br>• Duration of mouth pain and use of<br>opiate analgesics following<br>treatment,<br>• Assessment of salivary secretion,<br>• Karnofsky Performance Status,<br>• Duration of use of opiate analgesics,<br>• Weight loss/gain,<br>• Assessment of efficacy by<br>investigator;Timepoint(s) of evaluation of this end point: Study Visit 1-12

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