E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oral chronic graft versus host disease as a complication of haematopoietic stem cell transplantation. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066261 |
E.1.2 | Term | Chronic graft versus host disease |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
To assess the rinse´s safety and tolerability in the form of adverse events and laboratory parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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 |
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E.4 | Principal 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) 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of objective response at the final/withdrawal visit using NIH scale (15-point Schubert scale) and WHO response criteria. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |