E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with acute gastrointestinal Graft Versus Host Disease. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064677 |
E.1.2 | Term | Graft versus host disease in intestine |
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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 |
The primary objective of this confirmatory, multi-center study is to compare the efficacy, defined as the proportion of subjects who are GVHD treatment successes vs. failures, of an oral BDP regimen consisting of an induction course of prednisone [1 mg/kg/day for ten (10) days] plus 8 mg/day BDP for fifty (50) days, with the efficacy of an induction course of prednisone [1 mg/kg/day for ten (10) days] plus placebo tablets for fifty (50) days, in subjects with acute gastrointestinal (GI) GVHD. |
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E.2.2 | Secondary objectives of the trial |
a. Cumulative prednisone exposure (in mg/kg/day) received while under observation during the 80-day study period. b. The occurrence of GVHD treatment failure during the 50-day study drug treatment period. c. Survival status at Study Day 200 post-randomization. d. The presence or absence of active acute GI GVHD at Study Day 110. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
POPULATION PHARMACOKINETICS OF BECLOMETHASONE (BOH), BECLOMETHASONE 17-MONOPROPIONATE (17-BMP) AND BECLOMETHASONE 17,21-DIPROPIONATE DURING ORBEC® (ORAL BECLOMETHASONE 17,21-DIPROPIONATE) TREATMENT OF ACUTE GASTROINTESTINAL GRAFT-VS-HOST DISEASE (GI GVHD) IN PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION: A PHARMACOKINETIC SUBSTUDY OF THE PHASE 3 STUDY BDP-GVHD-03 |
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E.3 | Principal inclusion criteria |
1)Patients must be between 10 and 100 days post-allogeneic hematopoietic cell transplantation. 2) Symptoms consistent with GI GVHD with endoscopic evidence of GVHD without another plausible explanation for symptoms. 3) Histologic diagnosis of GVHD within ninety-six (96) hours prior to the first dose of study drug. 4) Absence of GI infection within seven (7) days prior to the first dose of study drug. (For patients with diarrhea, no stool pathogens can be detected; for patients undergoing endoscopic biopsies, no infectious agents can be found). 5) Demonstrated ability to swallow two (2) tablets of the size and configuration of study drug. 6) Anti-candidal prophylaxis with an effective drug prior to the first dose of study drug. 7) If female and of childbearing potential, must be willing to use adequate contraception, as determined by the investigator, for the duration of the study. 8) Ability to read, understand, and sign (or have legal representative sign) appropriate patient informed consent. 9) ≥ (> or =) 18 years of age. |
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E.4 | Principal exclusion criteria |
1) Skin GVHD, other than a slowly evolving rash that involves ≤ (< or =) 50% of the body surface. 2) Definite liver GVHD by liver histology or clinical criteria or evidence of liver dysfunction with a total serum bilirubin >3 mg/dL plus conjugated (direct) serum bilirubin >1.0 mg/dL. 3) >1000 mL/day diarrhea on any one (1) day within three (3) days prior to first dose of study drug. 4) Systemic (oral or IV) corticosteroid use for the purpose of prophylaxis or treatment of GVHD or another inflammatory disease process within thirty (30) days prior to first dose of study drug. Exceptions include: use of corticosteroids as anti-emetics during conditioning therapy, or as a pre-medication for infusion of blood products or, < 2 days of stress coverage. If immediate treatment for presumptive GVHD is clinically indicated, up to two doses of prednisone or equivalent (totaling 1mg/kg/day) may be given while awaiting biopsy results in the 24 hours prior to start of study drug. 5) Persistent vomiting of oral intake that precludes ingestion of study drug tablets. 6) Multi-organ failure, sepsis syndrome, or other condition with high mortality (i.e., life expectancy less than 3 months). 7) Infection of the mouth or esophagus with a fungal organism. 8) Known HIV seropositivity. 9) Pregnancy or lactation. 10)Use of any investigational drug, biologic, or device for treatment of GVHD within previous thirty (30) days. 11) In the Investigator’s opinion, an inability to comply with the study procedures and scheduled study visits. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The occurrence (yes/no) during the 80-day study period of GVHD treatment failure defined as use of prednisone or equivalent IV corticosteroids at doses higher than stated in the protocol, or use of any additional other glucocorticoid (including unblinded BDP) or addition of other immunosuppressant medications, in response to uncontrolled signs or symptoms of GVHD. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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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The trial is consider complete when all enrolled subjets have completed all protocol assessments (through Day 200). The only situation where the last visit of the last subject would NOT be the end of the study would be if the patient died or went to hospice prior to other patients completing Study Day 200 or dying. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |