E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The proposed indication for Prochymal™ is for the treatment of subjects who have failed to respond to steroid treatment of acute graft-versus-host disease (GVHD), post allogeneic hematopoietic stem cell transplant (HSCT) or post donor leukocyte infusion (DLI).
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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 | 10018651 |
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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 |
1) To evaluate the efficacy of Prochymal in subjects with Grades B-D acute GVHD, who have failed to respond to steroid treatment. |
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E.2.2 | Secondary objectives of the trial |
2) To gather additional information on the safety of Prochymal in subjects with Grades B-D acute GVHD, who have failed to respond to steroid treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects must be 6 months to 70 years of age, inclusive • Subjects who have failed to respond to steroid treatment: Failure to respond to steroid treatment is defined as any Grade B-D (IBMTR grading) of acute GVHD that shows: - No improvement after 3 days and - A duration of no greater than 2 weeks while receiving treatment with Methylprednisolone (≥ 1 mg/kg/day) or equivalent. • Subjects must be able to be treated within 4 days of randomization. In urgent situations 2nd line therapy may be started 24 hours prior to randomization, and Prochymal must be initiated within the following 3 days. • Subjects with persistent GI GVHD manifested by diarrhea with stool volume < 500 mL/day in the absence of nausea or vomiting may be deemed as having grade B GVHD if other causes of diarrhea have been ruled out (e.g., C. difficile or CMV infection, oral magnesium administration) and if the low stool volume reflects the effects of fasting or administration of narcotics or anti-diarrheal medications. • Subjects who may have received an increase in their steroid dose treatment prior to randomization will be eligible for enrollment. An increase in steroid dose will not be considered as second line therapy. • Subjects must have adequate renal function as defined by: For adult patients: Calculated Creatinine Clearance of >30mL/min using the Cockroft-Gault equation For pediatric patients: Schwartz equation (Patient population: infants over 1 week old through adolescence (<18 years old) • Subjects who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male subjects must use adequate contraception. • Subject must have a minimum Karnofsky/Lansky Performance Level of at least 30 at the time of study entry. • Subject (or legal representative where appropriate) must be capable of providing written informed consent. |
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E.4 | Principal exclusion criteria |
•Subject has started treatment with second line therapy > 24 hours prior to randomization. • Subject has received agents other than steroids for primary treatment of acute GVHD • Subject has evidence of a pulmonary infiltrate or diffuse alveolar hemorrhage and is likely to require more than 2L of oxygen via face mask or an estimated FiO2 of 28% via other delivery methods in order to sustain an O2 saturation of 92% during the next 3 days. • Subject is participating in the CTN Protocol 0302 • Subject has any underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the subject including uncontrolled infection, heart failure, pulmonary hypertension, etc. • Subjects may not receive any other investigational agents (not approved by the FDA for any indication) concurrently during study participation or within 30 days of randomization. • Subject has a known allergy to bovine or porcine products. • Subject has received a transplant for a solid tumor disease. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint Complete response with >/= 28 days duration
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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 | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 13 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 17 |