E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Graft versus host disease |
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E.1.1.1 | Medical condition in easily understood language |
Graft-versus-host disease is a complication that frequently occurs following hematopoietic cell transplantation when the transplanted cells attack the patients’ organs leading to organ damage. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018651 |
E.1.2 | Term | Graft versus host disease |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 evaluate the efficacy of AAT at the selected dose for the prevention of acute GVHD following HCT. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of AAT, including the prevention of post-hematopoietic cell transplant complications.
2. To evaluate the safety of AAT, based on incidence of systemic infections and related adverse events.
3. To evaluate the pharmacokinetics of AAT in HCT recipients.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects, ≥12 years of age (≥ 18 years of age for subjects at German sites only who are enrolled into Part 2), undergoing HCT for hematological malignancies, including leukemia, lymphoma multiple myeloma, MDS and MPN
2. Planned myeloablative conditioning regimen
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E.4 | Principal exclusion criteria |
1. Prior autologous or allogeneic HCT
2. T-cell depleted transplant or planned use of anti-T cell antibody therapy either ex vivo or in vivo
3. Planned umbilical cord blood (UCB) transplant |
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E.5 End points |
E.5.1 | Primary end point(s) |
Grade II-IV acute graft versus host disease-free survival (aGFS)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through 180 days post-hematopoietic cell transplantation (HCT)
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E.5.2 | Secondary end point(s) |
-Percent of subjects with Grade II-IV aGVHD or death (aGFS)
-Percent of subjects with Grade II-IV acute GVHD
-Percent of subjects with Grade III-IV acute GVHD
-Number of subjects with all-cause mortality
-Percent of subjects with Grade II aGVHD
-Percent of subjects with Grade III aGVHD
-Percent of subjects with Grade IV aGVHD
-Time to all-cause mortality
-Time to non-relapse mortality
-Percent of subjects with moderate-to-severe chronic GVHD
-Percent of subjects with discontinuation of immune suppression
-Time to neutrophil engraftmen
-Time to GVHD relapse-free survival
-Percent of subjects with relapse of primary malignancies
-Percent of subjects with systemic infections
-Percent of subjects with study drug related adverse events
-Maximum concentration (Cmax) of AAT
-Area under the concentration curve (AUC) for AAT
-Clearance (CL) of AAT
-Volume of distribution (V) for AAT |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Through 100 days and 180 days post-HCT
-Within 100 and 180 days post-HCT
-Within 100 and 180 days post-HCT
-Within 180 and 365 days post-HCT
-Within 100 and 180 days post-HCT
-Within 100 and 180 days post-HCT
-Within 100 and 180 days post-HCT
-Up to 365 days post-HCT
-Up to 365 days post-HCT
-Within 180 and 365 days post-HCT
-Within 180 and 365 days post-HCT
-Up to 365 days post-HCT
-Up to 365 days post-HCT
-Within 180 and 365 days post-HCT
-At Days 60 and 180 post-HCT
-Up to 365 days post-HCT
-Before and up to 72 after infusion of AAT
-Before and up to 72 after infusion of AAT
-Before and up to 72 after infusion of AAT
-Before and up to 72 after infusion of AAT |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Sequential: Subjects receive interventions after reaching prior milestones, eg dose escalation stud. |
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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.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 14 |
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 | No |
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 |
Australia |
Canada |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |