E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Graft versus host disease |
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E.1.1.1 | Medical condition in easily understood language |
Acute 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 |
Key Secondary Objective is to evaluate the efficacy of AAT for the prevention of severe aGVHD and infections following HCT. Also, 1. To further evaluate the efficacy of AAT for the prevention of complications after HCT. 2. To evaluate the safety of AAT based on investigational product- (IP)- related AEs. 3. To evaluate the steady state PK 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 in Part 1 (≥ 18 years of age fore subjects at German sites only), undergoing HCT for hematological malignancies, including leukemia, lymphoma and multiple myelomamyelodysplastic syndrome and myeloproliferative neoplasms. 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 (ie, anti-thymocyte globulin [ATG],alemtuzumab) for GVHD prophylaxis 3. Planned umbilical cord blood (UCB) transplant |
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E.5 End points |
E.5.1 | Primary end point(s) |
The time to Grade II-IV aGVHD or death
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Through 180 days after post-hematopoietic cell transplantation (HCT)
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E.5.2 | Secondary end point(s) |
1) Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ 2) Proportion of subjects with severe infections defined by NCI-CTCAE = Grade 3 3) Proportion of subjects with Grade II-IV aGVHD or death 4) Proportion of subjects with lower GI aGVHD 5) Proportion of subjects with lower GI aGVHD 6) Proportion of subjects with severe infections defined by NCI-CTCAE = Grade 3 7) Proportion of subjects with Grade III-IV aGVHD or death 8) Proportion of subjects with moderate-to-severe chronic GVHD 9) Proportion of subjects who have discontinued immune suppression therapies including standard-of-care GVHD prophylaxis and steroid treatment 10) Time to neutrophil engraftment 11) Time to GVHD relapse-free survival 12) Proportion of subjects with relapse of primary malignancies 13) Proportion of subjects with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response 14) Percent of subjects with study drug-related adverse events 15) Maximum concentration (Cmax) of AAT 16) Area under the concentration curve for AAT 17) Clearance of AAT 18) Volume of distribution for AAT 19) Ctrough of AAT
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Through 180 days after HCT 2) Through Day 60 after HCT 3) Through 100 and 180 days after HCT 4) Through Days 60, 100 and 180 after HCT 5) Within 180 and 365 and 730 days after HCT 6) Through 100 and 180 days after HCT 7) Through Days 60, 100, and 180 days after HCT 8-9) Within 180,365,545 and 730 and days after HCT 10) Through 365 days after HCT 11) Within 365 and 730 days after HCT 12) Through 180, 365 and 730 days after HCT 13) Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period 14) Up to 365 days after HCT 15-19) 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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Japan |
Korea, Republic of |
United States |
Spain |
Germany |
Italy |
Turkey |
United Kingdom |
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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 | 8 |
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 | 8 |