E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric allogeneic stem cell transplant recipients at high risk of Adenovirus infection |
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E.1.1.1 | Medical condition in easily understood language |
Children at risk of adenovirus infection following bone marrow transplant |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060931 |
E.1.2 | Term | Adenovirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 safety of ADV specific T cells. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the pharmacokinetics (PK) of ADV specific T cells with respect to absolute T cell counts • Time to absence of ADV viraemia • Use of antiviral and other anti-infective drugs • Time in-hospital stay |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The patient inclusion criteria will include: 1) Age < 16 years of age (please note that only patients that will remain below the age of 16 years until their study completion should be included as suitable participants) 2) Laboratory tests as described in Appendix 6. 3) Recipient of allo-HSCT with in vivo or ex vivo T cell depletion from matched unrelated, mis-matched unrelated or family donor, or haploidentical donor
Patient Inclusion Criteria – for study enrolment and cell infusion (Treatment Phase) A patient will be eligible for enrolment in the study if, in addition to the screening patient inclusion criteria listed above, all of the following criteria apply: 1) For all subjects, a parent or legal guardian must give informed consent. Patients aged 11-15 will be encouraged to provide witnessed written assent. 2) The patient has two consecutive positive ADV PCR results >1000 copies/ml
Donor Inclusion Criteria Eligible unrelated, haploid or mismatched family donors will have already passed a medical for stem cell donation. The donor inclusion criteria will include: 1) The donor will be selected from a registry that has approved the protocol and consent procedure. 2) Donor must have met all regulatory requirements for transplant. 3) Laboratory tests as described in Appendix 6 4) Healthy donor – having passed medical for stem cell donation 5) Negative serology for HIV (type 1 & 2), Hepatitis B and C and Syphilis 6) Written informed consent 7) Age 16 years or older
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E.4 | Principal exclusion criteria |
Patient Exclusion Criteria – for the cell infusion of Cytovir ADV A patient will NOT be eligible for enrolment in the study if any of the following criteria are met: 1) Acute GvHD ≥ Grade II 2) Significant pneumonitis 3) Significant hepato-biliary disease Please note the patient exclusion criteria should be reviewed immediately prior to each cell product infusion; cells should not be infused into patients meeting any of the exclusion criteria. In the event that any exclusion criteria are met cell infusion may be delayed until such events have resolved.
Donor Exclusion criteria in accordance with registry criteria 1) Pregnant or lactating and to be assessed prior to donation: 2) Platelets < 50x109/L |
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E.5 End points |
E.5.1 | Primary end point(s) |
Toxicity: incidence and severity of GvHD, cytopaenias, grade 3-4 Adverse Events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day -28 (HSCT Procedure), -2 (HSCT procedure - follow up), 0 (administration of Cytovir ADV), Day +14, 30, 90, 120, 150, 180 days post-administration of Cytovir ADV infusions |
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E.5.2 | Secondary end point(s) |
• Number of reported serious adverse events (SAEs) (Suspected, Unexpected Serious Adverse Reactions [SUSARs] and Suspected, Expected Serious Adverse Reactions [SESARs]) • Viral clearance, absolute (by PCR) ADV viraemia at each time point • Requirement for second infusion of ADV specific T cells • Number of treatment days with antiviral drugs • Number of treatment days with other anti-infective drugs • Number of in-hospital days during study period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day -28 (HSCT Procedure), -2 (HSCT procedure - follow up), 0, 7, 14, 21, 28, 42, 56, 70, 87, 120, 150, 180 |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 28 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 29 |