E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
AdV infection in pediatric and adult allo HCT recipients receiving standard of care |
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E.1.1.1 | Medical condition in easily understood language |
Adenovirus infection in child and adult patients who received hematopoietic cell transplant (cells involved in the formation of blood cells) and are receiving standard of care treatment. |
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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 | 21.1 |
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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
PRIMARY EFFICACY To compare the percent of participants who have clearance of AdV viremia at Day 29 in participants receiving posoleucel and SoC to that in participants receiving placebo and SoC.
PRIMARY SAFETY To determine the safety and tolerability of posoleucel by analyzing the incidence and severity of treatment-emergent adverse events (TEAEs), including individual AEs of special interest (AESIs).
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E.2.2 | Secondary objectives of the trial |
1) To determine the percent of participants who develop target organ AdV disease or whose target organ disease progresses during the study.
2) To evaluate the effect of posoleucel on AdV viremia over a 28-day period.
3) To determine the percent of participants who develop target organ AdV disease or whose target organ disease progresses by Day 29.
4) To determine the percentage of participants who achieve AdV viremia <400 copies/mL AdV DNA.
5) To assess the effect of posoleucel on time to clearance of AdV viremia.
6) To evaluate the proportion of participants who have recurrence of viremia (≥10,000 copies/mL AdV DNA) and/or target organ disease during the study
7) To evaluate the proportion of participants who are target organ disease-free at Day 29 and at the end of the study. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female of any age. 2. Has undergone allogeneic (including umbilical cord) cell transplantation ≥21 days prior to dosing and has demonstrated engraftment with an absolute neutrophil count >500/mm3, AND has one of the following:
a. AdV viremia DNA ≥10,000 copies/mL at screening, OR b. Two consecutive and rising AdV viremia DNA results of ≥1,000 copies/mL at screening, AND i. has absolute lymphocyte count <180/mm3, OR ii. has received T cell depletion, OR iii. had a cord blood transplant.
3. Males and females of childbearing potential who engage in heterosexual intercourse must agree to use contraception as detailed in Appendix 5 of this protocol and refrain from donating sperm or eggs for at least 90 days after treatment completion. 4. Willing and able to provide signed informed consent. 5. Has an HLA type matching with at least 1 suitably matched and available posoleucel VST line for infusion. |
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E.4 | Principal exclusion criteria |
1. Grade 3 or higher acute GVHD (see Appendix 6 for information on acute GVHD grading and severity). 2. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day or equivalent). Patients actively undergoing corticosteroid tapering during Screening may randomize and dose once they have reached ≤ 1.0 mg/kg/day with Medical Monitor approval, with the expectation that the corticosteroid taper will continue. 3. Has either of the following laboratory parameters at screening: a. Aspartate aminotransferase and alanine aminotransferase serum levels ≥5 times the upper limit of normal (ULN), OR b. Direct bilirubin serum levels ≥3 times the ULN. 4. Relapse of primary malignancy, or any other active malignancy, except for non-melanoma skin cancer. Malignancies that are slow growing and/or stable may be allowed with Medical Monitor approval. 5. Grade 4 diarrhea (ie, life-threatening consequences with urgent intervention indicated) regardless of attribution ongoing or within 7 days prior to randomization. 6. Uncontrolled viral (other than AdV), bacterial, or fungal infection(s) leading to hemodynamic instability or radiologic or laboratory evidence attributable to worsening disease. 7. Requirement for fraction of inspired oxygen (FiO2) >0.5 (ie, 50%) to maintain arterial oxygen saturation >90% (via pulse oximetry) or need for mechanical ventilation, except for planned procedures or surgeries with Medical Monitor approval. 8. Prior therapy with anti-thymocyte globulin, alemtuzumab (Campath®), or other immunosuppressive T cell monoclonal antibodies within 28 days prior to dosing. 9. Prior donor lymphocyte infusion or CD34+ stem cell infusion within 21 days prior to dosing.
Other protocol-defined criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Proportion of participants with undetectable viremia (less than lower limit of quantitation [LLOQ]) at Day 29.
2) Incidence and severity of TEAEs, including individual AESIs, during the study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) baseline, Day 29 2) baseline through EoT |
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E.5.2 | Secondary end point(s) |
1) Proportion of participants with disease progression or non-relapse mortality during the study.
2) Proportion of participants with undetectable viremia (less than LLOQ) at Day 29 in participants - without AdV disease at screening. - with AdV disease at screening.
3) Time-averaged area under the concentration-time curve (AAUC) for plasma AdV viremia (log10 copies/mL AdV DNA) as assayed by quantitative polymerase chain reaction (qPCR) through Day 29 for all participants.
4) AAUC for plasma AdV viremia (log10 copies/mL AdV DNA) as assayed by qPCR through Day 29 for participants with no target organ disease at screening.
5) Proportion of participants with disease progression or non-relapse mortality by Day 29.
6) Proportion of participants who achieve AdV viremia <400 copies/mL AdV DNA at Day 29.
7) Time to undetectable AdV viremia (less than LLOQ).
8) Proportion of participants with AdV disease recurrence during the study among participants who had clearance of AdV viremia (prior to any cross-over)
9) Proportion of participants who are target organ disease-free at Day 29 and at the end of the study. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1,2,5,6) baseline, Day 29 3,4) baseline through Day 29 7,8) baseline through EoT 9) baseline, Day 29, EoT
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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 | 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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 |
Canada |
United Kingdom |
United States |
Italy |
Spain |
Sweden |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 10 |