E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adenovirus (AdV), BK virus (BKV), John Cunningham virus (JCV), human herpesvirus 6 (HHV- 6), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) infections and/or disease in patients at high risk for these viruses following allogeneic hematopoietic cell transplant |
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E.1.1.1 | Medical condition in easily understood language |
Adenovirus, BK virus, John Cunningham virus, human herpesvirus 6, Epstein-Barr virus and cytomegalovirus infections/disease in patients at high risk for these viruses 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 | 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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10055181 |
E.1.2 | Term | BK virus 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 | 22.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020431 |
E.1.2 | Term | Human herpesvirus 6 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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10015108 |
E.1.2 | Term | Epstein-Barr virus 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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011831 |
E.1.2 | Term | Cytomegalovirus 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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023163 |
E.1.2 | Term | JC virus 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 |
To compare the efficacy of posoleucel to placebo by the number of clinically significant infections or episodes of end-organ disease per patient due to AdV, BKV, CMV, EBV, HHV-6, or JCV as determined by an independent, blinded Clinical Adjudication Committee (CAC) through Week 14 |
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E.2.2 | Secondary objectives of the trial |
Key Secondary
1. To compare the efficacy of posoleucel to placebo by the number of clinically significant infections or episodes of end-organ disease per patient due to AdV, BKV, CMV, EBV, HHV-6, or JCV as determined by an independent, blinded CAC through Week 26
Secondary:
2. To compare the efficacy of posoleucel to placebo by clinically significant infections or episodes of end-organ disease per patient due to AdV, BKV, CMV, EBV, or HHV-6 due to each individual virus as determined by an independent, blinded CAC through Week 14 and Week 26
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age
1. Any age the day of screening visit. Enrollment of participants <1 year of age at the time of informed consent will occur only once preliminary safety data are available from 5 participants ≥1 and ≤6 years of age.
Type of Participant and Disease Characteristics
2. Has no known or suspected clinically significant disease from AdV, BKV, CMV, EBV, HHV-6, and/or JCV
3. Be within 25 days (+5 days with sponsor approval) after receiving a first allogeneic HCT and have demonstrated clinical engraftment, as evidenced by single absolute neutrophil count (ANC) ≥500/mm3 at the time of dosing.
4. Patients meeting one or more of the following criteria at the time of randomization:
o Human leukocyte antigen (HLA)-related (sibling) donor with at least one mismatch at one of the following three HLA-gene loci: HLA-A, -B or -DR
o Haploidentical donor
o Matched unrelated donor (MUD) with T cell depletion or post transplant cyclophosphamide (Enrollment of patients who received a transplant from a MUD, without T cell depletion or post transplant cyclophosphamide is no longer permitted)
o Mismatched unrelated donor
o Umbilical cord blood as stem cell source
o Ex vivo graft manipulation resulting in T cell depletion
o Received t-cell depletion by antithymocyte globulin (ATG) or alemtuzumab (Campath-1H)
Sex
5. Male and/or female
a. Male participants:
Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 90 days after the last dose of study intervention:
• Refrain from donating sperm PLUS, either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception /barrier as detailed below
• Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant
b. Female participants:
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
• Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4.1 of the protocol
OR
• Is a WOCBP and using a highly effective method of contraception as described in Section 10.4.2 of the protocol during the study intervention period and for at least 90 days after the last dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative serum pregnancy test within 14 days
before the first dose of study intervention, see Section 8.4.7 of the protocol.
• Additional requirements for pregnancy testing during and after study intervention are located in Section 8.4.7 of the protocol.
Informed Consent and Cell Line Match
6. Willing and able to provide written informed consent as described in Section 10.1.3 of the protocol to participate in the study, or a parent or legal guardian is willing and able to provide written informed consent and the potential pediatric patient is able to provide assent in a manner approved by the Institutional Review Board (IRB) and local regulations.
7. 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 |
Medical Conditions
1. Has a history of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization
2. Evidence of active Grade >2 acute GVHD (for additional information on acute GVHD grading and severity, see Appendix 5 [Section 10.5 of the protocol]).
3. Presence of non-minor uncontrolled or progressive bacterial or fungal infections (ie, evidence of bacteremia, fungemia, disseminated, and/or organ-specific infection not well controlled by present therapies)
4. Presence of any progressive, uncontrolled viral infections (ie, evidence of viremia (eg HIV, HCV, HBV), dissemination, and/or organ-specific infection not well controlled by present therapies).
5. Known history or current (suspected) diagnosis of Grade ≥3 CRS or ICANS (immune effector cell-associated neurotoxicity syndrome) requiring treatment associated with the administration of peptides, proteins, and/or antibodies, see Appendix 6 [Section 10.6 of the protocol]).
6. Evidence of encephalopathy at randomization
7. Relapse of primary malignancy other than minimal residual disease.
Prior/Concomitant Therapy
8. Donor lymphocyte infusion performed within 21 days prior to randomization
9. All approved antiviral prophylactic medications/doses are permitted. Patients receiving treatment regimens or their pediatric dosing equivalents such as the following at time of dosing are excluded:
• ganciclovir, foscarnet, cidofovir, maribivir, or rituximab at any dose
• valganciclovir (at doses > 900 mg per day)
10. Use of any investigational antiviral agent, including brincidofovir, at the time of dosing or actively receiving any investigational agent at dosing.
11. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >1.0 mg/kg/day) within 24 hours prior to dosing
12. ATG, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies within 21 days prior to dosing (patients who have received prior therapy with cyclophosphamide at any time are eligible for study participation)
13. Receipt of mechanical ventilation of any type, within 1 month prior to treatment (unless related to airway control)
14. Undergoing dialysis at randomization
Prior/Concurrent Clinical Study Experience
15. Received a previous allogeneic HCT (Note: Receipt of a previous autologous HCT is acceptable)
Diagnostic Assessments
16. Aspartate aminotransferase or alanine aminotransferase serum levels >5× the upper limit of normal (ULN) or direct bilirubin serum levels >3× the ULN prior to dosing.
Other Exclusions
17. Pregnant, breastfeeding, or planning to become pregnant during the study.
18. Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere per day),with the patient's participation for the full duration of the study, or would be put at undue risk as judged by the Investigator, such that it is not in the best interest of the patient to participate in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The number of clinically significant infections or episodes of end-organ disease per patient due to AdV, BKV, CMV, EBV, HHV-6, or JCV as determined by an independent, blinded CAC through Week 14 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Key endpoints
1. The number of clinically significant infections or episodes of end-organ disease per patient due to AdV, BKV, CMV, EBV, HHV-6, or JCV as determined by an independent, blinded CAC through Week 26
Endpoints
2. Clinically significant infections or episodes of end-organ disease per patient due to AdV, BKV, CMV, EBV, or HHV-6, from each individual virus as determined by an independent, blinded CAC through Week 14 and Week 26 (5 endpoints each at Week 14 and Week 26)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key Endpoints
1.through Week 26
Endpoints
2. through Week 14 and Week 26
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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 | 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) | 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 | Yes |
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.8.2.4 | 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 | 27 |
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 |
United States |
Turkey |
Belgium |
France |
Italy |
Spain |
Korea, Republic of |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |