AdV infection in pediatric and adult allo HCT recipients receiving standard of care MedDRA version: 21.1 Level: PT Classification code 10060931 Term: Adenovirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Posoleucel
Product Code: ALVR105
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Posoleucel
Current Sponsor code: Viralym-M (ALVR105)
Other descriptive name: Allogenei
Sponsors
AlloVir, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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). ;Secondary Objective: 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.;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.;Timepoint(s) of evaluation of this end point: 1) baseline, Day 29 2) baseline through EoT | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;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 | — |
Countries
Canada, Italy, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Line
AlloVir, Inc.
Outcome results
None listed