Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of Posoleucel for the treatment of adenovirus (AdV) infection in pediatric and adult allo-HCT recipients receiving standard of care (SoC).

Detailed Description
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During the period of immune recovery after allogeneic hematopoietic cell transplant (allo-HCT), viral infections and reactivations, including those with AdV, are an important cause of morbidity and mortality. Progression to AdV disease is associated with significant morbidity and mortality rates. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study will assess the safety and efficacy of Posoleucel for the treatment of AdV infection in pediatric and adult allo-HCT recipients receiving SoC.

Official Title
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Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, With Cross-Over, of Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following Allogeneic Hematopoietic Cell Transplantation

Conditions
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Adenovirus Infection

Intervention / Treatment
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* Drug: Posoleucel
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergone allogeneic cell transplantation ≥21 days prior to dosing Meet one of the below criteria: AdV viremia DNA ≥10,000 copies/mL, OR AdV viremia DNA results of ≥1,000 copies/mL, AND has absolute lymphocyte count <180/mm3, OR has received T cell depletion OR had a cord blood transplant. Exclusion Criteria: Grade 3 or higher acute GVHD Ongoing therapy with high-dose systemic corticosteroids Uncontrolled viral (other than AdV), bacterial, or fungal infection(s) Pregnant or lactating female unwilling to discontinue nursing prior to randomization History of severe prior reactions to blood product transfusions NOTE: Other protocol-defined inclusion/exclusion criterion may apply.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study with option for blinded crossover to assess the safety and efficacy of posoleucel as compared to placebo for the treatment of AdV infection in pediatric and adult recipients of HCT with AdV infections receiving SoC.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Posoleucel + SoC<br>Posoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria | Drug: Posoleucel<br>* Administered as 2-4 milliliter infusion, visually identical to placebo<br>|
| Placebo Comparator: Placebo + SoC<br>Placebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria | Drug: Placebo<br>* Administered as 2-4 milliliter infusion, visually identical to Posoleucel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with undetectable adenovirus infection | Primary Efficacy | 29 days | 
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Primary Safety | 34 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall disease progression or non-relapse mortality | Key Secondary Efficacy | 34 weeks | 
| Mean area under the curve (AUC) AdV viral load | Other Secondary Efficacy | 29 days | 
| Proportion of participants who achieve AdV viremia <400 copies/mL | Other Secondary Efficacy | 29 days | 
| Time to undetectable AdV viremia (less than LLOQ) | Other Secondary Efficacy | 34 weeks | 
| Incidence of AdV disease recurrence | Other Secondary Efficacy | 34 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenovirus, Allogeneic Hematopoietic Cell Transplant, Adenoviremia, Stem Cell Transplant, Posoleucel, ALVR105, Bone Marrow Transplant