Study of ALVR106 in Patients With Respiratory Viral Infections After Hematopoietic Cell Transplant

Study Overview
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Brief Summary
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A study to evaluate ALVR106; an allogeneic, off-the-shelf multi-virus specific T cell therapy that targets four community acquired respiratory viruses: respiratory syncytial virus (RSV), influenza, human metapneumovirus (hMPV), and/or parainfluenza virus (PIV) following hematopoietic cell transplant (HCT)

Detailed Description
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The study hypothesis is that the administration of ALVR106, multi-virus specific T cells, plus standard of care, to post HCT patients suffering from infection with any of the four targeted viruses (RSV, influenza, hMPV, and/or PIV) will be safe and demonstrate shorter time to resolution of the respiratory viral infection (as measured by resolution of symptoms and viral load clearance in nasal swab) compared to patients treated with placebo. This trial will consist of two parts: Part A - Dose Escalation in Patients with Upper Respiratory Tract Infections (URTI) at High-Risk of Progression to Lower Respiratory Tract Infections (LRTI) Part B - Recommended Phase 2 Dose (RP2D) cohort expansion in patients with URTIs at high-risk of progression to LRTIs

Official Title
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Phase 1/2, Double-Blind, Placebo-Controlled, Dose Escalation and Expansion Study of ALVR106 in Addition to Standard of Care for the Treatment of High-Risk Patients With Respiratory Viral Infections After Hematopoietic Cell Transplant

Conditions
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Respiratory Tract Viral Infections, Human Metapneumovirus (hMPV) Infection, Parainfluenza (PIV) Infection, Respiratory Syncytial Viral (RSV) Infection, Influenza Infection

Intervention / Treatment
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* Biological: ALVR106
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergone allogeneic, autologous, or cord blood stem cell transplantation at least 21 days prior to randomization Detection of at least 1 target virus of interest (ie, RSV, influenza, hMPV, and/or PIV) Diagnosis of Upper Respiratory Tract Infection Exclusion Criteria: Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose >0.5 mg/kg/day) Prior therapy with antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted monoclonal antibodies within 28 days Proven or suspected infection by novel coronavirus disease 2019 (COVID-19) within 28 days Evidence of Grade >2 acute graft versus host disease (GVHD) Receipt of another investigational antiviral treatment within 28 days Donor lymphocyte infusion or other T cell therapies performed <21 days prior to randomization

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 75 Years

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo, visually identical to ALVR106 | Biological: Placebo<br>* Infusion, visually identical to ALVR106<br>|
| Active Comparator: ALVR106<br>ALVR106, visually identical to placebo | Biological: ALVR106<br>* Infusion, visually identical to placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of ascending doses of ALVR106 assessed through Adverse Events and Clinical Laboratory tests | Number (%) of patients with adverse events (AEs) according to severity, seriousness, and relationship to study drug and number (%) of patients with clinically significant change from baseline in laboratory abnormalities as characterized by type, frequency, severity (graded by CTCAE version 5.0) | Up to Day 365 | 
| Change in viral load (Part B) | Change from Baseline in viral load as measured by quantitative PCR of nasal swab | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in viral load | Change from Baseline in viral load as measured by quantitative PCR of nasal swab | Up to Month 6 | 
| Progression from URTI to LRTI | Proportion of patients with progression to LRTI | Day 10, Day 28 | 
| Identify the recommended Phase 2 (RP2D) (Part A) |  | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory virus, Hematopoietic Cell Transplant, Upper Respiratory Tract Infection, Bone Marrow Transplant, Human Metapneumovirus Infection, Parainfluenza, Respiratory Syncytial Virus (RSV), Multi-virus specific T cells (VST)