Human Metapneumovirus (hMPV) Infection, Influenza Infection, Parainfluenza (PIV) Infection, Respiratory Syncytial Viral (RSV) Infection, Respiratory Tract Viral Infections
Conditions
Keywords
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), Solid Organ Transplant (SOT)
Brief summary
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) and solid organ transplant (SOT).
Detailed description
The study hypothesis is that the administration of ALVR106, multi-virus specific T cells, plus standard of care, to post HCT or SOT 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 is Dose Escalation and Part B is Cohort Expansion.
Interventions
BIOLOGICALPlacebo
Infusion, visually identical to ALVR106
BIOLOGICALALVR106
Infusion, visually identical to placebo
Sponsors
AlloVir
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
17 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Undergone hematopoietic cell transplantation (HCT) ≥21 days or solid organ transplantation (SOT) ≥28 days prior to study treatment administration * Detection of at least 1 target virus of interest (ie, RSV, influenza, hMPV, and/or PIV) * Diagnosis of Upper or mild Lower Respiratory Tract Infection
Exclusion criteria
* Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose \>0.5 mg/kg/day) * Infection by novel coronavirus disease 2019 (COVID-19) * For HCT patients, evidence of Grade \>2 GVHD; and for SOT patients, any history or evidence of GVHD
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Day 1 up to 12 months | A TEAE was defined as an adverse event (AE) with a start date and time on or after the first dose of study treatment. A serious AE (SAE) was an AE that met at least one of the following serious criteria: fatal, life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other important medical event. TEAEs of special interest (AESI) included new/worsening graft versus host disease, graft failure or rejection, cytokine release syndrome, infusion related reactions, new/worsening pneumonitis, and progressive dyspnea. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator. |
| Change in Viral Load From Baseline to Day 28 (Part B) | Baseline and Day 28 (Part B) | Change from Baseline in viral load as measured by quantitative PCR of nasal swab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identify the Recommended Phase 2 Dose (RP2D) (Part A) | Day 1 up to 12 months | The RP2D was to be determined after the maximum tolerated dose was reached in Part A. |
| Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A) | Baseline and Day 28 | Viral load was measured by quantitative polymerase chain reaction (PCR) of nasal swab specimens. The cycle threshold value categorizes the concentration of viral genetic material in a participant's swab specimen, and the cycle threshold value represents the number of PCR cycles required to amplify the viral genetic material (as measured by fluorescence) to a detectable level that is distinguishable from baseline fluorescence, providing an estimate of viral load. Lower cycle threshold values indicate higher viral load and high values indicate lower viral load. A positive change from baseline indicates a decrease in the viral load. The baseline measurement was from a pre-dose nasal swab. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part B) | Day 1 up to 12 months | — |
| Percentage Reduction in Viral Load From Baseline to Month 6 (Part B) | Day 1 and Month 6 | — |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study centers in the United States and participated from March 2022 until January 2024.
Pre-assignment details
Participants with respiratory tract infections and clinical manifestations caused by respiratory syncytial virus, influenza virus, human metapneumovirus, and/or parainfluenza virus following hematopoietic cell or solid organ transplants were enrolled. Participants were randomized in a double-blind manner to receive placebo or one of four dose levels of ALVR106, from Dose A (lower dose) to Dose D (higher dose). Due to early study termination, no participants were enrolled into Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo Participants were randomized to receive placebo, and were administered placebo as an IV infusion on Day 1. Participants returned to the clinic for assessments up to Day 14, and based on assessments could receive a second infusion of placebo on Day 14. Participants were followed for up to 12 months. | 2 |
| Part A ALVR106 Cohort 1: Dose A Participants were randomized to receive ALVR106, and were administered ALVR106 Dose A as an IV infusion on Day 1. Participants returned to the clinical site for assessments up to Day 14, and based on assessments could receive a second infusion of ALVR106 Dose A on Day 14. Participants were followed for up to 12 months. | 3 |
| Part A ALVR106 Cohort 2: Dose B Participants were randomized to receive ALVR106, and were administered ALVR106 Dose B as an IV infusion on Day 1. Participants returned to the clinical site for assessments up to Day 14, and based on assessments could receive a second infusion of ALVR106 Dose B on Day 14. Participants were followed for up to 12 months. | 4 |
| Part A ALVR106 Cohort 3: Dose C Participants were randomized to receive ALVR106, and were administered ALVR106 Dose C as an IV infusion on Day 1. Participants returned to the clinical site for assessments up to Day 14, and based on assessments could receive a second infusion of ALVR106 Dose C on Day 14. Participants were followed for up to 12 months. | 4 |
| Part A ALVR106 Cohort 4: Dose D Participants were randomized to receive ALVR106, and were administered ALVR106 Dose D as an IV infusion on Day 1. Participants returned to the clinical site for assessments up to Day 14, and based on assessments could receive a second infusion of ALVR106 Dose D on Day 14. Participants were followed for up to 12 months. | 3 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Missing | 1 | 3 | 2 | 1 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Randomized not treated | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor terminated study | 0 | 0 | 0 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Part A: Placebo | Part A ALVR106 Cohort 1: Dose A | Part A ALVR106 Cohort 2: Dose B | Part A ALVR106 Cohort 3: Dose C | Part A ALVR106 Cohort 4: Dose D | Total |
|---|---|---|---|---|---|---|
| Age, Customized ≤ 18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 19 - 70 years | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 16 Participants |
| Age, Customized ≥ 71 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 3 | 2 / 4 | 2 / 4 | 0 / 3 |
| other Total, other adverse events | 2 / 2 | 3 / 3 | 4 / 4 | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 2 | 2 / 3 | 3 / 4 | 3 / 4 | 1 / 3 |
Outcome results
Primary
Change in Viral Load From Baseline to Day 28 (Part B)
Change from Baseline in viral load as measured by quantitative PCR of nasal swab
Time frame: Baseline and Day 28 (Part B)
Population: No participants were enrolled into Part B due to the early termination of the study.
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A)
A TEAE was defined as an adverse event (AE) with a start date and time on or after the first dose of study treatment. A serious AE (SAE) was an AE that met at least one of the following serious criteria: fatal, life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other important medical event. TEAEs of special interest (AESI) included new/worsening graft versus host disease, graft failure or rejection, cytokine release syndrome, infusion related reactions, new/worsening pneumonitis, and progressive dyspnea. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator.
Time frame: Day 1 up to 12 months
Population: The safety population included all randomized participants who received any amount of ALVR106 or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE | 2 Participants |
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related AESI | 1 Participants |
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to death | 0 Participants |
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to study treatment discontinuation | 0 Participants |
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any SAE | 0 Participants |
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related TEAE | 2 Participants |
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related SAE | 0 Participants |
| Part A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any AESI | 1 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to death | 0 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to study treatment discontinuation | 0 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related TEAE | 1 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related AESI | 0 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any AESI | 1 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related SAE | 0 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE | 3 Participants |
| Part A ALVR106 Cohort 1: Dose A | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any SAE | 2 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to study treatment discontinuation | 0 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related SAE | 0 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE | 4 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related TEAE | 0 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to death | 1 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any SAE | 3 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any AESI | 0 Participants |
| Part A ALVR106 Cohort 2: Dose B | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related AESI | 0 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to death | 1 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE | 4 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related TEAE | 0 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any AESI | 1 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any SAE | 3 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related SAE | 0 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to study treatment discontinuation | 0 Participants |
| Part A ALVR106 Cohort 3: Dose C | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related AESI | 0 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related AESI | 0 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any AESI | 1 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related TEAE | 0 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to death | 0 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE leading to study treatment discontinuation | 0 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any SAE | 1 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any TEAE | 3 Participants |
| Part A ALVR106 Cohort 4: Dose D | Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part A) | Any treatment-related SAE | 0 Participants |
Secondary
Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A)
Viral load was measured by quantitative polymerase chain reaction (PCR) of nasal swab specimens. The cycle threshold value categorizes the concentration of viral genetic material in a participant's swab specimen, and the cycle threshold value represents the number of PCR cycles required to amplify the viral genetic material (as measured by fluorescence) to a detectable level that is distinguishable from baseline fluorescence, providing an estimate of viral load. Lower cycle threshold values indicate higher viral load and high values indicate lower viral load. A positive change from baseline indicates a decrease in the viral load. The baseline measurement was from a pre-dose nasal swab.
Time frame: Baseline and Day 28
Population: The modified intent-to-treat population included all randomized participants who received any amount of ALVR106 or placebo and had confirmed virologic infection of interest at baseline (detectable viral load). Participants with baseline and Day 28 available data are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A) | 8.60 cycles | — |
| Part A ALVR106 Cohort 1: Dose A | Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A) | 4.40 cycles | — |
| Part A ALVR106 Cohort 2: Dose B | Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A) | 8.43 cycles | Standard Deviation 6.118 |
| Part A ALVR106 Cohort 3: Dose C | Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A) | 5.78 cycles | Standard Deviation 4.696 |
| Part A ALVR106 Cohort 4: Dose D | Change in Viral Load Cycle Threshold From Baseline to Day 28 (Part A) | 7.47 cycles | Standard Deviation 7.551 |
Secondary
Identify the Recommended Phase 2 Dose (RP2D) (Part A)
The RP2D was to be determined after the maximum tolerated dose was reached in Part A.
Time frame: Day 1 up to 12 months
Population: All randomized participants who received ALVR106 in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Placebo | Identify the Recommended Phase 2 Dose (RP2D) (Part A) | NA x 10^5 cells/kg |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Part B)
Time frame: Day 1 up to 12 months
Population: No participants were enrolled into Part B due to the early termination of the study.
Secondary
Percentage Reduction in Viral Load From Baseline to Month 6 (Part B)
Time frame: Day 1 and Month 6
Population: No participants were enrolled into Part B due to the early termination of the study.