BK Virus Infection, BK Virus Nephropathy
Conditions
Brief summary
The purpose of this study is to compare Posoleucel (formerly known as ALVR105; Viralym-M) to placebo in kidney transplant recipients who have high or low levels of BK virus in their blood.
Interventions
BIOLOGICALPosoleucel (formerly known as ALVR105) cells
Infusion
BIOLOGICALPlacebo (visually identical to Posoleucel)
Infusion
Sponsors
AlloVir
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who had a kidney transplant performed greater than or equal to 28 days prior to enrollment * At least 1 identified, suitably matched Posoleucel (ALVR105) cell line for infusion is available. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol. * Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion criteria
* Undergone allogeneic hematopoietic cell transplantation * Evidence or history of graft versus host disease (GVHD) or cytokine release syndrome (CRS). * Uncontrolled or progressive bacterial or fungal infections * Known or presumed pneumonia * Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose \>0.5 mg/kg/day or equivalent). * Pregnant or lactating or planning to become pregnant. * Weight \<40 kg. * Patients who received, or planned to receive abatacept or belatacept, within 3 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | Day 1 to Week 24 | An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs are defined as AEs with a start date and time on or after the first dose of study treatment through the end of study. Clinically significant changes in vital signs, physical exams, laboratory assessments and electrocardiograms were also reported as TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in BK Viral Load | Baseline and Week 24 | BK viral load was quantitated using polymerase chain reaction assays at the central laboratory. A negative change from baseline represents a reduction in BK viral load. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 26 sites in the United States between March 2021 and October 2022.
Pre-assignment details
A total of 82 participants were screened during a 2-week screening period, of which 61 were randomized and received treatment.
Participants by arm
| Arm | Count |
|---|---|
| PSL Group 1 Participants received PSL at a dose of 4 × 10\^7 cells as a slow push IV infusion once per week for 3 weeks, then once every 14 days during the 12-week dosing period (8 total doses of PSL). Participants continued to be observed for a 12-week follow-up. | 20 |
| PSL Group 2 Participants received PSL at a dose of 4 × 10\^7 cells as a slow push IV infusion once per week for 3 weeks, then once every 28 days during the 12-week dosing period (5 total doses of PSL). Participants continued to be observed for a 12-week follow-up. | 22 |
| Placebo Participants received placebo matching PSL as a slow push IV infusion once per week for 3 weeks, then once every 14 days during the 12-week dosing period (8 total doses of placebo). Participants continued to be observed for a 12-week follow-up. | 19 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Other | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | PSL Group 2 | Placebo | PSL Group 1 |
|---|---|---|---|---|
| Age, Continuous | 58.0 years | 54.0 years | 59.0 years | 59.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 5 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 17 Participants | 17 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 3 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants | 9 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 29 Participants | 7 Participants | 10 Participants | 12 Participants |
| Region of Enrollment United States | 61 participants | 22 participants | 19 participants | 20 participants |
| Sex: Female, Male Female | 12 Participants | 5 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 49 Participants | 17 Participants | 15 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 22 | 0 / 19 |
| other Total, other adverse events | 16 / 20 | 16 / 22 | 16 / 19 |
| serious Total, serious adverse events | 2 / 20 | 2 / 22 | 0 / 19 |
Outcome results
Primary
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs are defined as AEs with a start date and time on or after the first dose of study treatment through the end of study. Clinically significant changes in vital signs, physical exams, laboratory assessments and electrocardiograms were also reported as TEAEs.
Time frame: Day 1 to Week 24
Population: Safety Population: Included all participants who received any amount of PSL or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PSL Group 1 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 17 Participants |
| PSL Group 2 | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 17 Participants |
| Placebo | Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) | 16 Participants |
Secondary
Change From Baseline in BK Viral Load
BK viral load was quantitated using polymerase chain reaction assays at the central laboratory. A negative change from baseline represents a reduction in BK viral load.
Time frame: Baseline and Week 24
Population: ITT Population: Included all randomized participant with Week 24 BK viral load data available.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PSL Group 1 | Change From Baseline in BK Viral Load | -0.830 log10 copies/mL |
| PSL Group 2 | Change From Baseline in BK Viral Load | -0.520 log10 copies/mL |
| Placebo | Change From Baseline in BK Viral Load | -0.330 log10 copies/mL |