Adenovirus Infection, BK Virus Infection, Cytomegalovirus Infections, Epstein-Barr Virus Infections, Human Herpes Virus-6 Infection, JC Virus Infection
Conditions
Keywords
Allogeneic Hematopoietic Cell Transplant, Posoleucel, ALVR105, Viralym-M
Brief summary
This is a Phase 2 study to evaluate posoleucel (ALVR105, formerly Viralym-M); an allogeneic, off-the-shelf multi-virus specific T cell therapy that targets six viral pathogens: BK virus, cytomegalovirus, adenovirus, Epstein-Barr virus, human herpesvirus 6 and JC virus.
Detailed description
This is a Phase 2/3, multicenter, randomized, double-blind, placebo controlled trial comparing posoleucel to placebo for the prevention of infection or disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV in high-risk adult and pediatric patients after allogeneic HCT. There are 2 parts to the study, an open label Phase 2 cohort described in this posting, and a randomized, placebo controlled Phase 3 cohort described in NCT05305040. In the Phase 2 part, 25 to 35 eligible allogeneic HCT recipients will be enrolled and will receive 7 doses of posoleucel over 12 weeks, followed by a 14 week follow-up period.
Interventions
BIOLOGICALPosoleucel (ALVR105)
Administered as 2-4 milliliter infusion
Sponsors
AlloVir
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * ≥1 year of age at the day of screening visit. * Either no evidence of viral infection or viremia, or asymptomatic, viral infection with 3 or fewer viruses of interest at time of screening * Within 15 and 42 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment * Meet one or more of the following criteria at the time of randomization: * Related (sibling) donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B or -DR * Haploidentical donor * Unrelated donor with at least one mismatch at one of these HLA-gene loci: HLA-A, -B, -C, or -DR * Use of umbilical cord blood as stem cell source * Ex vivo graft manipulation resulting in T cell depletion * Lymphocyte Count \<180/mm3 and/or cluster of differentiation 4 (CD4) Count \<50/mm3 Key
Exclusion criteria
* History of AdV, BKV, CMV, EBV, HHV-6, and/or JCV end-organ disease within 6 months prior to randomization * Evidence of active Grade \>2 acute GVHD * Presence of non-minor uncontrolled or progressive bacterial, viral or fungal infections * Known history or current (suspected) diagnosis of CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies * Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose \>0.5 mg/kg/day) within 24 hours prior to dosing * Relapse of primary malignancy other than minimal residual disease Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease | Through Week 14 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV through Week 14 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Adenovirus (AdV) | Through Week 26 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26). |
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to BKV | Through Week 26 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 14 and Week 26 (6 endpoints each at Week 14 and Week 26). |
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Cytomegalovirus (CMV) | Through Week 26 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26). |
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease | Through Week 26 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV through Week 26. |
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Human Herpes Virus 6 (HHV-6) | Through Week 26 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26). |
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to John Cunningham Virus (JCV) | Through Week 26 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26). |
| Rates of Overall and Non-Relapse Mortality | Through Week 52 | The number of mortality events due to non-relapse causes through Week 52. |
| Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Epstein-Barr Virus (EBV) | through Week 26 | The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Posoleucel (ALVR105) Posoleucel (ALVR105): Administered as 2-4 milliliter infusion | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Posoleucel (ALVR105) |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 59.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 26 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 14 Participants |
| Type of Transplant Haploidentical | 12 Participants |
| Type of Transplant Matched Unrelated | 4 Participants |
| Type of Transplant Mismatched Unrelated | 9 Participants |
| Type of Transplant Umbilical Cord Blood | 1 Participants |
| Underlying Disease Leukemia | 17 Participants |
| Underlying Disease Lymphoma | 2 Participants |
| Underlying Disease Myelodysplasia/Myeloproliferative | 3 Participants |
| Underlying Disease Other | 2 Participants |
| Underlying Disease Sickle Cell Anemia | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 26 |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 19 / 26 |
Outcome results
Primary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV through Week 14
Time frame: Through Week 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease | 3 Participants |
Secondary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV through Week 26.
Time frame: Through Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease | 7 Participants |
Secondary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Adenovirus (AdV)
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).
Time frame: Through Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Adenovirus (AdV) | 1 Participants |
Secondary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to BKV
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 14 and Week 26 (6 endpoints each at Week 14 and Week 26).
Time frame: Through Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to BKV | 0 Participants |
Secondary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Cytomegalovirus (CMV)
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).
Time frame: Through Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Cytomegalovirus (CMV) | 5 Participants |
Secondary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Epstein-Barr Virus (EBV)
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).
Time frame: through Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Epstein-Barr Virus (EBV) | 1 Participants |
Secondary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Human Herpes Virus 6 (HHV-6)
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).
Time frame: Through Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to Human Herpes Virus 6 (HHV-6) | 0 Participants |
Secondary
Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to John Cunningham Virus (JCV)
The number of participants experiencing clinically significant infections or episodes of end-organ disease due to AdV, BKV, CMV, EBV, HHV-6, or JCV from each individual virus through Week 26 (6 endpoints each at Week 26).
Time frame: Through Week 26
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posoleucel (ALVR105) | Number of Participants Experiencing Clinically Significant Infections or Episodes of End-organ Disease Due to John Cunningham Virus (JCV) | 0 Participants |
Secondary
Rates of Overall and Non-Relapse Mortality
The number of mortality events due to non-relapse causes through Week 52.
Time frame: Through Week 52
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Posoleucel (ALVR105) | Rates of Overall and Non-Relapse Mortality | Non-Relapse Mortality | 0 Participants |
| Posoleucel (ALVR105) | Rates of Overall and Non-Relapse Mortality | Overall Mortality | 4 Participants |