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, ALVR105, Posoleucel, Viralym-M, Virus-specific T cells (VSTs), Cytotoxic T Lymphocytes (CTLs)
Brief summary
This is a Phase 3 study to evaluate posoleucel (ALVR105, 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, a Phase 3 randomized study cohort described in this posting, and an open label Phase 2 cohort described in NCT04693637, which has completed enrollment. In this Phase 3 part, approximately 302 eligible allogeneic HCT recipients will be enrolled and will receive 7 doses of posoleucel or placebo over 12 weeks, followed by a 12 week follow-up period.
Interventions
BIOLOGICALPosoleucel (ALVR105)
Administered as 2-4 milliliter infusion, visually identical to placebo
BIOLOGICALPlacebo
Administered as 2-4 milliliter infusion, visually identical to Posoleucel (ALVR105)
Sponsors
AlloVir
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Any age at the day of screening visit. * No known or suspected clinically significant disease from AdV, BKV, CMV, EBV, HHV-6, and/or JCV * Within 25 days of receiving a first allogeneic HCT and have demonstrated clinical engraftment at time of dosing * 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 * Matched or Mismatched unrelated donor * Use of umbilical cord blood as stem cell source * Ex vivo graft manipulation resulting in T cell depletion * Received anti-thymocyte globulin or alemtuzumab (Campath-1H) 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 Grade ≥3 CRS requiring treatment associated with the administration of peptides, proteins, and/or antibodies * Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose \>1.0 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 |
|---|---|---|
| Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 14 | Through Week 14 | The average number of clinically significant infections or episodes of end-organ disease per participant due to Adenovirus (AdV), BK virus (BKV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human herpes virus 6 (HHV-6), or JC virus (JCV). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 26 | Through Week 26 | The number of clinically significant infections or episodes of end-organ disease per participant due to AdV, BKV, CMV, EBV, HHV-6, or JCV. |
| Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | Through Week 14 | The number of participants with clinically significant infections or episodes of end-organ disease due to each of the following viruses: AdV, BKV, CMV, EBV, HHV-6, or JCV. |
Countries
Australia, Belgium, Canada, France, Italy, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants at high risk for viral infection after allogeneic Hematopoietic Cell Transplant were enrolled in the Phase 3 portion of study P-105-202 between Mar 2022 and Jan 2024. The Phase 3 study was discontinued in Dec 2023 after futility analysis of the Primary Outcome Measure. No safety concerns were identified. The Phase 2 portion of study P-105-202 is reported under NCT number NCT04693637.
Pre-assignment details
A total of 451 participants were enrolled in this Phase 3 study. Due to the early termination of this study, 74 were not dosed. The 377 randomized participants that were dosed comprise the Safety Population.
Participants by arm
| Arm | Count |
|---|---|
| Posoleucel (ALVR105) Participants received posoleucel administered as 2-4 mL IV infusion once every 14 days for 7 doses. | 188 |
| Placebo Participants received placebo administered as 2-4 mL IV infusion once every 14 days for 7 doses. | 189 |
| Total | 377 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | COVID-19 Reasons | 1 | 0 |
| Overall Study | Death | 14 | 13 |
| Overall Study | Graft versus host disease | 2 | 0 |
| Overall Study | Investigator's Decision | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Not Dosed | 37 | 37 |
| Overall Study | Other | 13 | 10 |
| Overall Study | Primary Malignancy Relapse | 3 | 4 |
| Overall Study | Study Closure | 34 | 46 |
| Overall Study | Withdrawal by Subject | 15 | 10 |
Baseline characteristics
| Characteristic | Placebo | Total | Posoleucel (ALVR105) |
|---|---|---|---|
| Age, Continuous | 53.0 years | 54.0 years | 55.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 37 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 144 Participants | 287 Participants | 143 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 21 Participants | 53 Participants | 32 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants | 46 Participants | 25 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 12 Participants | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 17 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown | 22 Participants | 49 Participants | 27 Participants |
| Race/Ethnicity, Customized White | 131 Participants | 249 Participants | 118 Participants |
| Sex: Female, Male Female | 66 Participants | 144 Participants | 78 Participants |
| Sex: Female, Male Male | 123 Participants | 233 Participants | 110 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 18 / 188 | 19 / 189 |
| other Total, other adverse events | 180 / 188 | 184 / 189 |
| serious Total, serious adverse events | 88 / 188 | 86 / 189 |
Outcome results
Primary
Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 14
The average number of clinically significant infections or episodes of end-organ disease per participant due to Adenovirus (AdV), BK virus (BKV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human herpes virus 6 (HHV-6), or JC virus (JCV).
Time frame: Through Week 14
Population: Includes modified Intent-to-Treat (mITT) Population comprised of all randomized participants who received study drug and completed through Week 14 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Posoleucel (ALVR105) | Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 14 | 0.2 Infections/Episodes per participant | Standard Deviation 0.44 |
| Placebo | Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 14 | 0.2 Infections/Episodes per participant | Standard Deviation 0.42 |
p-value: 0.560395% CI: [-0.09, 0.1]ANCOVA
Secondary
Average Number of Clinically Significant Infections or Episodes of End-Organ Disease Through Week 26
The number of clinically significant infections or episodes of end-organ disease per participant due to AdV, BKV, CMV, EBV, HHV-6, or JCV.
Time frame: Through Week 26
Population: Data not collected due to early termination after DSMB futility analysis concluded the study was unlikely to meet its primary endpoint.
Secondary
Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus
The number of participants with clinically significant infections or episodes of end-organ disease due to each of the following viruses: AdV, BKV, CMV, EBV, HHV-6, or JCV.
Time frame: Through Week 14
Population: Includes mITT Population comprised of all randomized participants who received study drug and completed through Week 14 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Posoleucel (ALVR105) | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | AdV | 3 participants |
| Posoleucel (ALVR105) | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | BKV | 2 participants |
| Posoleucel (ALVR105) | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | CMV | 16 participants |
| Posoleucel (ALVR105) | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | EBV | 10 participants |
| Posoleucel (ALVR105) | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | HHV-6 | 0 participants |
| Posoleucel (ALVR105) | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | JCV | 0 participants |
| Placebo | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | HHV-6 | 0 participants |
| Placebo | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | AdV | 2 participants |
| Placebo | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | EBV | 6 participants |
| Placebo | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | BKV | 2 participants |
| Placebo | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | JCV | 0 participants |
| Placebo | Number of Participants With Clinically Significant Infections or Episodes of End-Organ Disease Due to Each Virus | CMV | 19 participants |