Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M (ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplant (HCT)
Phase: PHASE3
Conditions: BK Virus Infection, Hemorrhagic Cystitis
Sponsor: AlloVir

Protocol Number:  AVM-003-HC 
 
Official Title:     Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M 
(ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After 
Allogeneic Hematopoietic Cell Transplant 
 
NCT Number: NCT04390113 
 
Document Date:  23 February 2022 

 
 
 
 
CLINICAL STUDY PROTOCOL 
 
Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of 
Viralym-M (ALVR105) for the Treatment of Patients With 
Virus-Associated Hemorrhagic Cystitis After Allogeneic 
Hematopoietic Cell Transplant 
Investigational Product: Posoleucel (PSL, ALVR105; formerly ALVR-105, Viralym-M) 
Protocol Number: AVM-003-HC 
IND Number: 15092 
EudraCT Number: 2020-000722-26 
 
 
Sponsor: 
AlloVir, Inc. 
Kirby Grove 
2925 Richmond Avenue, Suite 1200 
Houston, TX 77098 
United States 
Telephone: 936-662-3626 
Fax: 979-289-7437 
 
Version Number: 5.0 
Original Protocol: 26 December 2019 
Amendment 1: 12 March 2020 
Amendment 2: 12 November 2020 
Amendment 3: 17 June 2021  
Amendment 4: 23 February 2022 
 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written 
consent of AlloVir, Inc. (AlloVir) except to the extent that disclosure would be required by law 
and for the purpose of evaluating and/or conducting a clinical study for AlloVir. You are allowed 
to disclose the contents of this document only to your Institutional Review Board or Independent 
Ethics Committee and study personnel directly involved with conducting this protocol. Persons 
to whom the information is disclosed must be informed that the information is confidential and 
proprietary to AlloVir and that it may not be further disclosed to third parties. 

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INVESTIGATOR AGREEMENT 
By signing below, I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary details 
for carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within 
the time designated. I will provide copies of this protocol and access to all information furnished 
by AlloVir, Inc. (AlloVir) to study personnel under my supervision. I will discuss this material 
with them to ensure they are fully informed about the study product and study procedures. I will 
let them know that this information is confidential and proprietary to AlloVir and that it may not 
be further disclosed to third parties. I understand that the study may be terminated or enrollment 
suspended at any time by AlloVir, with or without cause, or by me if it becomes necessary to 
protect the best interests of the study patients. 
I agree to conduct this study in full accordance with Food and Drug Administration Regulations, 
Institutional Review Board/Ethic Committee Regulations, and International Council for 
Harmonisation Guidelines for Good Clinical Practices. 
 
 
 
 
 
 
______________________________________________  
____________________ 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
______________________________________________ 
Investigator’s Printed Name 
 

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SYNOPSIS 
TITLE:  Phase 3 Multicenter, Double-Blind, Placebo-Controlled Trial of Viralym-M 
(ALVR105) for the Treatment of Patients With Virus-Associated Hemorrhagic Cystitis After 
Allogeneic Hematopoietic Cell Transplant  
PROTOCOL NUMBER: AVM-003-HC 
IND NUMBER: 15092 
EUDRACT NUMBER: 2020-000722-26 
INVESTIGATIONAL PRODUCT: Posoleucel (PSL, ALVR105; formerly ALVR-105, 
Viralym-M) 
PHASE: 3 
OBJECTIVES: 
The primary objective is to compare the time to resolution of macroscopic hematuria in recipients 
of posoleucel (PSL) to that in recipients of placebo.  
The key secondary objective is to compare the time to resolution of bladder pain as measured by 
Clinical Outcome Assessments (COAs) in recipients of PSL to that in recipients of placebo.  
Other secondary objectives include comparisons of the following in recipients of PSL and 
recipients of placebo: 
• To assess number of days in the hospital (for any reason including hemorrhagic cystitis [HC]) 
over the 24-week study period. 
• To assess the incidence and severity of acute graft versus host disease (GVHD) and cytokine 
release syndrome (CRS) over the 24-week study period. 
• To assess time to resolution of viremia for all target viruses over the 24-week study period 
(only for participants with detectable viremia at baseline). 
• To assess average daily bladder pain (11-point numeric rating scale [NRS]) over the 6-
week period from randomization. 
POPULATION: 
Inclusion Criteria 
Participants must meet all of the following criteria in order to be eligible to participate in the 
study: 
1. Male or female of any age, but enrollment of participants <1 year of age at the time of 
informed consent will occur only once preliminary safety data are available from 
5 participants ≥1 and <6 years of age. See Section 3.3 for details.  

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2. Had an allogeneic hematopoietic cell transplant (HCT) performed ≥21 days and ≤1 year prior 
to randomization. 
3. Myeloid engraftment confirmed, defined as an absolute neutrophil count 500/mm3 for 
3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm3 
at the time of randomization. Platelet transfusions are permitted.  
4. Diagnosed with HC based on meeting all of the following criteria: 
a. Clinical signs and/or symptoms of cystitis, such as dysuria, urinary frequency, urinary 
urgency, lower abdominal pain or tenderness, and/or bladder pain, tenderness, or 
spasms. 
b. Bedi Grade 3 hematuria, defined as macroscopic hematuria with visible clots. 
c. Viruria with ≥1 target virus (ie, BK virus [BKV], adenovirus [AdV], cytomegalovirus 
[CMV], human herpesvirus 6 [HHV-6], JC virus [JCV], and/or Epstein-Barr virus 
[EBV]). Randomization of participant may be based on viruria data obtained from 
either the local or central laboratory. 
5. At least 1 identified, suitably matched PSL cell line for infusion is available.  
6. Willing and able to provide written informed consent to participate in the study, or a parent 
or legal guardian is willing and able to provide written informed consent and the potential 
pediatric patient is able to provide assent in a manner approved by the Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) and local regulations. 
7. Women of childbearing potential (WOCBP) and men whose sexual partners are WOCBP 
must agree to use contraception during the study and for a minimum of 90 days after study 
treatment as detailed in Appendix H; participants must also refrain from donating sperm or 
eggs during the study and for at least 90 days after treatment completion. 
8. Has a negative serum pregnancy test for female participants of childbearing potential. 
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from participation in the 
study: 
1. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose 
>0.5 mg/kg/day or equivalent). 
2. Therapy 
with 
antithymocyte 
globulin, 
alemtuzumab 
(Campath-1H), 
or 
other 
immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization. 
3. Evidence of active Grade >2 acute GVHD (see Appendix E for acute GVHD grading). 
4. Uncontrolled or progressive bacterial or fungal infections (ie, evidence of bacteremia, 
fungemia, dissemination, and/or organ-specific infection not well controlled by present 
therapies). 
5. Uncontrolled or progressive viral infections (ie, evidence of viremia, dissemination, and/or 
organ-specific infection not well controlled by present therapies) not targeted by PSL. 
6. Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder. 

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7. Known or presumed pneumonia secondary to any organism that is not considered to be 
well-controlled by antimicrobial therapy (ie, clinically stable for ≥7 days on a stable 
antimicrobial regimen). 
8. Donor lymphocyte infusion performed ≤21 days before randomization. 
9. Hemodynamic or respiratory instability defined as either of the following: 
a. Requirement for continuous infusions of inotropes or vasopressors for blood pressure 
support. 
b. Requirement for endotracheal intubation or mechanical ventilation. 
10. Hemoglobin <7 g/dL despite red blood cell (RBC) transfusions. 
11. Clinically significant coagulopathy that, based upon the assessment of the Investigator, could 
result in an increased risk of active bleeding not attributed to hemorrhagic cystitis. 
12. Ongoing use of systemic anticoagulant drugs or antiplatelet drugs. 
13. Evidence of active hepatic sinusoidal obstruction syndrome. 
14. Liver dysfunction, defined as liver transaminases (ie, aspartate aminotransferase or alanine 
aminotransferase) >5 × upper limit of normal (ULN) or direct bilirubin >3 × ULN unless the 
participant has a chronic and stable diagnosis that accounts for the abnormality(ies) and 
eligibility is approved by the AlloVir Medical Monitor. 
15. Requiring renal replacement therapy ≤7 days prior to randomization.  
16. Evidence of encephalopathy. 
17. Relapse of primary malignancy. 
18. Receipt of other investigational antiviral treatments (eg, brincidofovir) ≤7 days prior to 
randomization. 
19. Pregnant, lactating, or planning to become pregnant. 
20. History of severe (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≥3) 
allergy to any component of PSL (including human serum albumin and dimethyl sulfoxide) 
or history of severe (CTCAE Grade ≥3) prior reactions to blood product transfusions. 
21. Any condition that, in the opinion of the Investigator, would compromise the safety of the 
participant, prevent study participation, or interfere with the evaluation of study endpoints. 
STUDY DESIGN AND DURATION: 
This is a Phase 3, multicenter, double-blind, placebo-controlled study to assess the efficacy and 
safety of PSL compared to placebo for the treatment of participants with virus-associated HC 
following allogeneic HCT. 
The study hypothesis is that the administration of PSL to participants with virus-associated HC 
will demonstrate superiority for the time to resolution of HC (as measured by resolution of 
macroscopic hematuria) compared to participants treated with placebo. The primary hypothesis 
will be tested in participants with BKV viruria to demonstrate superiority over placebo in this 
population (BK Intent-to-Treat [ITT] Population). A supplementary analysis will be conducted 

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in all participants with any virus-associated HC (BKV, AdV, CMV, HHV-6, JCV, and/or EBV) 
in order to evaluate efficacy in this broader population (ITT Population). 
Participants who meet all of the inclusion criteria and none of the exclusion criteria will be 
randomized in a 
 ratio to receive  sequential infusions of PSL or placebo and will be 
monitored for resolution of macroscopic hematuria as defined by the primary endpoint. 
Randomization will be stratified by 
 
. 
In the dosing strategy being evaluated in this study, all participants will receive
 infusions of 
either PSL or placebo separated by 
 (±3) days.  
The specific PSL cell line for infusion will be selected using an electronic-based software system 
(CytoMatch) that 
 
. Cryopreservation media 
(without cells) will serve as the placebo and will be identical in volume and appearance to PSL. 
All randomized participants will undergo regular visual assessments of freshly collected urine 
samples for: 1) the presence or absence of visible blood, and 2) the presence or absence of blood 
clots. The schedule of assessments for each participant will be determined by the treatment 
location (inpatient vs outpatient), time on study (through the end of Week 6 [Day 42] vs after 
Week 6), and status of macroscopic hematuria (unresolved vs resolved), as shown in Table 1. 
Each time that a participant undergoes a urine visual assessment for Bedi grading, the same 
sample should be sent for urinalysis. 
Table 1. 
Timing of Visual Urine Assessments with Urinalysis 
Treatment 
Location 
Macroscopic 
Hematuria [1] 
Time on Study 
Through the End of 
Week 6 (Day 42) 
After Week 6 (Day 43) 
Inpatient 
Unresolved 
Bedi assessment with U/A 
3 × per week 
Bedi assessment with U/A 
2 × per week ≥2 days 
apart 
Resolved 
Bedi assessment with U/A 
1 × per week 
Bedi assessment with U/A 
1 × per week 
Outpatient 
Unresolved 
Hemostick daily; 
Bedi assessment with U/A 
1 × per week  
Hemostick 2 × per week 
≥2 days apart;  
Bedi assessment with U/A 
1× per week  
Resolved 
Hemostick 1× per week; 
Bedi assessment with U/A 
1 × per week 
Hemostick 1 × per week; 
Bedi assessment with U/A 
at Week 12 and 24 study 
visits 
[1] Resolved macroscopic hematuria is defined as resolution to Grade 0 or 1 on the Bedi scale as assessed by an 
HCP on the study team on 2 consecutive visual urine assessments ≥2 days apart without continuous bladder 
irrigation or nephrostomy tubes. However, if a participant has nephrostomy tubes that are capped, Bedi assessments 
may be performed, including for the purpose of assessing for resolution. 

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Abbreviations: HCP = healthcare provider; U/A = urinalysis 
In support of the key secondary objective, bladder pain will be assessed using age-appropriate 
COAs. 
Participants will also have urine and blood samples sent at prespecified intervals during the study 
to monitor viral loads of all the viruses targeted by PSL (BKV, AdV, CMV, HHV-6, JCV, and 
EBV). For participants who develop symptoms and/or signs of possible virus-associated 
gastrointestinal disease, and whose treating physician determines that laboratory evaluation of 
stool specimens for diagnostic and/or monitoring reasons is clinically indicated, stool samples 
for AdV and CMV viral load determination should, when possible, be sent to the central 
laboratory. Similarly, for participants who develop symptoms and/or signs of possible 
virus-associated neurological disease, and whose treating physician determines that laboratory 
evaluation of cerebrospinal fluid (CSF) for diagnostic and/or monitoring reasons is clinically 
indicated, CSF samples for CMV, HHV-6, and JCV viral load determination should, when 
possible, be sent to the central laboratory. In all cases, CSF samples required for routine clinical 
care of the participant take precedence over these study-related evaluations. 
Safety assessments, including chemistries, complete blood counts with differentials, and 
physical examinations, will be performed. Adverse events will be assessed. 
As GVHD is a theoretical safety concern, the incidence and severity of GVHD will be monitored 
during the study. No participants will be permitted to receive a second infusion of PSL or placebo 
if they develop worsening of GVHD (ie, relative to baseline GVHD at the time of randomization) 
at the proposed time of infusion of the second dose.  
Analgesic use will be collected daily on a medication log for inpatients (to be collected by study 
staff) and a pain medication log within the electronic patient-reported outcome (ePRO) system 
for outpatients. 
Participants will be followed on the study for 24 weeks after the participant’s first infusion with 
study treatment.  
Following consent, study site staff will review the age-appropriate COAs with the participant (or 
parent or other caregiver, as appropriate). 
An independent Data and Safety Monitoring Board will be convened for this study to routinely 
monitor participant safety and evaluate prespecified interim analyses to stop the study early for 
futility or success. 
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
Participants randomized to the PSL arm will receive 
 separate infusions of partially 
HLA -matched PSL cells (each administered via central or peripheral intravenous [IV] infusion 
over approximately  minutes as a slow push). 
The placebo arm will receive  separate IV infusions of cryopreservation media (without cells). 
The second infusion (PSL or placebo) will occur approximately 
 (±3) days after the first 
infusion. Administering the second infusion as early as feasible within this window is 
encouraged. Participants who weigh <40 kg at the time of screening will receive 
PSL cells 

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(or placebo), while participants who weigh ≥40 kg at the time of screening will receive 
 PSL cells (or placebo). 
EFFICACY VARIABLES:  
Primary Efficacy Endpoint 
The primary endpoint is the time to resolution of macroscopic hematuria in participants with 
documented BK viruria. A supplementary analysis will evaluate the time to resolution of 
macroscopic hematuria in participants with any virus-associated HC. Resolution of macroscopic 
hematuria is defined as resolution to Grade 0 or 1 on the Bedi scale as assessed by the Investigator 
on 2 consecutive visual urine assessments ≥2 days apart without continuous bladder irrigation or 
nephrostomy tubes. However, if a participant has nephrostomy tubes that are capped, Bedi 
assessments may be performed, including for the purpose of assessing for resolution. A 
healthcare provider (HCP) on the study team (including a home health provider) may perform 
the visual urine assessment, but it is the Investigator’s responsibility to determine the Bedi score. 
Grade 0 requires no detectable blood by urinalysis; Grade 1 hematuria requires confirmation of 
resolution by urinalysis results of ≤100 RBCs/high power field (HPF). Time to resolution will 
be calculated starting from the date of randomization. The second urine assessment is required 
to establish resolution, but for the calculation of time to resolution, the date of the first of these 
two visual urine assessments without macroscopic hematuria (by the Hemostick® visual scale 
for outpatients; by the Bedi scale for inpatients) will be used. Participants will be followed for 
the primary endpoint for a maximum of 24 weeks from the date of randomization. 
Definitive therapies to stop bladder bleeding, such as cystectomy, bladder vessel embolization, 
cauterization, application of fibrin “glue” preparations, or formalin instillation are permitted, but 
will be considered treatment failures for the primary endpoint of time to resolution of 
macroscopic hematuria. Participants with ongoing continuous bladder irrigation should be 
evaluated daily by the Investigator for the ability to discontinue these supportive measures.  
For participants undergoing continuous bladder irrigation, the primary endpoint (ie, time to 
resolution of macroscopic hematuria) will be measured once participants discontinue bladder 
irrigation. Bedi grading will not be performed on days on which the participant is receiving 
continuous bladder irrigation. Discontinuation of bladder irrigation will be based upon the 
participant’s clinical condition and the treating physician’s medical judgement. 
All attempts should be made to minimize procedures or manipulations prior to urine collection 
to ensure that specimens are not contaminated due to trauma. 
If, following resolution of macroscopic hematuria, recurrence is observed, a Bedi assessment 
with urinalysis will be obtained and the date of recurrence observed by the Investigator will be 
recorded. Urine obtained at the time of recurrence will also be sent for BKV, AdV, CMV, 
HHV-6, JCV, and EBV viral load determination and banking of viral deoxyribonucleic acid for 
potential genotyping. A second Bedi assessment with urinalysis will be repeated 48 to 72 hours 
after the date of recurrence observed by the Investigator. Recurrence is defined as 2 consecutive 
Bedi grades ≥2 (macroscopic hematuria). Participants with recurrence will then undergo visual 
assessment of urine and urinalysis as indicated in Table 1 for those with unresolved hematuria 
and according to the participant’s treatment location and time on study. Following resolution of 
recurrent hematuria, follow Table 1 for those with resolved hematuria. 

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Key Secondary Efficacy Endpoint 
The key secondary endpoint is the time to resolution of bladder pain as measured by 
age-appropriate COAs. Resolution of pain is defined as participants achieving a score on the 
relevant COA that does not exceed “mild pain” (ie, scores of 3 or below on the Bladder 
Pain/Interstitial Cystitis Symptom Diary [BPIC SD], 0 to 10 NRS capturing participants’ worst 
daily pain among adolescents ≥12 years of age and adults and a parallel assessment for children 
3 to 11 years of age as a score that does not exceed 2 on the Wong-Baker FACES® Pain Rating 
Scale), without use of prescription pain medications or the use of supportive bladder care.  
This endpoint will not be assessed in participants <3 years of age.  
Other Secondary Efficacy Endpoints  
Additional secondary efficacy endpoints include the following:  
• Number of days in the hospital (for any reason including, but not limited to, HC) over the 
24-week study period. 
• Time to resolution of viremia for all target viruses (ie, BKV, AdV, CMV, HHV-6, JCV, 
and/or EBV) over the 24-week study period (only for participants with detectable viremia at 
baseline). Evaluation of this endpoint will be based on viremia quantitation performed at the 
central laboratory. Resolution of viremia will be defined by the lower limits of detection of 
the assays used. 
• Average daily bladder pain (including lower abdominal pain, bladder-related pressure, and/or 
spasm pain or dysuria) over the initial 6 weeks following randomization. 
SAFETY VARIABLES: 
The safety endpoints include the following: 
• Incidence and severity of acute GVHD (secondary endpoint) 
• Incidence and severity of chronic GVHD (exploratory endpoint) 
• Incidence and severity of CRS (secondary endpoint) 
Safety assessments will also include adverse events, vital signs, 12-lead electrocardiograms 
(ECGs), physical examination findings, and clinical laboratory assessments. 
STATISTICAL ANALYSES: 
Summary statistics will be presented by treatment group. Unless otherwise stated, continuous 
variables will be summarized using the number of non-missing observations, arithmetic mean, 
standard deviation, median, minimum, and maximum values as descriptive statistics. Categorical 
variables will be summarized using the frequency count and the percentage of participants in each 
category as descriptive statistics. 
The ITT Population will include all randomized participants regardless of whether the participant 
actually receives PSL or placebo. Participants will be analyzed according to the randomized study 
treatment. 

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The BK ITT Population will include participants in the ITT Population who have BKV identified 
as the cause of their HC. The primary efficacy analysis will be based on the BK ITT Population. 
A supplementary efficacy analysis will be based on the ITT Population. 
The Modified ITT (mITT) Population will include all randomized participants who receive any 
amount of PSL or placebo. 
The BK mITT Population will include participants in the mITT Population who have BKV 
identified as the cause of their HC. A supplementary efficacy analysis will be based on the BK 
mITT Population. 
The BK Per-Protocol (PP) Population will include all participants in the BK mITT Population who 
do not have any major protocol violations deemed to impact the results, as defined in the Statistical 
Analysis Plan (SAP).  
The Safety Population will include all participants who receive any amount of PSL or placebo. 
All safety analyses will be based on the Safety Population. Participants will be analyzed according 
to the treatment actually received. 
The primary efficacy endpoint is the time to resolution of macroscopic hematuria in participants 
with documented BK viruria. Resolution of macroscopic hematuria is defined as resolution to 
Grade 0 or 1 on the Bedi scale on 2 consecutive urine assessments ≥2 days apart without 
continuous bladder irrigation or nephrostomy tubes; Grade 1 requires confirmation of resolution 
by urinalysis results of ≤100 RBCs/HPF. If a participant has nephrostomy tubes that are capped, 
Bedi assessments may be performed, including for the purpose of assessing for resolution. 
The objective is to demonstrate the superiority of PSL therapy to placebo with respect to the time 
to resolution of macroscopic hematuria. 
The primary efficacy analysis will be conducted after all participants have completed 24 weeks of 
follow up or have discontinued early from the study. At the primary analysis, the PSL group will 
be compared to the placebo group in the BK ITT Population using a stratified log-rank test based 
on the stratification factors at randomization. The study will be considered a success if the 
one-sided p-value from the stratified log-rank test comparing treatment to control is less than 
0.0147 (reduced from 0.025 due to inclusion of an interim analysis based on Pocock method).   
If the result of the analysis of the primary efficacy endpoint (ie, time to resolution of macroscopic 
hematuria) is statistically significant based on the BK ITT Population, a formal hypothesis test 
will then be conducted of this same endpoint based on the overall ITT Population. 
If the result of this analysis is also statistically significant, a formal hypothesis test will be 
conducted of the key secondary endpoint of time to resolution of bladder pain based on the BK 
ITT Population in a manner analogous to that for the primary efficacy endpoint. If the result of 
this analysis is statistically significant, a formal hypothesis test of this same endpoint will be 
conducted based on the overall ITT Population. 
If the results of the analyses of the key secondary efficacy endpoint are statistically significant for 
both the BK ITT and overall ITT Populations, a formal hypothesis test will be conducted of the 
first other secondary endpoint, number of days in the hospital, based on the BK ITT Population. 
The analysis will be performed using a linear regression model with terms for treatment and the 
stratification factors at randomization. If the result of the analysis based on the BK ITT Population 

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is statistically significant, a formal hypothesis test of this same endpoint will be conducted based 
on the overall ITT population. 
Other continuous and categorical efficacy endpoints (including secondary and exploratory 
endpoints not selected for hierarchical testing above) will be summarized descriptively by 
treatment groups using the mITT Population.  
Time-to-event endpoints will be summarized using Kaplan-Meier estimates. In addition, the 
hazard ratio along with the 95% confidence intervals for the true hazard ratio will be calculated 
using a Cox proportional hazards model with treatment, stratification factors at randomization, 
and other potentially confounding factors. 
There will be no adjustment for multiplicity in the analyses of other efficacy endpoints. 
The safety profile will be based on treatment-emergent adverse events and changes in vital signs, 
physical examinations, clinical laboratory assessments, and ECGs. All safety analyses will be 
based on the Safety Population. 
The incidence and severity of acute GVHD, chronic GVHD, and CRS and the corresponding exact 
binomial confidence intervals with 95% confidence level will be presented by treatment group. 
Interim analyses will be conducted by an independent unblinded statistician and reviewed by the 
independent DSMB. These analyses will be based on primary efficacy endpoint data for the first 
60 participants randomized in the BK ITT Population. The interim analyses will be for purposes 
of both potentially stopping early for success and for futility. Stopping for success will be based 
on the method of Pocock. If the study is not stopped based on the interim analyses, then accrual 
to the study will continue until there are 105 participants in the BK ITT Population. The futility 
stopping in this study is considered non-binding.  
SAMPLE SIZE DETERMINATION: 
Approximately 125 participants will be randomized at approximately 90 clinical sites to achieve 
105 participants in the BK ITT Population (the primary efficacy analysis population), assuming 
85% of randomized participants will be included in the BK ITT Population. Enrollment in the 
study will continue until there are 105 participants in the BK ITT Population. Participants will be 
randomized in a 
 ratio to receive PSL or placebo. Assuming the median times to resolution for 
the placebo arm and the PSL arm are, respectively, 12 weeks and 6 weeks; time to resolution 
follows an exponential distribution; 24 weeks of follow-up; use of a log-rank test; one interim 
analysis based on the method of Pocock; control of the overall Type I error rate at the one-sided 
0.025 level; 10% of participants are censored for losses to follow-up or dropout by 24 weeks; time 
to censoring follows an exponential distribution and is equivalent in the two arms, the study will 
have 83.8% power. 

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SPONSOR: 
AlloVir, Inc. 
Kirby Grove 
2925 Richmond Avenue, Suite 1200 
Houston, TX 77098 
United States 
Telephone: 936-662-3626 
Fax: 979-289-7437 

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TABLE OF CONTENTS 
Investigator Agreement ................................................................................................................... 2 
Synopsis .......................................................................................................................................... 3 
Table of Contents .......................................................................................................................... 13 
List of Tables ................................................................................................................................ 18 
List of Figures ............................................................................................................................... 19 
List of Abbreviations and Definitions of Terms ........................................................................... 20 
1 Introduction and Background Information ............................................................................. 22 
1.1 
Viral Infection Following Allogeneic Hematopoietic Cell Transplant ......................... 22 
1.2 
Adoptive Immunotherapy for Viral Infections Following Allogeneic Hematopoietic 
Cell Transplant .............................................................................................................. 22 
1.2.1 Hematopoietic Cell Donor-Derived Virus-Specific T Cells ............................. 23 
1.2.2 Third-Party Virus-Specific T Cells ................................................................... 23 
1.3 
Posoleucel ...................................................................................................................... 23 
1.3.1 Overview of Nonclinical Studies with Posoleucel ............................................ 24 
1.3.2 Overview of Clinical Studies with Other Virus-Specific T Cells ..................... 24 
1.3.2.1 Results of an Initial Phase 1 Study with Viralym-C ........................... 24 
1.3.2.2 Results of the ARMS Study with Donor-Derived Multivirus-Specific 
T Cells ................................................................................................. 24 
1.3.2.3 The CHARMS Study with Third Party-Derived Multivirus-Specific 
T Cells, Posoleucel.............................................................................. 25 
1.3.3 Summary ........................................................................................................... 25 
1.4 
Rationale ........................................................................................................................ 26 
1.5 
Risk/Benefit ................................................................................................................... 26 
1.5.1 Potential Risks ................................................................................................... 26 
1.5.2 Potential Benefits .............................................................................................. 27 
1.5.3 COVID-19 Risk Mitigation ............................................................................... 28 
2 Study Objectives ..................................................................................................................... 29 
2.1 
Primary Objective ......................................................................................................... 29 
2.2 
Secondary Objectives .................................................................................................... 29 
2.3 
Exploratory Objectives .................................................................................................. 29 
3 Study Description.................................................................................................................... 31 

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3.1 
Summary of Study Design ............................................................................................ 31 
3.2 
Data and Safety Monitoring Board ............................................................................... 32 
3.3 
Justification for the Study Design ................................................................................. 33 
4 Selection and Withdrawal of Subjects .................................................................................... 34 
4.1 
Inclusion Criteria ........................................................................................................... 34 
4.2 
Exclusion Criteria .......................................................................................................... 34 
4.3 
Withdrawal Criteria ....................................................................................................... 36 
4.3.1 Withdrawal From the Study .............................................................................. 36 
4.3.2 Discontinuation of Study Treatment ................................................................. 36 
4.4 
Pre-Screening ................................................................................................................ 37 
4.5 
Screen Failures .............................................................................................................. 37 
5 Study and Site Closure ............................................................................................................ 38 
6 Study Treatments .................................................................................................................... 39 
6.1 
Treatment Groups .......................................................................................................... 39 
6.2 
Rationale for Dosing ..................................................................................................... 39 
6.3 
Randomization and Blinding ......................................................................................... 39 
6.4 
Breaking the Blind ........................................................................................................ 39 
6.5 
Drug Supplies ................................................................................................................ 40 
6.5.1 Selection of Study Drug for the First and Second Dose and Formulation 
Packaging .......................................................................................................... 40 
6.5.2 Study Drug Preparation, Dispensing, and Administration ................................ 41 
6.5.3 Treatment Compliance ...................................................................................... 42 
6.5.4 Storage and Accountability ............................................................................... 42 
6.6 
Prior and Concomitant Medications .............................................................................. 43 
6.6.1 Prohibited Medications ..................................................................................... 43 
6.6.2 Supportive Care ................................................................................................. 43 
6.6.3 Documentation of Prior and Concomitant Medication Use .............................. 43 
7 Efficacy Assessments.............................................................................................................. 45 
7.1 
Macroscopic Hematuria Assessment ............................................................................ 46 
7.1.1 Overview ........................................................................................................... 46 
7.1.2 Hematuria Grading Using the Bedi Criteria ...................................................... 47 
7.1.3 Hemostick® Visual Scale for Outpatients ......................................................... 48 
7.1.4 Timing of Urine Visual Assessments with Urinalyses ...................................... 48 

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7.1.5 Urine Visual Assessment to Confirm Resolution of Macroscopic Hematuria .. 49 
7.1.6 Urinalysis for Quantitation of Red Blood Cells ................................................ 50 
7.1.7 Pharmacologic Agents or Foods that May Cause Urine Discoloration............. 50 
7.1.8 Handling of Participants Receiving Definitive Therapies to Stop Bladder 
Bleeding, Continuous Bladder Irrigation, or Nephrostomy Tubes ................... 50 
7.1.9 Assessments in Participants with Recurrence of Hematuria ............................. 50 
7.2 
Clinical Outcome Assessments ..................................................................................... 51 
7.2.1 Selected Items from the Bladder Pain/Interstitial Cystitis Symptom Diary ...... 52 
7.2.2 Wong-Baker FACES Pain Rating Scale ........................................................... 52 
7.2.3 PROMIS Parent Proxy Pain Behavior Short Form (8a) .................................... 52 
7.2.4 Pain Medication Log ......................................................................................... 53 
7.2.5 Urinary Frequency and Nocturia Items from the Interstitial Cystitis Symptoms 
Index 53 
7.2.6 Age-Appropriate Global Impression Scales ...................................................... 53 
7.2.7 EQ-5D-5L, EQ-5D-Y, and EQ-5D-Y Proxy Version 1 .................................... 53 
7.2.8 Planned Exit Interview ...................................................................................... 54 
7.3 
Resolution of Viral Infections ....................................................................................... 54 
8 Safety Assessments ................................................................................................................. 55 
8.1 
Adverse Events .............................................................................................................. 55 
8.1.1 Adverse (Drug) Reaction .................................................................................. 56 
8.1.2 Unexpected Adverse Drug Reaction ................................................................. 56 
8.1.3 Assessment of Adverse Events by the Investigator .......................................... 56 
8.1.4 Adverse Events of Special Interest .................................................................... 58 
8.2 
Serious Adverse Events ................................................................................................. 58 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators ................................ 59 
8.3.1 Initial Reports .................................................................................................... 59 
8.3.2 Follow-Up Reports ............................................................................................ 59 
8.4 
Pregnancy Reporting ..................................................................................................... 60 
8.5 
Expedited Reporting ...................................................................................................... 60 
8.6 
Special Situation Reports .............................................................................................. 60 
8.7 
Clinical Laboratory Evaluations .................................................................................... 61 
8.8 
Vital Signs ..................................................................................................................... 62 
8.9 
Electrocardiograms ........................................................................................................ 62 

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8.10 Physical Examinations .................................................................................................. 62 
8.11 Graft Versus Host Disease ............................................................................................ 62 
8.11.1 Acute Graft Versus Host Disease ...................................................................... 62 
8.11.2 Chronic Graft Versus Host Disease .................................................................. 62 
8.12 Cytokine Release Syndrome ......................................................................................... 63 
8.13 Post-Infusion Monitoring .............................................................................................. 63 
9 Statistical Analyses ................................................................................................................. 64 
9.1 
Analysis Populations ..................................................................................................... 64 
9.1.1 Intent-to-Treat Population ................................................................................. 64 
9.1.2 BK Intent-to-Treat Population .......................................................................... 64 
9.1.3 Modified Intent-to-Treat Population ................................................................. 64 
9.1.4 BK Modified Intent-to-Treat Population ........................................................... 64 
9.1.5 BK Per-Protocol Population .............................................................................. 64 
9.1.6 Safety Population .............................................................................................. 64 
9.2 
Statistical Methods ........................................................................................................ 64 
9.2.1 Analysis of Efficacy .......................................................................................... 65 
9.2.1.1 Primary Efficacy Endpoint Analysis .................................................. 65 
9.2.1.2 Key Secondary Efficacy Analysis ...................................................... 66 
9.2.1.3 Other Efficacy Analysis ...................................................................... 66 
9.2.2 Analysis of Safety ............................................................................................. 67 
9.2.3 Interim Analysis ................................................................................................ 67 
9.2.3.1 Interim Analysis for Stopping Early for Success ................................ 67 
9.2.3.2 Interim Analysis for Futility ............................................................... 67 
9.2.4 Sample Size Determination ............................................................................... 68 
10 Data Management and Record Keeping ................................................................................. 69 
10.1 Data Management ......................................................................................................... 69 
10.1.1 Data Handling ................................................................................................... 69 
10.1.2 Computer Systems ............................................................................................. 69 
10.1.3 Data Entry ......................................................................................................... 69 
10.1.4 Medical Information Coding ............................................................................. 69 
10.1.5 Data Validation ................................................................................................. 69 
10.2 Record Keeping ............................................................................................................. 69 

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10.3 End of Study .................................................................................................................. 70 
11 Investigator Requirements and Quality Control ..................................................................... 71 
11.1 Ethical Conduct of the Study ........................................................................................ 71 
11.2 Institutional Review Board/Independent Ethics Committee ......................................... 71 
11.2.1 Institutional Review Board ................................................................................ 71 
11.2.2 Independent Ethics Committee ......................................................................... 71 
11.3 Informed Consent .......................................................................................................... 71 
11.4 Subject Card .................................................................................................................. 72 
11.5 Study Monitoring Requirements ................................................................................... 72 
11.6 Disclosure of Data ......................................................................................................... 72 
11.7 Retention of Records ..................................................................................................... 73 
11.8 Publication Policy ......................................................................................................... 73 
11.9 Financial Disclosure ...................................................................................................... 73 
11.10 Insurance and Indemnity ............................................................................................... 73 
11.11 Legal Aspects ................................................................................................................ 73 
12 Study Administrative Information .......................................................................................... 74 
12.1 Protocol Amendments ................................................................................................... 74 
12.2 Home Health Visits ....................................................................................................... 74 
13 References ............................................................................................................................... 75 
Appendix A:  Schedule of Procedures .......................................................................................... 80 
Appendix B:  Clinical Outcome Assessments by Age Group ...................................................... 84 
Appendix C:  Blood Volume Table and Sampling Schedule ....................................................... 87 
Appendix D:  Clinical Laboratory Analytes ................................................................................. 93 
Appendix E:  Graft Versus Host Disease Scales .......................................................................... 95 
Appendix F:  Cytokine Release Syndrome Scale ......................................................................... 98 
Appendix G:  Monitoring for and Management of Cytokine Release Syndrome ........................ 99 
Appendix H:  Contraceptive Requirements ................................................................................ 101 

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LIST OF TABLES 
Table 1. 
Timing of Visual Urine Assessments with Urinalysis .................................................. 6 
Table 2. 
Timing of Visual Urine Assessments with Urinalysis ................................................ 49 
 
 
 

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LIST OF FIGURES 
Figure 1. Summary of Study Design .......................................................................................... 32 
Figure 2. Schema for Determining the Bedi Grade from Urine Visual Assessment, Laboratory 
Data, and Clinical Evaluation ..................................................................................... 48 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS  
Abbreviation 
Definition 
AdV 
Adenovirus 
AESI 
Adverse event of special interest 
BKV 
BK virus 
BPIC SD 
Bladder Pain/Interstitial Cystitis Symptom Diary 
CAR 
Chimeric antigen receptor 
CFR 
Code of Federal Regulations 
CGIC 
Caregiver Global Impression of Change 
CGIS 
Caregiver Global Impression of Severity 
CIBMTR 
Center for International Blood and Marrow Transplant Research 
CMV 
Cytomegalovirus 
COA 
Clinical Outcome Assessment 
COVID-19 
Coronavirus disease 2019 
CR 
Complete response 
CRA 
Clinical Research Associate 
CRS 
Cytokine release syndrome 
CSF 
Cerebrospinal fluid 
CTA 
Clinical trial authorisation 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTL 
Cytotoxic T lymphocyte 
DNA 
Deoxyribonucleic acid 
DSMB 
Data and Safety Monitoring Board 
EBV 
Epstein-Barr virus 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
ELIspot 
Enzyme-linked immunospot 
ePRO 
Electronic patient-reported outcome 
EQ VAS 
EQ visual analog scale 
EQ-5D 
EuroQol 5 Dimensions 
EQ-5D-5L 
EuroQol 5 Dimensions 5 Levels 
EQ-5D-Y 
EuroQol 5 Dimensions for Younger Patients 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
GVHD 
Graft versus host disease 
HC 
Hemorrhagic cystitis 
HCP 
Health Care Provider 
HCT 
Hematopoietic cell transplant 
HHV-6 
Human herpesvirus 6 
HLA 
Human leukocyte antigen 

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Abbreviation 
Definition 
HPF 
High power field 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
ICPI 
Interstitial Cystitis Problem Index 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
IL 
Interleukin 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intent-to-Treat 
IV 
Intravenous(ly) 
JCV 
JC virus 
mITT 
Modified Intent-to-Treat 
MTD 
Maximum tolerated dose 
NRS 
Numeric rating scale 
PBMC 
Peripheral blood mononuclear cell 
PGIC 
Patient Global Impression of Change 
PGIS 
Patient Global Impression of Severity 
PP 
Per-Protocol 
PR 
Partial response 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
PSL 
Posoleucel 
PTLD 
Post-transplant lymphoproliferative disease 
PVSS 
Pharmacovigilance and Safety Services  
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SRG 
Safety Reporting Group  
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TEAE 
Treatment-emergent adverse event 
U/A 
ULN 
Urinalysis 
Upper limit of normal 
USA 
Unites States of America 
VST 
Virus-specific T cell 
v/v 
Volume per volume 
WOCBP 
Women of childbearing potential  

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1 
INTRODUCTION AND BACKGROUND INFORMATION  
1.1 
Viral Infection Following Allogeneic Hematopoietic Cell Transplant 
During the period of immune recovery after allogeneic hematopoietic cell transplant (HCT), viral 
infections, which are normally controlled by T cell immunity, are an important cause of morbidity 
and mortality. Viral infections may affect any organ in the body and in HCT can often be serious 
or, depending on the virus, fatal. Amongst patients with viral infection status post-HCT, one of the 
most common serious manifestations is hemorrhagic cystitis (HC). The most common cause of 
severe viral-induced HC is BK virus (BKV), but HC has also been associated, albeit with a lower 
incidence, with viral infections from adenovirus (AdV), cytomegalovirus (CMV), human 
herpesvirus 6 (HHV-6), and JC virus (JCV).1,2,3,4 The risk for infection is dictated by a number of 
factors, including the degree of immunosuppression and the immune status of the donor. 
Reactivation of latent viruses such as BKV and CMV, or infection with a new virus such as AdV, 
has become increasingly prominent. In a recent study of infections following haplo-identical 
allogeneic HCT, 72% of patients experienced at least 1 severe viral infection.5 Fifteen percent of 
patients developed CMV infection despite prophylaxis and 19% developed BKV-associated HC. 
One out of 3 children is reported to have an AdV infection within 6 months post-allogeneic HCT.6 
Progression to AdV disease is associated with significant morbidity and mortality rates of up to 
50%.7 Similarly, in patients receiving either cord blood or T cell-depleted transplants, viral 
infections were frequent and the most common cause of death in both groups. Even among T cell 
replete transplants using the post-cyclophosphamide protocol, the incidence of viral infections was 
reported to be 70%, with BKV and CMV being the most frequent and the most clinically 
threatening etiologies.8  
The primary clinical manifestation of BKV infection following allogeneic HCT is severe HC, 
which manifests as gross hematuria and is defined by lower urinary tract symptoms that typically 
include severe, often debilitating, bladder pain (marked by use of pain medications, often requiring 
continuous narcotic infusions); bladder pressure; urinary frequency; urinary urgency; nocturia; and 
the presence of pronounced blood clots in urine that may lead to urinary retention and patient 
distress.9,10 A retrospective study demonstrated that among 2477 patients undergoing their first 
allogeneic HCT over an 8-year period, of whom 98% were transplanted for cancer, 629 patients 
(25%) developed BKV-associated HC.11 Moreover, BKV infection was associated with the 
development of kidney failure as well as increased overall mortality. 
Additionally, antiviral pharmacologic agents are only partially effective against many of the target 
viruses; their use is costly and may be associated with significant toxicities and the emergence of 
drug-resistant mutant viruses. As delays in the recovery of endogenous virus-specific T cells 
(VSTs) are clearly associated with viral reactivation and disease in these patients, cellular 
immunotherapy to restore viral-specific immunity has been investigated as a potential therapeutic 
option. 
1.2 
Adoptive Immunotherapy for Viral Infections Following Allogeneic 
Hematopoietic Cell Transplant 
The first virus to be targeted using an adoptive T cell transfer approach was CMV.12 This was 
followed by numerous studies with not only CMV-directed T cell products (eg, ex vivo expanded 
polyclonal lines, interferon [IFN] γ-captured cells, and multimer-selected products)13,14,15,16,17,18,19 
but also T cell products directed toward other viruses, including Epstein-Barr virus (EBV) and 

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AdV. These clinically implemented immunotherapeutic strategies are considered safe and are 
associated with clinical benefit.20,21,22,23,24,25,26,27,28 
1.2.1 
Hematopoietic Cell Donor-Derived Virus-Specific T Cells 
Adoptive transfer of HCT donor-derived VSTs (ie, VSTs expanded or selected from a transplant 
donor) has been successfully used to prevent and treat viral infections29, including AdV and CMV 
infections as well as drug-refractory EBV-positive lymphomas, that complicate allogeneic HCT.30  
Previous studies utilized an adoptive immunotherapeutic approach to prevent/treat BKV, AdV, 
CMV, HHV-6, and EBV-associated infections post-HCT using a multivirus-directed T cell 
product prepared using peripheral blood mononuclear cells (PBMCs) from a stem cell donor.31,32 
To generate VSTs that recognized all 5 viruses, stem cell donor PBMCs were exposed to 
overlapping peptide libraries spanning immunogenic antigens derived from each virus, followed 
by an expansion phase using media supplemented with interleukin (IL)-4 and IL-7.31,32 When these 
donor-derived VSTs were administered to 21 corresponding allogeneic HCT recipients at doses 
ranging from 0.5107 to 2107 cells/m2, the infused cells expanded in vivo and produced clinical 
responses without adverse events.25 
In summary, this study demonstrated that T cell lines having specificity for up to 5 viruses 
(including BKV, which had never been previously targeted using this therapeutic modality) could 
be generated from stem cell donors, and treatment with these VSTs was well tolerated and 
associated with clinical improvement. However, despite the successful use of various stem cell 
donor-derived VSTs over more than 20 years, there are significant limitations to this approach, 
making it unsuitable for a potential commercial product. 
1.2.2 
Third-Party Virus-Specific T Cells 
An alternative to preparing stem cell donor-derived VSTs for individual patients is to bank 
partially human leukocyte antigen (HLA)-matched allogeneic VSTs, obtained from healthy 
pre-immune third-party donors (not the stem cell donor) with demonstrated immunity to virus(es) 
that could be available as an “off-the-shelf” product for immediate use. This approach theoretically 
overcomes some of the limitations of HCT donor-derived VSTs. Specifically, patients do not have 
to wait for the cell line to be produced, and taking the multivirus approach (ie, deriving cell lines 
by antigenically stimulating against peptides from multiple viruses of interest) results in a 
ready-for-use pluripotent cell line specific for multiple viruses of interest. A potential concern with 
this approach is that the mismatched product may not persist long enough in vivo to control the 
viral infection, because the recipient may generate an immune response to the non-shared 
transplantation antigens. Despite this theoretical concern, several studies have demonstrated that 
third-party VSTs are associated with clinical benefit, including AdV, CMV, and EBV 
infections.33,34,35,36 
1.3 
Posoleucel 
AlloVir, Inc. (AlloVir) is developing posoleucel (PSL, ALVR105; formerly ALVR-105, 
Viralym-M) for the treatment of virus-associated HC. Posoleucel is a biological product consisting 
of PSL cells (third-party, multivirus-specific T cells with specificity for BKV, AdV, CMV, 
HHV-6, JCV, and EBV) in cryopreservation media comprised of 
 
. Posoleucel cells are generated from 
PBMCs collected from eligible third-party donors by exposing the PBMCs to peptides spanning 

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immunogenic antigens from BKV (large T and VP1), AdV (hexon and penton), CMV (IE1 and 
pp65), HHV-6 (U11, U14, and U90), and EBV (LMP2, EBNA1, and BZLF1). Specificity for JCV 
is achieved by the substantial homology between the BK and JC human polyomaviruses: at the 
viral genome level, their deoxyribonucleic acid (DNA) sequences are 72% identical and at the 
amino acid level, large T and VP1 are >85% homologous.37 Published preclinical38,39 and clinical40 
data provide evidence for cross-reactive recognition and antiviral activity of JCV by BK-specific 
T cells. The PSL cell lines are subsequently characterized for viral specificity by IFNγ 
enzyme-linked immunospot (ELIspot) assay. Posoleucel is cryopreserved for use as an 
“off-the-shelf” product. 
For additional information on PSL, refer to the current Investigator’s Brochure (IB). 
1.3.1 
Overview of Nonclinical Studies with Posoleucel 
Consistent with regulatory guidance, AlloVir proceeded to clinical studies following completion 
of in vitro studies. No nonclinical animal pharmacology, pharmacokinetic, or toxicology studies 
of PSL have been conducted or are planned. For additional information related to nonclinical 
studies with PSL, see the current IB. 
1.3.2 
Overview of Clinical Studies with Other Virus-Specific T Cells 
1.3.2.1 
Results of an Initial Phase 1 Study with Viralym-C 
Initially, AlloVir completed a Phase 1 study to assess the safety and efficacy of Viralym-C, a 
third-party, CMV-specific T cell product, in pediatric and adult allogeneic HCT recipients with 
refractory CMV infections.41 Similar to PSL, Viralym-C is generated from PBMCs after expansion 
in the presence of overlapping viral peptides and cytokines. Unlike PSL, Viralym-C is only 
directed against a single virus, CMV. Although Viralym-C is a single-VST product, the results of 
this study support the safety and efficacy of AlloVir’s VST products when used in a clinical setting. 
Briefly, a bank of 8 Viralym-C lines were generated from 8 carefully selected, healthy, 
seropositive, transplant donor-eligible volunteers who were predicted to provide a suitably 
matched cell line for at least 95% of potential patients. Ten participants were treated with 
Viralym-C: each participant received a single intravenous (IV) infusion of 2×107 partially 
HLA-matched VSTs/m2 with the option to receive a second infusion after 4 weeks and additional 
infusions at biweekly intervals thereafter. Of the 10 treated participants, 8 participants received a 
single infusion and 2 participants required 2 infusions for sustained benefit. There were no 
immediate infusion-related toxicities and there were no cases of de novo or recurrent graft versus 
host disease (GVHD). Based on viral load (measured by quantitative polymerase chain reaction) 
and/or resolution of signs and/or symptoms, Viralym-C appeared to control CMV infections in all 
participants with 8 complete responses (CRs) and 2 partial responses (PRs) achieved within 
4 weeks of infusion. One participant with CMV retinitis had complete resolution of disease 
following Viralym-C infusion. 
1.3.2.2 
Results of the ARMS Study with Donor-Derived Multivirus-Specific T Cells 
In order to broaden the range of viral infections targeted by VSTs, AlloVir developed 
donor-derived multivirus-specific T cells with specificity for BKV, AdV, CMV, HHV-6, and 
EBV. An initial open-label Phase 1/2 study was conducted to assess the safety and toxicity of the 
multivirus-specific T cells in participants at risk of developing BKV, AdV, CMV, HHV-6, or EBV 
infections after allogeneic HCT.25 The first stage of the study was a Phase 1 dose-escalation study 

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to evaluate the safety of 3 dose levels and to determine the maximum tolerated dose (MTD) level. 
Upon the completion of Phase 1, additional participants were to be accrued at the MTD level to 
evaluate a clinically relevant endpoint for antiviral activity in Phase 2. 
Participants received 
 donor-derived multivirus cytotoxic T lymphocytes 
 in a single infusion in the Phase 1 dose-escalation stage of the study, and 
 
multivirus CTLs
for the fixed-dose Phase 2 efficacy component (actual number of cells infused 
ranged 
 
 
 
 
 per participant). Participants who had a PR or received 
therapy post-infusion that could ablate the infused T cells were eligible to receive up to 2 additional 
doses 28 days after the first dose. Participants were followed for toxicity for 30 days, GVHD for 
6 weeks, and antiviral responses for 3 months; long-term follow-up continued for 12 months 
following the final CTL infusion. 
A total of 21 participants were enrolled, and all 21 participants completed the study. All doses 
were well tolerated. There were no adverse events experienced by participants enrolled in the study 
that were considered treatment-related. Three participants developed Stage 2 skin GVHD (Grade 1 
overall) and 1 participant developed Stage 3 skin GVHD (Grade 2 overall) in the 6-week initial 
follow-up period; all of these reactions responded to topical steroids. 
1.3.2.3 
The CHARMS Study with Third Party-Derived Multivirus-Specific T Cells, 
Posoleucel 
To investigate the safety and clinical efficacy of PSL, a multivirus-specific T cell product reactive 
with BKV, AdV, CMV, HHV-6, and EBV generated from third-party, healthy, eligible donors, a 
Phase 2 clinical study was conducted in recipients of allogeneic HCT with drug-refractory 
infections with 1 of the 5 viruses targeted by PSL.42 (For additional information on PSL, refer to 
the current IB.)  
1.3.3 
Summary 
The available data, including data from the Phase 2 CHARMS study, confirm the feasibility and 
safety of PSL administered as an “off-the-shelf” product to treat drug-refractory virus-associated 
disease. Infusion of the cells was well tolerated, including in participants who received multiple 
infusions. The infused cells expanded in vivo and were associated with meaningful clinical 
improvement in participants suffering from refractory BKV, AdV, CMV, HHV-6, and EBV 
reactivation and virus-associated disease. 
In the Phase 2 CHARMS study with PSL, approximately 25% of participants received more than 
1 cell infusion using a similar cell dose per infusion as will be used in this study.42 These additional 
infusions were administered when participants did not respond adequately to their initial cell 
infusions and were not associated with a safety or tolerability profile that was different than that 
associated with single infusions. In the current study, only severely affected HC participants 
(Grades 3 and 4) who are expected to benefit from the planned 2 sequential infusions will be 
enrolled. Given the multi-viral coverage of PSL, the 2 infusions are also expected to provide 
enhanced prophylaxis against those target viruses that may be inactive at the time of infusion, but 
to which the participants remain susceptible as their immune systems reconstitute following HCT. 
For additional information related to clinical studies with PSL, see the current IB. 

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1.4 
Rationale 
In healthy individuals, T cell immunity defends against viruses. In allogeneic HCT recipients, the 
use of potent immunosuppressive regimens (and subsequent associated immune compromise) 
leaves patients susceptible to severe viral infections. Viral infections are major causes of mortality 
and morbidity after HCT and, in general, have become the primary etiology for transplant-related 
mortality.  
There are no FDA-approved therapies for BKV infection or BKV-associated HC. Current standard 
of care is supportive, including diuresis and continuous bladder irrigation to mitigate urinary 
obstruction, antispasmodics and narcotics to alleviate suffering, hyperbaric oxygen, 
nephrostomies, and/or dialysis for acute renal failure. In some cases, a cystectomy has been 
required to control life-threatening hemorrhage caused by BKV-associated HC. The most 
frequently used antiviral drug for disease treatment is cidofovir. However, cidofovir is associated 
with nephrotoxicity and, in the absence of prospective, randomized, controlled clinical studies, its 
efficacy for the treatment of BKV-associated HC remains uncertain.  
Since recovery of VSTs after HCT results in resolution of viral infections, adoptive 
immunotherapy to decrease the time to immune reconstitution is an attractive alternative to current 
standard of care. AlloVir’s approach is to restore T cell immunity by the administration of ex vivo 
expanded, non-genetically modified VSTs to control viral infections and eliminate symptoms for 
the period until the transplant patient’s own immune system is restored. To achieve this goal, 
AlloVir has manufactured VSTs from PBMCs procured from healthy pre-screened (for infectious 
agents and disease risk factors as mandated by FDA Title 21 of the Code of Federal Regulations 
[CFR] Part 1271, subpart C) seropositive third-party donors, which are cryopreserved and 
available as a partially HLA-matched “off-the-shelf” product. Posoleucel is specific for 5 viruses 
(BKV, AdV, CMV, HHV-6, and EBV). Additional antiviral specificity for JCV is anticipated due 
to the substantial homology between the BK and JC human polyomaviruses; published preclinical 
and clinical data provide evidence for cross-reactive recognition and antiviral activity of JCV by 
BK-specific T cells.40 Since PSL is only partially matched with the recipient and donor cells, PSL 
cells are intended to circulate only until the patient regains immunocompetence following HCT 
engraftment and immune system repopulation. Therefore, PSL cells are designed to be used as an 
“immunologic bridge therapy” that provides an immunocompromised patient with T cell immunity 
until the patient engrafts and can mount an endogenous immune response.  
To date, clinical studies of PSL conducted in >50 allogeneic HCT participants with refractory 
infections have demonstrated preliminary clinical safety and efficacy (>90% positive clinical 
response [either PR or CR]) using these cryopreserved third-party T cells. 
1.5 
Risk/Benefit 
1.5.1 
Potential Risks 
Posoleucel primarily targets cells infected with BKV (and/or JCV), AdV, CMV, HHV-6, and/or 
EBV. The main risks of administration are inflammation at sites of disease and GVHD due to cross 
reactivity with alloantigens. Adverse events attributable to VST administration may potentially 
occur in a small percentage of the treated population. These can include both hematologic and 
non-hematologic effects, as reported in the CHARMS study.  

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Studies of donor-derived VSTs suggest that VSTs do not persist in patients who receive 
methylprednisolone at doses of ≥1 mg/kg/day. Therefore, if participants develop severe 
inflammatory reactions due to PSL a therapeutic option is to administer methylprednisolone (1 to 
2 mg/kg/day). Skin rashes or skin GVHD can be treated with topical steroids. 
As with other biological therapies delivered by IV infusion, possible side effects of PSL infusion 
include allergic reaction (anaphylaxis), decreased oxygenation, nausea/vomiting, arrhythmia, and 
hypertension. 
Most participants (including children) are expected to have venous access catheters in place for 
their underlying disease and HCT procedures. Since study-related collection of blood samples and 
infusion of PSL or placebo will utilize these catheters, there is minimal incremental risk posed by 
these study-related procedures. The time points and blood volumes to be collected during this 
study are provided in Appendix C. Since this study will enroll both adult and pediatric participants, 
there are different sampling schemes (and associated volumes) based on body weight. 
In order to minimize the volume of blood collected during the study, especially for pediatric 
participants, the blood volume of individual samples has been reduced to the maximum extent 
feasible, and in some cases (eg, pediatric participants weighing <20 kg) collection of blood 
samples at certain time points has been eliminated entirely (see Appendix C). This has been done 
to maintain the scientific integrity of the study while minimizing risks to participants.  
For the collection of other study-related material from participants, there are no invasive 
procedures that are required for the study conduct beyond those procedures being used for the 
routine clinical care of these participants. For example, participants with indwelling urinary 
catheters will have urine samples drawn off the catheter, but the decision to place and maintain the 
catheter should be driven by the clinical needs of the participant as determined by the treating 
physician, and not by study requirements. Similarly, procedures such as viral load assessment on 
stool or cerebrospinal fluid (CSF) specimens will only be undertaken when the clinical course of 
the participant necessitates an evaluation of stool (eg, participant develops diarrhea), or of CSF 
(eg, participant develops neurological signs and symptoms necessitating the collection and 
evaluation of CSF for clinical management purposes as determined by the participant’s treating 
physician). 
For more details regarding potential risks with PSL treatment, see the current IB. 
1.5.2 
Potential Benefits 
A serious unmet medical need exists for patients experiencing viral infections and diseases such 
as BKV-associated HC following allogeneic HCT. There are no FDA- or European Medicines 
Agency-approved antiviral therapies in this clinical context, and the antivirals that are employed 
are narrow in their antiviral spectrum, largely ineffective, and associated with significant adverse 
effects. The CHARMS study and other related clinical studies suggest that PSL is a safe and 
effective broad-spectrum approach to treat commonly observed, severe virus-associated disease 
after HCT. The results of these studies provide preliminary evidence of PSL efficacy in multiple 
opportunistic viral infections in allogeneic HCT patients, and its safety profile has the potential to 
be significantly better than that of standard, and inadequately effective, antiviral therapy. 

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1.5.3 
COVID-19 Risk Mitigation 
The trial is due to be initiated during the ongoing coronavirus disease 2019 (COVID-19) pandemic. 
The Sponsor has reviewed guidance from regulatory authorities and reports from the literature 
while planning trial start-up and conduct.43,44,45,46 The Sponsor will communicate with study sites 
before study initiation and during the conduct of the study concerning the potential impact of 
COVID-19 on study-related procedures and overall conduct. The Sponsor will continue to monitor 
COVID-19 activity in the geographic areas and institutions where the trial will be conducted and 
conduct an ongoing risk assessment throughout the trial. The risk assessment will be documented 
on an ongoing basis in the Sponsor’s trial master file. If necessary, the Sponsor will implement 
and document mitigation strategies to ensure participant safety while enabling sites to generate 
reliable data and maintain integrity of the trial and trial data. As an example, if it is necessary to 
conduct some study visits virtually or via home health visits, the Sponsor will document the 
changes made, communicate recommendations about such changes in a timely fashion to minimize 
or prevent disruptions to the trial, and support study sites in implementing these changes.  
The Sponsor has conducted a specific risk assessment for concomitant use of a COVID-19 vaccine 
with PSL.46 The Sponsor does not expect any interactions between PSL and a COVID-19 vaccine, 
but COVID-19 vaccination should be deferred for at least 28 days following the second dose of 
study treatment (PSL or placebo) when feasible to minimize confounding due to the possible 
overlap of adverse effects. Patients with overlapping treatment of PSL and a COVID-19 vaccine 
within 28 days of one another will be kept on-study and monitored as usual for safety, as defined 
in Section 8. 

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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective is to compare the time to resolution of macroscopic hematuria in recipients 
of PSL to that in recipients of placebo.  
2.2 
Secondary Objectives 
The key secondary objective is to compare the time to resolution of bladder pain as measured by 
Clinical Outcome Assessments (COAs) in recipients of PSL to that in recipients of placebo.  
Other secondary objectives include comparisons of the following in recipients of PSL and 
recipients of placebo: 
• To assess number of days in the hospital (for any reason including HC) over the 24-week study 
period. 
• To assess the incidence and severity of acute GVHD and cytokine release syndrome (CRS) 
over the 24-week study period. 
• To assess time to resolution of viremia for all target viruses over the 24-week study period 
(only for participants with detectable viremia at baseline). 
• To assess average daily bladder pain (11-point numeric rating scale [NRS]) over the 6-week 
period from randomization.  
2.3 
Exploratory Objectives 
The exploratory objectives include comparisons of the following in recipients of PSL and 
recipients of placebo as measured over the 24-week study period: 
• Cumulative days and time to discontinuation of supportive therapy for HC, including IV 
hydration, continuous bladder irrigation, and/or nephrostomy tube placement. 
• Incidence and time to resolution of HC-associated signs and symptoms other than bladder pain. 
• Incidence and time to recurrence of HC-associated signs and symptoms, including bladder 
pain, bladder pressure, spasms, urinary frequency, urinary urgency, nocturia, dysuria, and/or 
the presence of blood clots in urine. 
• Requiring red blood cell (RBC) and/or platelet transfusions and the number of required RBC 
and/or platelet transfusions (measured in transfusion units/participant). 
• Change in renal function as assessed by estimated glomerular filtration rate (eGFR). For 
participants requiring dialysis, number of days on dialysis will be captured. 
• Time to resolution of BK viruria. Resolution of viruria will be defined by the lower limits of 
detection of the assay used. 
• Resolution of macroscopic hematuria as assessed at Weeks 2, 4, 6, 8, and 12 after 
randomization. 
• Level of pain as assessed at Weeks 2, 4, 6, 8, and 12 after randomization. 
 

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• Time to resolution of non-BK target viral infections (ie, associated signs, symptoms, and 
presence/absence of viral load in blood and/or urine for AdV, CMV, HHV-6, JCV, and/or 
EBV) present at the time of randomization. Peripheral blood and, where relevant, urine 
(ie, evidence of virus in the urine at baseline), will be monitored for AdV, CMV, HHV-6, JCV, 
and/or EBV viral load. 
• Incidence of target viral reinfections (ie, BKV, AdV, CMV, HHV-6, JCV, and/or EBV) as 
defined by new onset viremia or viruria and the presence of associated symptoms relative to 
baseline. 
• Length of use of IV narcotic medication(s) for control of lower abdominal/bladder pain.  
• Length of use of any pain medication(s) (IV, oral, or both), including antispasmodics used for 
pain, for control of lower abdominal/bladder pain.  
• Length of use of immunosuppressive agents, by specific agent used (including dose and 
changes in dose). 
• Number of hospitalizations/re-hospitalizations for any reason. 
• Cumulative incidence and severity of chronic GVHD. 
• Incidence and duration of use of other antiviral therapies (eg, ganciclovir, valganciclovir, 
foscarnet). 
• Overall survival, defined as time to death (from any cause) from the time of randomization in 
days. 
• Incidence of relapse or progression of primary malignancy. 
• Overall quality of life as measured by EuroQol 5 Dimensions (EQ-5D) questionnaires. 
• Global impression of change and severity. 

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3 
STUDY DESCRIPTION 
3.1 
Summary of Study Design 
This is a Phase 3, multicenter, double-blind, placebo-controlled study to assess the efficacy and 
safety of PSL compared to placebo for the treatment of participants with virus-associated HC 
following allogeneic HCT.  
The study hypothesis is that the administration of PSL to participants with virus-associated HC 
will demonstrate superiority for the time to resolution of HC (as measured by resolution of 
macroscopic hematuria) compared to participants treated with placebo. The primary hypothesis 
will be tested in participants with BKV viruria to demonstrate superiority over placebo in this 
population (BK Intent-to-Treat [ITT] Population). A supplementary analysis will be conducted in 
all participants with any virus-associated HC (BKV, AdV, CMV, HHV-6, JCV, and/or EBV) in 
order to evaluate efficacy in this broader population (ITT Population). Further detail is provided 
in Section 9.2.1.1 and will be described in the Statistical Analysis Plan (SAP). 
Participants who meet all of the inclusion criteria and none of the exclusion criteria will be 
randomized in a 
ratio to receive sequential infusions of PSL or placebo and will be monitored 
for resolution of macroscopic hematuria as defined by the primary endpoint. Randomization will 
be stratified by 
 
 
In the dosing strategy being evaluated in this study, all participants will receive  infusions of 
either PSL or placebo separated by
 (±3) days. Administering the 
 infusion as early as 
11 days after the first infusion is encouraged if feasible. Participants who weigh <40 kg at the time 
of screening will receive 
 
 (or placebo), while participants who weigh ≥40 kg at the 
time of screening will 
 
 (or placebo). Cryopreservation media (without 
cells) will serve as the placebo and will be identical in volume and appearance upon administration. 
All infusions will be administered IV (via peripheral or central line) over approximately minutes 
as a slow push. 
To support the primary objective, all randomized participants will undergo regular visual 
assessments of freshly collected urine samples by Bedi grading47 with urinalysis. 
In support of the key secondary objective, bladder pain will be assessed using age-appropriate 
COAs. 
Participants will also have urine and blood samples sent at prespecified intervals during the study 
to monitor viral loads of all the viruses targeted by PSL (BKV, AdV, CMV, HHV-6, JCV, and 
EBV). For participants who develop symptoms and/or signs of possible virus-associated 
gastrointestinal (GI) disease, and whose treating physician determines that laboratory evaluation 
of stool specimens for diagnostic and/or monitoring reasons is clinically indicated, stool samples 
for AdV and CMV viral load determination should, when possible, be sent to the central laboratory. 
Similarly, for participants who develop symptoms and/or signs of possible virus-associated 
neurological disease, and whose treating physician determines that laboratory evaluation of CSF 
for diagnostic and/or monitoring reasons is clinically indicated, CSF samples for CMV, HHV-6, 
and JCV viral load determination should, when possible, be sent to the central laboratory. In all 
cases, CSF samples required for routine clinical care of the participant take precedence over these 
study-related evaluations. 

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Safety assessments, including chemistries, complete blood counts with differentials, and physical 
examinations, will be performed. Adverse events will be assessed. 
As GVHD is a theoretical safety concern, the incidence and severity of GVHD will be monitored 
during the study. No participants will be permitted to receive a second infusion of PSL or placebo 
if they develop worsening of GVHD (ie, relative to baseline GVHD at the time of randomization) 
at the proposed time of infusion of the second dose.  
The following data will be recorded in the electronic case report form (eCRF): blood group/type, 
primary malignancy or underlying disease, prior therapy for malignancy, conditioning regimen for 
HCT, HCT donor blood type and CMV serostatus, type of HCT, and date of engraftment. 
Treatment with supportive therapies, other intravesicular agents for the control of bleeding 
(including, but not limited to, aminocaproic acid), antispasmodics, treatment for pain control 
(including opioids), and blood product transfusion support are permitted. Definitive therapies to 
stop bladder bleeding, such as cystectomy, bladder vessel embolization, cauterization, application 
of fibrin “glue” preparations, or formalin instillation are permitted but will be considered treatment 
failures for the primary endpoint of time to resolution of macroscopic hematuria. Analgesic use 
will be collected daily on a medication log for inpatients (to be collected by study staff) and a pain 
medication log within the electronic patient-reported outcome (ePRO) system for outpatients (to 
be reported by participants). Clinically available (ie, not investigational) antiviral agents prescribed 
for other infections, such as foscarnet and ganciclovir to treat CMV, are allowed (data on their use 
will be collected along with other concomitant medications). 
Participants will continue to be followed on the study for 24 weeks after the participant’s first 
infusion with study treatment. The overall enrollment period will be approximately 15 months. 
A summary of the study design is shown in Figure 1. 
 
Figure 1. 
Summary of Study Design 
 
3.2 
Data and Safety Monitoring Board 
An independent Data and Safety Monitoring Board (DSMB) will be convened for this study to 
routinely monitor participant safety and evaluate prespecified interim analyses to determine 
whether to stop the study early for futility or success. The DSMB will receive summary reports of 
all serious adverse events (SAEs) and adverse events of special interest (AESI; see Section 8.1.4) 
at least monthly. In addition, the DSMB will receive expedited reporting of all individual, 

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unexpected, related SAEs occurring within 14 days of an infusion of study drug, and 
infusion-related AESI of at least Grade 2 severity occurring within 24 hours of an infusion. A 
DSMB charter, detailing all aspects of the DSMB’s composition, scope of review, and procedures 
will be described in a separate document. In addition, the DSMB will review safety data at the 
following times: 1) after 9 to 15 participants have been randomized and then again at routine 
intervals; 2) after five children ≥1 and <6 years of age have been randomized; and 3) at additional 
ad hoc meeting(s) if determined necessary by the Sponsor or DSMB Chair. The DSMB will review 
the pre-specified interim analysis to determine whether to stop the study early for futility or success 
(described in Section 9.2.3). An unblinded statistician will be assigned to the DSMB. This 
statistician will not be involved in any aspects of study conduct outside of the DSMB, and their 
role will be defined in the DSMB charter. 
3.3 
Justification for the Study Design 
The use of placebo in this clinical study is justified for the following reasons:  
• Since the natural history of virus-associated HC in the HCT population is variable and not 
readily predictable, a placebo control group is required to provide an objective, 
contemporaneous assessment of the therapeutic effects and adverse event profile of PSL 
• The use of an active control group in the study is not feasible since there are no approved, 
efficacious antiviral therapies for the treatment of virus-associated HC. 
Male or female participants of any age will be included in this study, but enrollment of participants 
<1 year of age will occur only once preliminary safety data are available from 5 participants ≥1 
and <6 years of age. The DSMB will review 4-week data from 5 participants ≥1 and <6 years of 
age once available and make a recommendation as to whether to proceed with enrolling 
participants <1 year of age. 
The inclusion of pediatric participants in this study is justified for the following reasons:  
• Virus-associated HC is a well-described complication of HCT in both adult and pediatric 
patients;48,49,50  
• Children with HC after HCT are considered to fall into a high-risk category due to their 
associated high mortality and significant genitourinary morbidity;51  
• There are no approved, efficacious antiviral therapies for the treatment of virus-associated 
HC; and  
• In the Phase 2 CHARMS study, 17 of 58 participants enrolled (29%) were <18 years of 
age, with the youngest 2 years of age. This previous clinical pediatric experience with PSL 
supports the inclusion of participants <18 years of age in this study. 
 

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4 
SELECTION AND WITHDRAWAL OF SUBJECTS  
4.1 
Inclusion Criteria 
Participants must meet all of the following criteria in order to be eligible to participate in the study: 
1. Male or female of any age, but enrollment of participants <1 year of age at the time of informed 
consent will occur only once preliminary safety data are available from 5 participants ≥1 and 
<6 years of age. See Section 3.3 for details.  
2. Had an allogeneic HCT performed ≥21 days and ≤1 year prior to randomization. 
3. Myeloid engraftment confirmed, defined as an absolute neutrophil count ≥500/mm3 for 
3 consecutive laboratory values obtained on different days, and platelet count >10,000/mm3 at 
the time of randomization. Platelet transfusions are permitted.  
4. Diagnosed with HC based on meeting all of the following criteria: 
a. Clinical signs and/or symptoms of cystitis, such as dysuria, urinary frequency, urinary 
urgency, lower abdominal pain or tenderness, and/or bladder pain, tenderness, or 
spasms. 
b. Bedi Grade 3 hematuria, defined as macroscopic hematuria with visible clots. 
c. Viruria with ≥1 target virus (ie, BKV, AdV, CMV, HHV-6, JCV, and/or EBV). 
Randomization of participant may be based on viruria data obtained from either the 
local or central laboratory. 
5. At least 1 identified, suitably matched PSL cell line for infusion is available.  
6. Willing and able to provide written informed consent to participate in the study, or a parent or 
legal guardian is willing and able to provide written informed consent and the potential 
pediatric participant is able to provide assent in a manner approved by the Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) and local regulations. 
7. Women of childbearing potential (WOCBP) and men whose sexual partners are WOCBP must 
agree to use contraception during the study and for a minimum of 90 days after study treatment 
as detailed in Appendix H; participants must also refrain from donating sperm or eggs during 
the study and for at least 90 days after treatment completion.  
8. Has a negative serum pregnancy test for female participants of childbearing potential. 
4.2 
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from participation in the study: 
1. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose >0.5 mg/kg/day 
or equivalent). 
2. Therapy 
with 
antithymocyte 
globulin, 
alemtuzumab 
(Campath-1H), 
or 
other 
immunosuppressive T cell-targeted monoclonal antibodies ≤28 days before randomization. 
3. Evidence of active Grade >2 acute GVHD (see Appendix E for acute GVHD grading). 

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4. Uncontrolled or progressive bacterial or fungal infections (ie, evidence of bacteremia, 
fungemia, dissemination, and/or organ-specific infection not well controlled by present 
therapies). 
5. Uncontrolled or progressive viral infections (ie, evidence of viremia, dissemination, and/or 
organ-specific infection not well controlled by present therapies) not targeted by PSL. 
6. Uncontrolled or progressive EBV-associated post-transplant lymphoproliferative disorder. 
7. Known or presumed pneumonia secondary to any organism that is not considered to be 
well-controlled by antimicrobial therapy (ie, clinically stable for ≥7 days on a stable 
antimicrobial regimen). 
8. Donor lymphocyte infusion performed ≤21 days before randomization. 
9. Hemodynamic or respiratory instability defined as either of the following: 
a. Requirement for continuous infusions of inotropes or vasopressors for blood pressure 
support. 
b. Requirement for endotracheal intubation or mechanical ventilation. 
10. Hemoglobin <7 g/dL despite RBC transfusions. 
11. Clinically significant coagulopathy that, based upon the assessment of the Investigator, could 
result in an increased risk of active bleeding not attributed to hemorrhagic cystitis. 
12. Ongoing use of systemic anticoagulant drugs or antiplatelet drugs. 
13. Evidence of active hepatic sinusoidal obstruction syndrome. 
14. Liver dysfunction, defined as liver transaminases (ie, aspartate aminotransferase or alanine 
aminotransferase) >5 × upper limit of normal (ULN) or direct bilirubin >3 × ULN unless the 
participant has a chronic and stable diagnosis that accounts for the abnormality(ies) and 
eligibility is approved by the AlloVir Medical Monitor. 
15. Requiring renal replacement therapy ≤7 days prior to randomization.  
16. Evidence of encephalopathy. 
17. Relapse of primary malignancy. 
18. Receipt of other investigational antiviral treatments (eg, brincidofovir) ≤7 days prior to 
randomization. 
19. Pregnant, lactating, or planning to become pregnant. 
20. History of severe (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≥3) 
allergy to any component of PSL (including human serum albumin and dimethyl sulfoxide) or 
history of severe (CTCAE Grade ≥3) prior reactions to blood product transfusions. 

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21. Any condition that, in the opinion of the Investigator, would compromise the safety of the 
participant, prevent study participation, or interfere with the evaluation of study endpoints. 
4.3 
Withdrawal Criteria 
4.3.1 
Withdrawal From the Study 
Participation in this clinical study will be discontinued for any of the following reasons: 
• The participant (or parent or legal guardian) withdraws consent. 
• The participant (or parent or legal guardian) requests discontinuation from the study for any 
reason. 
• Occurrence of any medical condition or circumstance that exposes the participant to substantial 
risk by remaining in the study. 
• Any SAE, clinically significant adverse event, severe laboratory abnormality, intercurrent 
illness, or other medical condition that indicates to the Investigator that continued participation 
is not in the best interest of the participant.  
• Participant failure to comply with protocol requirements or study-related procedures making 
them unsuitable for continuation in the opinion of the Investigator. 
• Termination of the study by the Sponsor or the regulatory authority. 
If a participant withdraws prematurely from the study due to any of the above criteria or any other 
reason, study staff should make every effort to complete an Early Termination Visit. The 
assessments for the Early Termination Visit are the same as those described for the Week 24 
(Day 168) Visit. The reason for participant withdrawal must be documented in the eCRF. 
In the case of participants lost to follow-up, attempts to contact the participant must be made and 
documented in the participant’s medical records. 
Withdrawn participants will not be replaced. 
4.3.2 
Discontinuation of Study Treatment 
The following do not fulfill any of the criteria for withdrawal from the study but do make the 
participant ineligible to receive any additional infusions of study treatment: 
• Development of irreversible, life-threatening, Grade 3 to 4 acute GVHD or a Grade 3 to 4 
non-hematologic adverse event between the first and second doses of PSL or placebo that is 

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considered related to study treatment administration. If this occurs, the participant’s toxicities 
will be followed until resolution or until the participant’s participation in the study ends. 
• Receipt of any other hematopoietic stem cell product.  
• Receipt of therapy for relapse of the participant’s primary malignancy.  
• Occurrence of Grade 3 or 4 CRS that persists beyond 72 hours. If this occurs, the participant’s 
toxicities will be followed until resolution or until the participant’s participation in the study 
ends. 
•  Pregnancy. 
If any of the above criteria are met, every effort should be made to keep the participant in the study 
and continue follow-up. 
4.4 
Pre-Screening 
Participants may complete an optional Pre-Screening Visit to evaluate urine viral loads (for BKV, 
AdV, CMV, HHV-6, JCV, and EBV) to allow sites to send samples to the central laboratory to 
expedite eligibility confirmation. The optional Pre-Screening Visit may be conducted up to 
14 days prior to randomization (at the Baseline Visit). A separate Pre-Screening consent form is 
available for this purpose.  
4.5 
Screen Failures 
Screen failures are defined as participants who have signed the Informed Consent Form (ICF) to 
participate in the clinical study but are not randomized into the clinical study. Participants who 
have signed only the Pre-Screening Consent Form will not be considered screened for the purpose 
of defining screen failures. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, 
documentation of HLA typing, and any SAEs. 
Individuals who do not initially meet criteria for participation in this clinical study (screen failure) 
may be rescreened once after discussion with the Medical Monitor. 

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5 
STUDY AND SITE CLOSURE 
The Sponsor reserves the right to close a study site or terminate the study at any time for any reason 
at the sole discretion of the Sponsor. Study sites will be closed upon study completion. A study 
site is considered closed when all required documents and study supplies have been collected and 
a study site closure visit has been performed. 
The Investigator may initiate study site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include, but are 
not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor's procedures, or Good Clinical Practice (GCP) guidelines 
• 
Inadequate recruitment of participants by the Investigator 
• 
Discontinuation of further study intervention development 

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6 
STUDY TREATMENTS 
6.1 
Treatment Groups 
This is a Phase 3, multicenter, double-blind, placebo-controlled study to assess the efficacy and 
safety of PSL compared to placebo for the treatment of participants with virus-associated HC 
following allogeneic HCT. Participants who meet all the inclusion criteria and none of the 
exclusion criteria will be randomized in a 
 ratio to receive
 sequential infusions of PSL or 
placebo. 
. Administering the 
 as early as feasible within this window is encouraged. Based on body weight at 
the time of screening, participants who weigh <40 kg will receive 
 
or placebo), 
while participants who weigh ≥40 kg will receive 
 
 (or placebo).  
6.2 
Rationale for Dosing 
Study treatment is to be administered at a fixed dose based on weight, as  sequential infusions of 
PSL cells or placebo. The fixed, weight-based doses were selected based on data from previous 
clinical studies in which PSL was well tolerated, safe, and effective. 
The dose of PSL per infusion (
 
 
 
 is designed to mimic the VST dose administered in the CHARMS study. In the CHARMS 
study, the protocol-specified VST cell dose was 2×107/m2 per infusion. A retrospective analysis 
of actual doses administered in the CHARMS study demonstrated that, on average, participants 
who weighed <40 kg received 
 cells per infusion (n = 9) while those who weighed 
≥40 kg received 
 cells per infusion (n = 45).  
In order to increase the repertoire of T cells potentially to be provided to each participant, the cell 
lines chosen for the first and second infusions of PSL may come from different donors (see 
Section 6.5.1 for details). 
For additional information related to previous clinical studies with PSL, see the current IB. 
6.3 
Randomization and Blinding 
Participants who meet all of the inclusion criteria and none of the exclusion criteria will be 
randomized to the study per the Schedule of Procedures. Participants will be randomized in a 
 
ratio to receive  sequential infusions of PSL or placebo, with the first dose administered on Day 0. 
Randomization assignments will be performed by the Interactive Response Technology (IRT) 
system. Randomization will be stratified by 
 
 
6.4 
Breaking the Blind 
The Sponsor designee (ie, IRT vendor) will have a designated randomization administrator who 
will maintain the randomization codes in accordance with standard operating procedures to ensure 
the blind integrity is properly maintained. Care should be exercised to ensure that only Sponsor 
personnel who require knowledge of treatment assignments will be unblinded (eg, staff involved 
in Suspected Unexpected Serious Adverse Reaction [SUSAR] reporting). 

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An unblinded statistician will be assigned to the DSMB. This statistician will not be involved in 
any aspects of study conduct outside of the DSMB, and their role will be defined in the DSMB 
charter. 
Unblinding should only occur in the event of an emergency or adverse event for which it is 
necessary to know the study treatment to determine an appropriate course of therapy. If the 
participant’s study treatment must be unblinded, the Investigator or qualified designee should 
contact IRT for the study treatment information. The IRT documentation indicating the blind break 
at the site must be retained with the participant’s source documentation in such a way as to avoid 
unblinding the treatment assignment to other site or Sponsor-blinded personnel. 
If possible, the Investigator should attempt to contact the Medical Monitor prior to unblinding in 
order to get additional information about the study treatment. If not possible, the Investigator 
should notify the Medical Monitor as soon as possible of the unblinding without disclosing the 
treatment assignment of the unblinded participant. The Investigator must document the 
participant’s identification, the reason for breaking the blind, and the date and time for breaking 
the blind.  
6.5 
Drug Supplies 
6.5.1 
Selection of Study Drug for the First and Second Dose and Formulation Packaging 
Posoleucel is a third-party, donor-derived, “off-the-shelf,” VST product with specificity for BKV, 
AdV, CMV, HHV-6, and EBV (with additional cross-reactive specificity for JCV) that is 
cryopreserved and ready for immediate use. For more information, see the current IB. 
Posoleucel will be checked for cell concentration, viability, identity, phenotype, potency, 
endotoxin, mycoplasma, and sterility. The final product will be cryopreserved for future use as an 
“off-the-shelf” VST product.  
Posoleucel cell lines will be selected for each participant based on 
 
. The HLA alleles used for evaluation 
of matching are HLA-A, HLA-B, HLA-DR, and, if available, HLA-DQ. 
The appropriate PSL cell line(s) will be selected using a software program (CytoMatch™), 
 
 
 
 
 
 
 
 
 
 
 
  
The selection of PSL cell line for the first infusion will be that with the highest match identified 
by the CytoMatch system. The PSL cell line or placebo lot for the second infusion will be selected 
based on the following: 

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• For participants who have demonstrated an initial clinical response, defined by a reduction 
of ≥1 grade on the Bedi scale 11 (+3) days after the first infusion, the same PSL cell line 
(or placebo lot) as initially administered will be infused for the participant’s 
 
 If there is more than one Bedi score within the window, the assessment closest to 
the scheduled second infusion should be used. 
• For participants who have not demonstrated an initial clinical response, the next-best match 
according to the CytoMatch hierarchy will be used as long as there are 
 
 If a 
suitable cell line for the 
 cannot be identified from available inventory, a 
 of the initial cell line administered or placebo from the same lot as the first 
dose will be administered.  
As GVHD is a theoretical safety concern, the incidence and severity of GVHD will be monitored 
during the study. No participants will be permitted to receive a second infusion of PSL or placebo 
if they develop worsening of GVHD (ie, relative to baseline GVHD at the time of randomization) 
at the proposed time of infusion of the second dose.  
Posoleucel will be supplied as a dispersion for infusion, in 6 mL-capacity closed vials at a 
concentration of 
 
.  
Posoleucel will be frozen in cryopreservation media containing 
 
 
Cryopreservation media (without cells) will serve as the placebo and will be identical in volume 
and appearance when administered. 
6.5.2 
Study Drug Preparation, Dispensing, and Administration 
Posoleucel and placebo will be supplied in cryovials, which are to be transported from liquid 
nitrogen storage at the clinical site to the cell-thawing and preparation location in a liquid nitrogen 
Dewar or other suitable container. Details of the cell thawing, preparation for dosing, and 
administration to the participant will be provided to clinical sites in a separate Cell Therapy 
Manual. 
Cryovials of PSL and placebo will be removed from liquid nitrogen storage and thawed, and the 
contents transferred to a syringe prior to infusion as described in detail in the Cell Therapy Manual. 
Study treatment is to be infused into the participant within 30 minutes of thawing (from completion 
of thaw to completion of infusion). If the location of the participant is remote from the clinical 
site’s cell storage facility, the thawing of the cryovials and preparation of infusion syringes should 
be conducted in an appropriate location for cell preparation that is sufficiently close to the 
participant to ensure that no more than 30 minutes elapse between the completion of thawing and 
infusion. 
Premedication is not required, except for participants with a prior history of reaction to blood 
products who may receive premedication with diphenhydramine 0.25 to 0.5 mg/kg IV or orally 
(maximum dose of 25 mg) or a similar antihistamine preferred by the study site and/or 
acetaminophen (paracetamol) 5 to 10 mg/kg IV or orally (maximum dose of 1000 mg) prior to 
study treatment administration. Premedication with high-dose systemic corticosteroids 
(ie, prednisone dose >0.5 mg/kg/day or equivalent) is prohibited. 

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All infusions of PSL or placebo will be administered IV (via central or peripheral line) over 
approximately minutes as a slow push. 
Participants will be monitored according to institutional standards for the administration of blood 
products and, at a minimum, according to the following requirements: 
• Participants in an outpatient setting must remain in the clinic for ≥1 hour after the end of the 
infusion. 
• Vital signs and pulse oximetry will be monitored at baseline and also after the final flush has 
been administered according to Appendix A.  
All findings must be recorded in the eCRF. 
If a participant experiences an infusion reaction, then diphenhydramine 0.25 to 0.5 mg/kg IV or 
orally (maximum dose of 25 mg) or a similar antihistamine preferred by the study site may be 
administered as treatment (even if received as premedication). Acetaminophen (paracetamol) 5 to 
10 mg/kg IV or orally (maximum dose of 1000 mg) may also be given if it was not given as 
premedication or if 6 hours has elapsed since the prior dose. In the case of suboptimal control of 
an infusion reaction or the need to use corticosteroids for treatment of an infusion reaction, doses 
of ≤0.5 mg/kg/day of prednisone or equivalent should be considered first.  
Participants will receive supportive care for acute or chronic toxicity, including blood components, 
antibiotics, or other interventions as appropriate per local treatment guidelines. See Section 6.6.2 
for additional information. 
Further details concerning study treatment receipt, storage, and administration will be provided to 
clinical sites in a separate Cell Therapy Manual. 
6.5.3 
Treatment Compliance 
Posoleucel or placebo will be administered only IV and only under the direct supervision of clinical 
study personnel at the site. 
6.5.4 
Storage and Accountability 
Posoleucel or placebo is stored in the vapor phase of liquid nitrogen in a continuously monitored 
storage freezer. 
All material containing PSL or placebo will be treated and disposed of as hazardous waste in 
accordance with governing regulations and clinical site procedures. 
Posoleucel and placebo accountability are the responsibility of the Principal Investigator and 
Sponsor. However, this responsibility may be delegated to a suitably qualified Investigator who 
has had appropriate study-specific training that has been documented. The Sponsor will maintain 
records that will allow anonymous traceability of each PSL cell line to the third-party PBMC donor 
from whom it originated. These records will be maintained for 30 years after expiry for each PSL 
cell line. 
Detailed records will be maintained to allow for accurate accountability of PSL and placebo as per 
applicable Sponsor and clinical site procedures. For further details and specifications, see the Cell 
Therapy Manual. 

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6.6 
Prior and Concomitant Medications 
6.6.1 
Prohibited Medications 
All participants may receive therapy for HC with cidofovir (IV or through intravesical instillation), 
fluoroquinolones (eg, ciprofloxacin), or leflunomide, provided that these agents are initiated prior 
to randomization. Initiation of these agents for the treatment of HC during the first 6 weeks is 
prohibited. These agents should not be discontinued during the first 6 weeks after randomization 
unless needed to manage toxicity. Dose changes should not be made during the first 6 weeks unless 
needed for renal dose adjustment.  
Use of cidofovir during the first 6 weeks of the study for the treatment of non-HC-associated AdV 
or another non-HC viral infection is permitted, but should be discussed with the Medical Monitor. 
Receipt of other investigational antiviral treatments (eg, brincidofovir) ≤7 days prior to 
randomization and throughout the duration of the study is prohibited.  
T cell ablative therapies, such as antithymocyte globulin, alemtuzumab (Campath-1H), or other 
immunosuppressive T cell-targeted monoclonal antibodies, are prohibited during the study. Use 
of corticosteroids ≥0.5 mg/kg/day prednisone (or equivalent) should not be administered during 
the study unless clinically required. 
COVID-19 vaccination should be avoided for at least 28 days following the second infusion of 
study treatment (PSL or placebo) when feasible to minimize confounding due to the possible 
overlap of adverse effects (see Section 1.5.3).  
6.6.2 
Supportive Care 
Supportive care measures such as the following are permitted: 
• Use of intravesicular agents for the control of bleeding 
• Analgesics, including opioids/ates (data will be collected daily) 
• IV hydration 
• Continuous bladder irrigation 
• Antispasmodics 
• Transfusion of RBCs 
• Transfusion of platelets 
• Transfusion of fresh frozen plasma 
• Nephrostomy tube placement 
All supportive care measures must be documented in the participant study records and the eCRF. 
6.6.3 
Documentation of Prior and Concomitant Medication Use 
Medications used within 30 days before screening will be recorded. However, the following 
medications used within 30 days before screening do not need to be recorded: 
• Fluids 

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• Electrolytes 
• Vitamins 
• Supplements  
• Mouth care 
• Laxatives 
• “As needed” medications other than pain medications, which need to be collected 
At screening, all concomitant medications and concurrent therapies, including the ones listed 
above, will be documented as indicated in Appendix A. Dose, route, unit frequency of 
administration, indication for administration, and dates of medication will also be captured in 
source documents and on the appropriate eCRF.  

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7 
EFFICACY ASSESSMENTS 
The primary endpoint is the time to resolution of macroscopic hematuria in participants with 
documented BK viruria. Resolution of macroscopic hematuria is defined as resolution to Grade 0 
or 1 on the Bedi scale47 as assessed by an HCP on the study team on 2 consecutive visual urine 
assessments ≥2 days apart without continuous bladder irrigation or nephrostomy tubes; Grade 1 
hematuria requires confirmation of resolution by urinalysis results of ≤100 RBCs/high power field 
(HPF). If a participant has nephrostomy tubes that are capped, Bedi assessments may be 
performed, including for the purpose of assessing for resolution. Details of the macroscopic 
hematuria assessment are provided in Section 7.1. 
The key secondary endpoint is the time to resolution of bladder pain as measured by 
age-appropriate COAs. Resolution of bladder pain is defined as participants achieving a score on 
the relevant COA that does not exceed “mild pain” without use of prescription pain medications 
or the use of supportive bladder care. 
Mild bladder pain is defined as:  
• In participants ≥12 years of age: a score ≤3 on the worst daily pain question from the 
Bladder Pain/Interstitial Cystitis Symptom Diary (BPIC SD). 
• In participants 3 to 11 years of age: a score ≤2 on the Wong-Baker FACES® Pain Rating 
Scale.  
This endpoint will not be assessed in participants <3 years of age as there is no COA that has been 
validated for this purpose. Instead, data regarding pain behaviors will be collected in this age group 
using the Patient-Reported Outcomes Measurement Information System® (PROMIS) Parent Proxy 
Pain Behavior Short Form.  
Additional secondary efficacy endpoints include the following:  
• Number of days in the hospital (for any reason including, but not limited to, HC) over the 
24-week study period. 
• Time to resolution of viremia for all target viruses (ie, BKV, AdV, CMV, HHV-6, JCV, and/or 
EBV) over the 24-week study period (only for participants with detectable viremia at baseline). 
Evaluation of this endpoint will be based on viremia quantitation performed at the central 
laboratory. Resolution of viremia will be defined by the lower limits of detection of the assays 
used. 
• Average daily bladder pain (including lower abdominal pain, bladder-related pressure, and/or 
spasm pain or dysuria) over the initial 6 weeks following randomization. 
The exploratory efficacy endpoints include the following: 
• Cumulative days and time to discontinuation of supportive therapy for HC, including IV 
hydration, continuous bladder irrigation, and/or nephrostomy tube placement. 
• Incidence and time to resolution of HC-associated signs and symptoms other than bladder pain. 
• Incidence and time to recurrence of HC-associated signs and symptoms, including bladder 
pain, bladder pressure, spasms, urinary frequency, urinary urgency, nocturia, dysuria, and/or 
the presence of blood clots in urine. 

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• Requiring RBC and/or platelet transfusions and the number of required RBC and/or platelet 
transfusions (measured in transfusion units/participant). 
• Change in renal function as assessed by eGFR. For participants requiring dialysis, number of 
days on dialysis will be captured. 
• Time to resolution of BK viruria. Resolution of viruria will be defined by the lower limits of 
detection of the assay used. 
• Resolution of macroscopic hematuria as assessed at Weeks 2, 4, 6, 8, and 12 after 
randomization. 
• Level of pain as assessed at Weeks 2, 4, 6, 8, and 12 after randomization. 
• Time to resolution of non-BK target viral infections (ie, associated signs, symptoms, and 
presence/absence of viral load in blood and/or urine for AdV, CMV, HHV-6, JCV, and/or 
EBV) present at the time of randomization. Peripheral blood and, where relevant, urine 
(ie, evidence of virus in the urine at baseline), will be monitored for AdV, CMV, HHV-6, JCV, 
and/or EBV viral load. 
• Incidence of target viral reinfections (ie, BKV, AdV, CMV, HHV-6, JCV, and/or EBV) as 
defined by new onset viremia or viruria and the presence of associated symptoms relative to 
baseline. 
• Length of use of IV narcotic medication(s) for control of lower abdominal/bladder pain. 
• Length of use of any pain medication(s) (IV, oral, or both), including antispasmodics used for 
pain, for control of lower abdominal/bladder pain. 
• Length of use of immunosuppressive agents, by specific agent used (including dose and 
changes in dose). 
• Number of hospitalizations/re-hospitalizations for any reason. 
• Cumulative incidence and severity of chronic GVHD. 
• Incidence and duration of use of any other antiviral therapies (eg, ganciclovir, valganciclovir, 
foscarnet) during the study. 
• Overall survival, defined as time to death (from any cause) from the time of randomization in 
days. 
• Incidence of relapse or progression of the primary malignancy. 
• Overall quality of life as measured by EQ-5D questionnaires. 
• Global impression of change and severity. 
7.1 
Macroscopic Hematuria Assessment  
7.1.1 
Overview 
The primary endpoint is the time to resolution of macroscopic hematuria in participants with 
documented BK viruria. A supplementary analysis will evaluate the time to resolution of 
macroscopic hematuria in participants with any virus-associated HC. Resolution of macroscopic 

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hematuria is defined as resolution to Grade 0 or 1 on the Bedi scale47 as assessed by an HCP on 
the study team on 2 consecutive visual urine assessments ≥2 days apart without continuous bladder 
irrigation or nephrostomy tubes. However, if a participant has nephrostomy tubes that are capped, 
Bedi assessments may be performed, including for the purpose of assessing for resolution. An 
HCP on the study team (including a home health provider) may perform the visual urine 
assessment, but it is the Investigator’s responsibility to determine the Bedi score. The same urine 
sample should be used for the HCP’s urine visual assessment and the urinalysis. All visual urine 
assessments with urinalyses should be performed on freshly collected urine specimens; urine 
should ideally be collected in the morning, but do not collect the first void of the day. For details 
regarding urine collection procedures, refer to the urine collection instructions appropriate for the 
participant’s age and site of care. 
Although two urine assessments (each including a Bedi assessment with urinalysis) are required 
to establish resolution of macroscopic hematuria, time to resolution will be calculated from the 
date of randomization to the date of the first visual urine assessment without macroscopic 
hematuria (by the Hemostick® visual scale for outpatients; by the Bedi scale for inpatients).  
The schedule for visual assessments of the urine and urinalysis is discussed below and summarized 
in Appendix A. 
7.1.2 
Hematuria Grading Using the Bedi Criteria 
The determination of the Bedi grade is primarily a clinical assessment (ie, visual urine assessment), 
but additional data are also required as outlined in the Bedi criteria and in Figure 2 below. 
Urinalysis includes an evaluation for blood and should reflex to microscopy if positive. 
Hematuria grade is adapted from the Bedi criteria47:  
• Grade 0: No hematuria; urine appears clear or yellow (ie, non-bloody) on visual assessment; 
urinalysis is negative for blood. Urine microscopy is not required if urinalysis is negative for 
blood. 
• Grade 1: Microscopic hematuria; urine appears clear on visual assessment, but urinalysis is 
positive for blood and urine microscopy shows ≤100 RBCs/HPF.  
• Grade 2:  
o Macroscopic hematuria but no clots on visual assessment; the absence of clots must be 
confirmed by an HCP.  
OR 
o Microscopic hematuria; urine appears clear on visual assessment, but urinalysis is 
positive for blood and urine microscopy shows >100 RBCs/HPF. 
• Grade 3: Macroscopic hematuria with evidence of visible clots; clots are defined as gelatinous 
or semi-solid masses of blood in urine, and presence must be confirmed by an HCP.  
• Grade 4: Same as Grade 3 with HC-associated renal impairment (new onset elevation of 
creatinine to ≥1.5 × ULN and considered by the Investigator to be HC-related) or transfusion 
requirements secondary to hematuria (packed RBCs and/or platelets). On the rare occasion 
where participants have macroscopic hematuria but no clots (eg, in the setting of low platelets) 
and have an HC-related transfusion requirement, the Bedi grade should be assessed as Grade 4. 

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A schema for determining the Bedi grade is displayed in Figure 2. 
Figure 2. Schema for Determining the Bedi Grade from Urine Visual Assessment, 
Laboratory Data, and Clinical Evaluation 
 
7.1.3 
Hemostick® Visual Scale for Outpatients 
The Hemostick is a printed visual scale with 6 color fields that standardizes the characterization 
of macroscopic hematuria severity.52 The numbering of the Hemostick scale does not map directly 
to the Bedi grade. The Hemostick will be used as a monitoring tool for outpatients. A Hemostick 
score of 0 or 1 will trigger two hematuria visual assessments with Bedi grading by an HCP on the 
study team, each with an accompanying urinalysis; these assessments will be used to confirm 
resolution of macroscopic hematuria. Similarly, following resolution of macroscopic hematuria, 
Hemostick assessments will be used for outpatients to monitor for potential relapse. Participants, 
caregivers, and home health providers (if needed) will be trained to use and interpret the Hemostick 
in the outpatient setting via an instruction manual. For an image of the Hemostick visual scale, 
please visit https://hemostick.com/engelska/picture. 
7.1.4 
Timing of Urine Visual Assessments with Urinalyses 
All randomized participants will undergo regular visual assessments of freshly collected urine 
samples for: 1) the presence or absence of visible blood, and 2) the presence or absence of blood 

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clots. The schedule of assessments for each participant will be determined by the treatment location 
(inpatient vs outpatient), time on study (through the end of Week 6 [Day 42] vs after Week 6), and 
status of macroscopic hematuria (unresolved vs resolved), as shown in Table 2. Each time that a 
participant undergoes a urine visual assessment for Bedi grading, the same sample should be sent 
for urinalysis. 
Table 2. Timing of Visual Urine Assessments with Urinalysis 
Treatment 
Location 
Macroscopic 
Hematuria [1] 
Time on Study 
Through the End of 
Week 6 (Day 42) 
After Week 6 (Day 43) 
Inpatient 
Unresolved 
Bedi assessment with U/A 
3 × per week 
Bedi assessment with U/A 
2 × per week ≥2 days apart 
Resolved 
Bedi assessment with U/A 
1 × per week 
Bedi assessment with U/A 
1 × per week 
Outpatient 
Unresolved 
Hemostick daily; 
Bedi assessment with U/A 
1 × per week  
Hemostick 2 × per week 
≥2 days apart;  
Bedi assessment with U/A 
1× per week  
Resolved 
Hemostick 1× per week; 
Bedi assessment with U/A 
1 × per week 
Hemostick 1 × per week; 
Bedi assessment with U/A 
at Week 12 and 24 study 
visits 
[1] Resolved macroscopic hematuria is defined as resolution to Grade 0 or 1 on the Bedi scale as assessed by an HCP 
on the study team on 2 consecutive visual urine assessments ≥2 days apart without continuous bladder irrigation or 
nephrostomy tubes. However, if a participant has nephrostomy tubes that are capped, Bedi assessments may be 
performed, including for the purpose of assessing for resolution. 
Abbreviations: HCP = healthcare provider; U/A = urinalysis 
 
If participants develop a recurrence of hematuria, refer to Section 7.1.9 for guidance. 
7.1.5 
Urine Visual Assessment to Confirm Resolution of Macroscopic Hematuria 
Resolution of macroscopic hematuria is defined as resolution to Grade 0 or 1 on the Bedi scale47 
on 2 consecutive visual urine assessments ≥2 days apart without continuous bladder irrigation or 
nephrostomy tubes; Grade 1 hematuria requires confirmation of resolution by urinalysis results of 
≤100 RBCs/HPF. If a participant has nephrostomy tubes that are capped, Bedi assessments may 
be performed, including for the purpose of assessing for resolution. 
For inpatients, if absence of macroscopic hematuria is confirmed using the Bedi scale with 
urinalysis, the resolution date will be considered the date of the first of these 2 consecutive visual 
urine assessments. 
For outpatients, the earliest date of visual assessment without macroscopic hematuria (Hemostick 
value of 0 or 1) will trigger 2 laboratory urinalysis assessments ≥2 days apart to confirm the 
resolution of macroscopic hematuria. If absence of macroscopic hematuria is confirmed on 

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urinalysis (≤100 RBCs/HPF), the resolution date will be considered the first date of visual 
assessment without macroscopic hematuria using the Hemostick. 
7.1.6 
Urinalysis for Quantitation of Red Blood Cells 
Each time that a participant undergoes a Bedi assessment, a urinalysis should also be sent. During 
assessments for possible resolution of hematuria, urinalysis will be required to distinguish between 
Bedi Grade 1 and Bedi Grade 2.  
For RBC quantitation on urinalysis, some local clinical laboratories have an upper limit of RBC 
quantitation below 100 RBCs/HPF (eg, >25 RBCs/HPF, >50 RBCs/HPF). In these cases, if the 
urine is not grossly bloody on visual assessment, urine samples will be sent to the central laboratory 
for urine microscopy.  
7.1.7 
Pharmacologic Agents or Foods that May Cause Urine Discoloration 
If at any time during the study there is concern that a participant’s urine may be (or may become) 
discolored by a pharmacological agent (eg, phenazopyridine/pyridium) or by a dietary component 
(eg, beets), urinalysis should be performed to differentiate between macroscopic hematuria and 
urine discoloration.  
7.1.8 
Handling of Participants Receiving Definitive Therapies to Stop Bladder Bleeding, 
Continuous Bladder Irrigation, or Nephrostomy Tubes 
Definitive therapies to stop bladder bleeding, such as cystectomy, bladder vessel embolization, 
cauterization, application of fibrin “glue” preparations, or formalin instillation are permitted but 
will be considered treatment failures for the primary endpoint of time to resolution of macroscopic 
hematuria. Participants receiving continuous bladder irrigation or nephrostomy tubes should be 
evaluated daily by the Investigator for the ability to discontinue these supportive measures.  
For participants receiving continuous bladder irrigation or who have nephrostomy tubes, the 
primary endpoint (ie, time to resolution of macroscopic hematuria) will be measured once 
participants discontinue these modalities. Bedi grading will not be performed on days on which 
the participant is receiving continuous bladder irrigation or has nephrostomy tubes. However, if a 
participant has nephrostomy tubes that are capped, Bedi assessments may be performed, including 
for the purpose of assessing for resolution. Discontinuation of bladder irrigation and nephrostomy 
tubes will be based upon the participant’s clinical condition and the treating physician’s medical 
judgement. 
All attempts should be made to minimize urinary tract procedures or manipulations prior to urine 
collection to ensure that specimens are not contaminated due to trauma. 
7.1.9 
Assessments in Participants with Recurrence of Hematuria 
If, following resolution of macroscopic hematuria, recurrence is observed, a Bedi assessment with 
urinalysis will be obtained and the date of recurrence observed by the Investigator will be recorded. 
Urine obtained at the time of recurrence will also be sent for BKV, AdV, CMV, HHV-6, JCV, and 
EBV viral load determination and banking of viral DNA for potential genotyping. A second Bedi 
assessment with urinalysis will be repeated 48 to 72 hours after the date of recurrence observed by 
the Investigator. Recurrence is defined as 2 consecutive Bedi grades ≥2 (macroscopic hematuria). 
Participants with recurrence will then undergo visual assessment of urine and urinalysis as 

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indicated in Table 2 for those with unresolved hematuria and according to the participant’s 
treatment location and time on study.  Following resolution of recurrent hematuria, follow Table 2 
for those with resolved hematuria. 
7.2 
Clinical Outcome Assessments 
Age-appropriate COAs will be administered as indicated in Appendix B. Following consent, study 
site staff will review the age-appropriate COAs with the participant (or parent or other caregiver, 
as appropriate), using best practices demonstrated during the Site Initiation Visit and/or the 
Investigator Meeting.  
Participants (or parents or other caregivers) will be asked to enter information about the severity 
of pain on a hand-held device daily. If the COAs are not accessible on a hand-held device, paper 
versions of the questionnaires may be used. For participants for whom a COA is not available in 
an approved, validated translation, that COA will not be administered. The participant’s age at the 
time of informed consent/assent will determine which of the age-appropriate versions of the 
relevant COAs are administered. 
Use of the following COAs is anticipated for the measurement of bladder pain and analgesic use: 
• BPIC SD worst pain item (participants ≥12 years of age) – see Section 7.2.1 
• BPIC SD average pain item (participants ≥12 years of age) – see Section 7.2.1 
• Wong-Baker FACES Pain Rating Scale (participants 3 to 11 years of age) – see Section 7.2.2 
• PROMIS Parent Proxy Pain Behavior Short Form (8a) (participants <3 years of age) – see 
Section 7.2.3 
• Use of pain medications (participants of all ages) – see Section 7.2.4 
The following COAs will be administered to measure additional signs and symptoms of HC and 
urinary frequency: 
• BPIC SD items 8 and 9 (participants ≥12 years of age) – see Section 7.2.1 
o Urinary urgency (In the past 24 hours, how often did you have to rush to get to the bathroom 
to urinate?) 
o Constant need to urinate (In the past 24 hours, did you have a constant need to urinate?) 
• Interstitial Cystitis Symptoms Index (ICSI) items 2 and 3 (participants ≥12 years of age) – see 
Section 7.2.5 
o Urinary frequency (During the past 7 days, have you had to urinate less than 2 hours after 
you finished urinating?) 
o Nocturia (During the past 7 days, how often did you most typically get up at night to 
urinate?) 
The following COAs will be administered to measure overall quality of life (see Section 7.2.7): 
• EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire (participants ≥12 years of age) 
• EuroQol 5 Dimensions for Younger Patients (EQ-5D-Y) questionnaire (participants 8 to 
11 years of age) 

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• EQ-5D-Y Proxy Version 1 questionnaire (participants ≤7 years of age) 
The following age-appropriate Global Impression Scales will also be administered (see 
Section 7.2.6): 
• Patient Global Impression of Severity (PGIS) 
• Patient Global Impression of Change (PGIC) 
• Caregiver Global Impression of Severity (CGIS) 
• Caregiver Global Impression of Change (CGIC) 
7.2.1 
Selected Items from the Bladder Pain/Interstitial Cystitis Symptom Diary 
The BPIC Symptom Diary53 is a self-reported instrument designed to assess symptoms of bladder 
pain/interstitial cystitis on a daily basis. The adapted version that will be used in this study is 
comprised of 2 bladder pain NRSs (average and worst pain), and other urinary symptoms (2 items). 
The two items assess urinary urgency (In the past 24 hours, how often did you have to rush to get 
to the bathroom to urinate?) and the constant need to urinate (In the past 24 hours, did you have a 
constant need to urinate?). 
This assessment will be administered to participants ≥12 years of age at baseline, then daily 
through Week 6, followed by weekly to Week 24.  
7.2.2 
Wong-Baker FACES Pain Rating Scale 
The Wong-Baker FACES Pain Rating Scale54 is a self-reported measure designed to assess acute 
pain in young children. Children are instructed to select from 6 line-drawn faces to demonstrate 
“how they feel inside” from “no hurt” to “hurts worst.” Pictorial scales facilitate completion by 
children as they do not use sophisticated wording or abstract numerical values.54 The FACES pain 
scale is widely used and has demonstrated acceptable measurement properties. The tool is 
appropriate for use in children ages 3 years and older.54 
This assessment will be administered to children from 3 to 11 years of age at baseline, then daily 
through Week 6, followed by weekly to Week 24. 
7.2.3 
PROMIS Parent Proxy Pain Behavior Short Form (8a) 
The PROMIS is a system of highly reliable, precise measures of patient-reported health status for 
physical, mental, and social well-being. These tools can be used as primary or secondary endpoints 
in clinical studies of the effectiveness of treatment and can be used across a wide variety of chronic 
diseases and conditions and in the general population.  
Pain behaviors, such as verbal complaints of pain and suffering, non-language sounds, facial 
expressions, body posturing and gesturing, and limitations in activities, demonstrate to others that 
an individual is experiencing pain. The PROMIS Parent Proxy Pain Behavior item bank contains 
39 items specific to pain behaviors. From this item bank, a short form (8a) was developed specific 
to caregiver reports and consists of 8 pain behaviors assessed across a 6-point scale from “had no 
pain” to “almost always.”55 
This assessment will be administered to caregivers of children <3 years of age and will be 
performed at baseline, then daily through Week 6, followed by weekly to Week 24.  

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7.2.4 
Pain Medication Log 
A pain medication log will be kept for all participants. While participants are hospitalized, the log 
will be completed by study staff. While participants are not hospitalized, they (or their parents or 
other caregivers) will enter their medication information into the log. Pain medications and 
antispasmodics will be collected in the log. 
These assessments will be administered at baseline and then daily through Week 6 followed by 
weekly to Week 24.  
7.2.5 
Urinary Frequency and Nocturia Items from the Interstitial Cystitis Symptoms Index  
The ICSI and Interstitial Cystitis Problem Index (ICPI) are 2 brief, self-reported assessments 
designed to be utilized together to assess lower urinary tract symptoms and problems in 
participants with interstitial cystitis.56 These measures are widely used and well established with 
acceptable measurement properties. In this study, only items 2 and 3 from the ICSI will be 
administered. These items assess urinary frequency (During the past 7 days, have you had to 
urinate less than 2 hours after you finished urinating?) and nocturia (During the past 7 days, how 
often did you most typically get up at night to urinate?). The ICPI will not be administered.  
This item will be administered to participants ≥12 years of age at baseline, weekly through Week 6, 
and then at Weeks 8, 12, 16, and 24. It has been adapted to capture symptoms over the preceding 
7 days, rather than over the preceding month. In the event that the participant has an indwelling 
urinary catheter (including a 3-way catheter for continuous bladder irrigation), for the duration of 
catheterization this item will not be administered. 
7.2.6 
Age-Appropriate Global Impression Scales 
The PGIC and CGIC scales consist of 1 question each to be completed by either the participant or 
the caregiver, respectively, to assess the overall change in HC symptoms. The PGIS and CGIS 
consist of 1 question each to be completed by either the participant or the caregiver, respectively, 
to assess overall severity of symptoms. 
Age-appropriate versions of the PGIC will be administered to those 8 to 11 years of age, and 
≥12 years of age. Age-appropriate versions of the PGIS will be administered to those 3 to 7 years 
of age, 8 to 11 years of age, and 12 years of age. The CGIC will be administered to caregivers of 
children <8 years of age. The CGIS will be administered to children <3 years of age. 
The PGIS and CGIS will be administered at baseline, daily through Week 6, and then weekly to 
Week 24. The PGIC and CGIC will be administered starting on the day of the first infusion, daily 
through Week 6, and then weekly to Week 24. 
7.2.7 
EQ-5D-5L, EQ-5D-Y, and EQ-5D-Y Proxy Version 1 
The EQ-5D is a group of instruments that was developed to assess patient-reported health-related 
quality of life.57 The EQ-5D-5L includes the EQ-5D descriptive system and the EQ visual analog 
scale (EQ VAS). The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. In the EQ-5D-5L, each dimension has 5 levels: 
no problems, slight problems, moderate problems, severe problems, and extreme problems. The 
participant is asked to indicate his or her health state by checking the box next to the most 

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appropriate statement in each of the 5 dimensions. The versions used in children have 3 responses 
to each question instead of 5. 
In this study, the EQ-5D-5L will be used for individuals ≥12 years of age, the EQ-5D-Y for 
children 8 to 11 years of age, and the EQ-5D-Y Proxy Version 1 for children ≤7 years of age. Data 
for children <4 years of age will also be collected using the EQ-5D-Y Proxy Version 1, but these 
results will be analyzed separately from the results for children 4 to 7 years of age. 
The EQ-5D-5L, the EQ-5D-Y, and the EQ-5D-Y Proxy Version 1 include the EQ VAS. The EQ 
VAS records the participant’s self-rated health on a vertical visual analog scale, where the 
endpoints are labeled “The best health you can imagine” and “The worst health you can imagine.”  
These assessments will be administered at baseline, weekly through Week 6, and then at Weeks 8, 
12, 16, and 24. 
7.2.8 
Planned Exit Interview 
Approximately 35 participants at selected sites in countries where English is the primary language 
may provide additional informed consent to participate in a single participant interview. The 
interview may be conducted via telephone and will take place approximately 10 days following 
the Week 24/Early Termination visit and following participant discharge from the hospital (if 
applicable).  
Participant interviews will be conducted over the telephone by highly trained interviewer(s) from 
Research Triangle Institute Health Solutions, Research Triangle Park, NC 27709, USA utilizing a 
semi-structured interview guide developed in collaboration with AlloVir. 
The participant interview is designed to examine the experience of HC from the perspective of 
participants and caregivers of pediatric participants, including perceptions of symptom severity 
and variability, symptom burden, and disease-related impacts, as well as experiences during this 
clinical study. Participants will also be asked to provide their thoughts about the magnitude of 
meaningful changes on selected COAs utilized in the study. The participant interview will take 
approximately 60 minutes. Any adverse event(s) mentioned by a participant or caregiver during 
the interview will be captured by the interviewer and communicated to the site within the same 
business day to enable site staff to follow up and report as per protocol requirements. 
A detailed description of the participant interview and all related procedures is provided in the 
Patient Interview Procedures Guide that will be provided separately to the sites. 
7.3 
Resolution of Viral Infections 
In participants with concomitant viral infections at the time of treatment, peripheral blood and, 
where relevant, urine, will be monitored for BKV, AdV, CMV, HHV-6, JCV, and/or EBV viral 
load (Appendix A). Resolution of viral infection will be defined as a return to normal range as 
defined by the assay used and complete resolution of clinical signs and symptoms as determined 
by the Investigator.  
Samples for viral sequence/genotype will be collected on all participants as indicated in 
Appendix A. 

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8 
SAFETY ASSESSMENTS 
The safety endpoints for this study include the following: 
• Incidence and severity of acute GVHD (secondary endpoint) (for the acute GVHD grading 
scale, see Appendix E) 
• Incidence and severity of chronic GVHD (exploratory endpoint) (for the chronic GVHD 
grading scale, see Appendix E) 
• Incidence and severity of CRS (secondary endpoint) (for the CRS grading scale, see 
Appendix F) 
Safety will be evaluated throughout the duration of the study as indicated in Appendix A. 
8.1 
Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment. An adverse event can therefore be any unfavorable and/or unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of an investigational medicinal product, whether or not related to the investigational medicinal 
product. All adverse events, including observed or volunteered problems, complaints, or 
symptoms, are to be recorded on the appropriate eCRF. 
Adverse events, which include clinical laboratory test variables, will be monitored and 
documented from informed consent until study participation is complete or until resolution, 
whichever is sooner. For participants who screen fail, only SAEs will be collected (see Section 4.5 
for details). Participants should be instructed to report any adverse event that they experience to 
the Investigator, whether or not they think the event is due to study treatment. Beginning at 
informed consent, Investigators should make an assessment for adverse events at each visit and 
record each event on the appropriate adverse event eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate adverse event on the eCRF. 
Additionally, the condition that led to a medical or surgical procedure (eg, surgery, endoscopy, 
tooth extraction, or transfusion) should be recorded as an adverse event, not the procedure itself.  
Any medical condition already present at informed consent should be recorded as medical history 
and not be reported as an adverse event unless the medical condition or signs or symptoms present 
at baseline increase in severity, frequency, or seriousness at any time during the study. In this case, 
it should be reported as an adverse event. 
Clinically significant abnormal laboratory or other examination (eg, electrocardiogram [ECG]) 
findings that are detected during the study or are present at randomization and significantly worsen 
during the study should be reported as adverse events, as described below. The Investigator will 
exercise his or her medical and scientific judgment in deciding whether an abnormal laboratory 
finding or other abnormal assessment is clinically significant. Clinically significant abnormal 
laboratory values occurring during the clinical study will be followed until repeat tests return to 
normal, stabilize, or are no longer clinically significant. Abnormal test results that are determined 

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to be an error should not be reported as an adverse event. Laboratory abnormalities or other 
abnormal clinical findings (eg, ECG abnormalities) should be reported as an adverse event if any 
of the following are applicable: 
• If an intervention is required as a result of the abnormality 
• If action taken with the study drug is required as a result of the abnormality 
• Based on the clinical judgment of the Investigator 
The relevant AE, abnormality, or SAE should be followed to the point of resolution or until the 
event is considered stable, clinical insignificant, or asymptomatic. 
If the home health provider identifies or records any new or updated signs or symptoms, the 
Investigator should be notified immediately.  
8.1.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product means that a causal 
relationship between a medicinal product and an adverse event is at least a reasonable possibility, 
ie, the relationship cannot be ruled out. Section 8.1.3 provides further guidance on assessing the 
causal relationship between an adverse event and the medicinal product. 
8.1.2 
Unexpected Adverse Drug Reaction 
An unexpected adverse drug reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information. For PSL, the reference safety 
information is included in the safety review in Section 7 of the IB currently in force. The reference 
safety information will be reviewed yearly, and the periodicity of the review will be harmonized 
with the reporting period of the Development Safety Update Report.  
8.1.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each adverse event and will also categorize 
each adverse event as to its potential relationship to study drug using the categories of yes or no. 
Assessment of Severity 
The severity of all adverse events will be graded according to CTCAE version 5.0. For those 
adverse event terms not listed in the CTCAE, the following grading system should be used: 
• CTCAE Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
• CTCAE Grade 2: Moderate; minimal local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
• CTCAE Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living 
• CTCAE Grade 4: Life-threatening consequences; urgent intervention indicated 
• CTCAE Grade 5: Death related to the adverse event 

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Causality Assessment 
The relationship of an adverse event to the administration of the study drug is to be assessed 
according to the following definitions: 
No (not related, unlikely to be related) – The time course between the administration of study drug 
and the occurrence or worsening of the adverse event rules out a causal relationship and another 
cause (concomitant drugs, therapies, complications, etc.) is suspected. 
Yes (possibly, probably, or certain to be related) – The time course between the administration of 
study drug and the occurrence or worsening of the adverse event is consistent with a causal 
relationship and no other cause (concomitant drugs, therapies, complications, etc.) can be 
identified. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 
The following factors should also be considered: 
• The temporal sequence from study drug administration- 
The event should occur after the study drug is given. The length of time from study drug 
exposure to event should be evaluated in the clinical context of the event. 
• Underlying, concomitant, intercurrent diseases- 
Each report should be evaluated in the context of the natural history and course of the disease 
being treated and any other disease the participant may have. 
• Concomitant drug- 
The other drugs the participant is taking or the treatment the participant receives should be 
examined to determine whether any of them might be recognized to cause the event in question. 
• Known response pattern for this class of study drug- 
Clinical and/or preclinical data may indicate whether a particular response is likely to be a 
class effect. 
• Exposure to physical and/or mental stresses- 
The exposure to stress might induce adverse changes in the recipient and provide a logical and 
better explanation for the event. 
• The pharmacology and pharmacokinetics of the study drug- 
The known pharmacologic properties (absorption, distribution, metabolism, and excretion) of 
the study drug should be considered. 
Serious adverse events will be reviewed by the Sponsor Medical Monitor, in consultation and with 
the global safety physician and further queries issued, if necessary. If there is a disagreement 
between the Investigator and the Sponsor’s Medical Monitor regarding the designation of an event 
as serious (in line with the appropriate protocol definition), and/or regarding the plausibility of 
causality of an adverse event, the case will be referred to the DSMB for adjudication. Relevant 
information will be provided to the DSMB in parallel with the reports prepared for the next planned 

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data review meeting for evaluation at that meeting. Until the DSMB issues its response, the 
Investigator's designation will be respected.  
8.1.4 
Adverse Events of Special Interest 
The Investigator will monitor each participant for clinical and laboratory evidence for pre-defined 
AESI throughout participation in this study.  
The Investigator will assess and record any additional information on the AESI in detail on an 
adverse event form, which must be submitted within 24 hours of awareness of the event. 
For this study, AESI include the following: 
• Acute and chronic GVHD (new onset or worsening of existing GVHD) (for the acute and 
chronic GVHD grading scales, see Appendix E). 
• Graft failure and rejection. 
• CRS (for the CRS grading scale, see Appendix F). 
• Infusion-related adverse events. 
During the study, additional AESI may be identified by the Sponsor. 
Adverse events of special interest must be recorded in the eCRF. 
8.2 
Serious Adverse Events 
An adverse event or adverse reaction is considered serious if, in the view of either the Investigator 
or Sponsor, it results in any of the following outcomes: 
• Death. 
• A life-threatening adverse event. 
Note: An adverse event or adverse reaction is considered “life-threatening” if, in view of either 
the Investigator or Sponsor, its occurrence places the participant at immediate risk of death. It 
does not include an event that, had it occurred in a more severe form, might have caused death. 
• Requires hospitalization or prolongation of existing hospitalizations. 
Note: Any hospital admission with at least 1 overnight stay will be considered an inpatient 
hospitalization. An emergency room or urgent care visit without hospital admission will not 
be recorded as an SAE under this criterion, nor will hospitalization for a procedure scheduled 
or planned before signing of informed consent, or elective treatment of a pre-existing condition 
that did not worsen from baseline. However, unexpected complications and/or prolongation of 
hospitalization that occur during elective surgery should be recorded as adverse events and 
assessed for seriousness. Admission to the hospital for social or situational reasons (ie, no place 
to stay, live too far away to come for hospital visits, respite care) will not be considered 
inpatient hospitalizations.  
• A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions. 
• A congenital anomaly/birth defect. 

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• An important medical event. 
Note: Important medical events that do not meet any of the above criteria may be considered 
an SAE when, based upon appropriate medical judgment, they may jeopardize the participant 
and may require medical or surgical intervention to prevent one of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalizations, or the development of drug dependency. 
Note: Events of progression of a participant’s underlying cancer, as well as events clearly related 
to the progression of a participant’s cancer (signs/symptoms of progression), should not be 
reported as an SAE unless the outcome is fatal during the study. If the event has a fatal outcome 
during that timeframe, the event of Progression of “Type of Cancer” must be recorded as an SAE 
with CTCAE Grade 5 (fatal) outcome indicated. Diagnosis of progression of disease or 
hospitalization due to signs and symptoms of disease progression alone should not be reported as 
an SAE. 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators 
8.3.1 
Initial Reports 
All SAEs occurring from informed consent until study participation is complete or until resolution, 
whichever is sooner, must be reported to 
 (PVSS) 
and Safety Reporting Group (SRG) within 24 hours of the knowledge of the occurrence. After 
study participation is complete, any SAE that the Investigator considers related to study drug must 
be reported to 
 and SRG or the Sponsor/designee. 
To report the SAE, complete the SAE form electronically in the Medpace ClinTrak electronic data 
capture (EDC) system for the study. When the form is completed, 
 and SRG personnel 
will be notified electronically by the EDC system and will retrieve the form. If the event meets 
serious criteria and it is not possible to access the EDC system, send an email to 
 
 and 
SRG at 
 or call the phone number listed below, and 
fax/email the completed paper SAE form to
 and SRG (contact information listed in 
Section 8.6) within 24 hours of awareness. When the EDC system becomes available, the SAE 
information must be entered within 24 hours of the system becoming available. 
8.3.2 
Follow-Up Reports 
The Investigator must continue to follow the participant until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
participant dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation 
(eg, participant discharge summary or autopsy reports) to 
 and SRG via fax or email. 
If it is not possible to access the EDC system, refer to the procedures outlined above for initial 
reporting of SAEs. 

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8.4 
Pregnancy Reporting 
If a participant becomes pregnant during the study or within the safety follow-up period defined 
in the protocol, the Investigator is to stop dosing with study drug(s) immediately.  
A pregnancy is not considered to be an adverse event or SAE; however, it must be reported to 
 and SRG within 24 hours of knowledge of the event. 
 and SRG will then 
provide the Investigator/site the Pregnancy Form for completion. The Investigator/site must 
complete this form and fax/email it back to 
 and SRG.  
If the female partner of a male participant becomes pregnant while the participant is receiving 
study drug or within the safety follow-up period defined in the protocol, the Investigator should 
notify 
 and SRG as described above.  
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the Pregnancy Follow-up Form should be completed and 
faxed/emailed to 
 and SRG. If the outcome of the pregnancy meets the criteria for 
immediate classification as an SAE (ie, postpartum complication, spontaneous abortion, stillbirth, 
neonatal death, or congenital anomaly), the Investigator should follow the procedures for reporting 
an SAE. 
8.5 
Expedited Reporting 
The Sponsor/designee will report all relevant information about SUSARs that are fatal or 
life-threatening as soon as possible to the FDA, applicable competent authorities in all the Member 
States concerned, and the Central Ethics Committee, and in any case no later than 7 days after 
knowledge by the Sponsor/designee of such a case. Relevant follow-up information will 
subsequently be communicated within an additional 8 days.  
All other SUSARs will be reported to the FDA, applicable competent authorities in all the Member 
States concerned, and the Central Ethics Committee as soon as possible but within a maximum of 
15 days of first knowledge by the Sponsor/designee.  
The Sponsor/designee will also report any additional expedited safety reports required in 
accordance with the timelines outlined in country-specific legislation.  
The Sponsor/designee will also inform all Investigators as required per local regulation. 
The requirements above refer to the requirements relating to the investigational medicinal product. 
8.6 
Special Situation Reports 
Special situation reports include reports of overdose, misuse, abuse, medication error, and reports 
of adverse reactions associated with product complaints. 
• Overdose: Refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively (accidentally or intentionally), which is above the maximum 
recommended dose according to the protocol. Clinical judgement should always be applied. In 
cases of a discrepancy in the drug accountability, overdose will be established only when it is 
clear that the participant has taken additional dose(s) or the Investigator has reason to suspect 
that the participant has taken additional dose(s).  

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• Misuse: Refers to situations where the medicinal product is intentionally and inappropriately 
used in a way that is not in accordance with the protocol instructions or local prescribing 
information and may be accompanied by harmful physical and/or psychological effects.  
• Abuse: Is defined as persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects. 
• Medication error: Is any unintentional error in the prescribing, dispensing, or administration 
of a medicinal product by a healthcare professional, participant, or consumer, respectively. The 
administration or consumption of the unassigned treatment and administration of an expired 
product are always reportable as medication errors; cases of participants missing doses of study 
treatment (PSL or placebo) are not considered reportable as medication errors. 
• Product complaint: Is defined as any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug or device after it is released for distribution. A Special Situations Report 
Form will only be completed if a complaint is associated with an adverse drug reaction.  
All special situation events as described above must be reported on using the SAE form and 
faxed/emailed to 
 and SRG (contact information listed below) within 24 hours of 
knowledge of the event. All adverse events associated with these Special Situations Report Form 
should be reported as adverse events or SAEs as well as recorded on the adverse event eCRF and/or 
the SAE report form. Details of the symptoms and signs, clinical management, and outcome should 
be provided, when available. 
Safety Contact Information: 
 (PVSS) and Safety 
Reporting Group (SRG): 
Telephone (within US): 
 
Telephone (outside US): 
 
Fax: 
 
Email:
 
8.7 
Clinical Laboratory Evaluations 
Central or local laboratory results including those obtained as standard of care may be used to 
determine eligibility. Blood samples from Day 0 (pre-infusion baseline) and onward must be 
collected for analysis at the central laboratory as indicated in Appendix A. See Appendix D for a 
complete list of analytes and Appendix C for blood draw volumes and time points based on the 
participant’s weight.  
Urine will be obtained as indicated in Appendix A and sent to each site’s clinical laboratory per 
institutional guidelines for urinalysis. See Appendix D for a complete list of analytes. For RBC 
quantitation on urinalysis, some local clinical laboratories have an upper limit of RBC quantitation 
below 100 RBCs/HPF (eg, >25 RBCs/HPF, >50 RBCs/HPF). In these cases, if the urine is not 
grossly bloody on visual assessment, urine samples will be sent to the central laboratory for urine 
microscopy.  
A serum pregnancy test will be performed at screening for all participants of childbearing potential. 
A urine or serum pregnancy test must be performed <24 hours before each infusion and at the end 
of study visit for participants of childbearing potential. A negative result must be confirmed prior 

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to administration of each infusion. These tests may be performed at the local laboratory. See 
Appendix A.  
Samples for testing of viral DNA and of short sequences of T-cell receptor DNA to evaluate for 
virus-specific T-cell persistence may be retained for up to 10 years. 
8.8 
Vital Signs 
Vital sign measurements will include body temperature, blood pressure, heart rate, and respiration 
rate. Following the infusions of study treatment on Day 0 and Day 14 (±3 days), vital signs will 
be monitored after the final flush has been administered (or within 5 minutes thereof), and at 15, 
30, 45, and 60 minutes (±5 minutes of each of these time points) after the final flush. At every 
other study visit, they will be measured after resting for 5 minutes as indicated in Appendix A.  
8.9 
Electrocardiograms 
Standard 12-lead ECGs will be performed as indicated in Appendix A. On Day 0 and Day 14, the 
ECG should be performed within 1 hour after study treatment administration. A post-infusion ECG 
should be completed for all infusions of study treatment. 
8.10 
Physical Examinations 
Physical examinations will be performed and height and weight will be collected as indicated in 
Appendix A. The complete physical examination will be performed by the Investigator or another 
qualified member of the study team. New abnormal physical examination findings must be 
documented and will be followed by a physician or other qualified staff at the next scheduled visit.  
If home health visits are necessary, a body system assessment may be substituted in place of a 
complete physical examination.   
8.11 
Graft Versus Host Disease 
Acute and chronic GVHD will be assessed as indicated in Appendix A. If any participant develops 
GVHD, that participant may receive standard GVHD treatment at the discretion of the Investigator. 
8.11.1 
Acute Graft Versus Host Disease 
Grading of acute GVHD will be reported according to CTCAE version 5.0. In addition, staging 
and grading of acute GVHD will be reported using Mount Sinai Acute GVHD International 
Consortium guidelines. Response to treatment will be assessed as per Center for International 
Blood and Marrow Transplant Research (CIBMTR) modifications to the CIBMTR response index 
as described in Appendix E.59,60 
8.11.2 
Chronic Graft Versus Host Disease 
Grading of chronic GVHD will be reported according to CTCAE version 5.0. In addition, 
manifestations of chronic GVHD and response to treatment will be assessed as per National 
Institutes of Health consensus guidelines for chronic GVHD as described in Appendix E.61,62 

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8.12 
Cytokine Release Syndrome 
Manifestations of CRS will be assessed as per the American Society for Transplantation and 
Cellular Therapy consensus grading for CRS and neurologic toxicity associated with immune 
effector cells as described in Appendix F. Recommendations for monitoring for and management 
of CRS are provided in Appendix G. 
Posoleucel VSTs do not express a chimeric antigen receptor (CAR) and are not genetically 
modified. They therefore do not contain the engineered chimeric costimulatory moieties that may 
predispose to non-physiologic stimulation. Thus, the risk of CRS following administration of these 
VSTs is expected to be low. 
A CRS-like syndrome following administration of VSTs has been reported only rarely (in two 
patients with bulky EBV-associated lymphoma/post-transplant lymphoproliferative disease 
[PTLD])63,64 and has not been reported in other patients receiving VSTs.65 In PTLD, a rare 
condition, there is both an overwhelming viral burden and an uncontrolled proliferation of 
virus-transformed cells. It thus differs significantly from virus-associated HC. In order to avoid 
the potential for the development of CRS-like symptoms associated with bulky EBV-associated 
lymphoma, participants with uncontrolled or progressive EBV-associated PTLD are excluded 
from this study (Exclusion criterion #6). 
8.13 
Post-Infusion Monitoring 
Post-infusion monitoring will be performed as indicated in Appendix A. Participants will be 
monitored closely and must remain in the clinic for a minimum of 1 hour after the end of the 
infusion. Vital signs (including body temperature, heart rate, respiration rate, and blood pressure) 
and pulse oximetry will be measured at the end of the infusion (or within 5 minutes of completion), 
and at 15, 30, 45, and 60 minutes (±5 minutes of each of these time points) after the end of the 
infusion.  

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9 
STATISTICAL ANALYSES 
9.1 
Analysis Populations 
9.1.1 
Intent-to-Treat Population 
The ITT Population will include all randomized participants regardless of whether the participant 
actually receives PSL or placebo. Participants will be analyzed according to their randomized 
study treatment. 
9.1.2 
BK Intent-to-Treat Population 
The BK ITT Population will include participants in the ITT Population who have BKV identified 
as the cause of their HC. The primary efficacy analysis will be based on the BK ITT Population. 
A supplementary efficacy analysis will be based on the ITT Population. 
9.1.3 
Modified Intent-to-Treat Population 
The mITT Population will include all randomized participants who receive any amount of PSL or 
placebo. 
9.1.4 
BK Modified Intent-to-Treat Population 
The BK mITT Population will include participants in the mITT Population who have BKV 
identified as the cause of their HC. A supplementary efficacy analysis will be based on the 
BK mITT Population.  
9.1.5 
BK Per-Protocol Population 
The BK Per-Protocol (PP) Population will include all participants in the BK mITT Population who 
do not have any major protocol violations deemed to impact the results, as defined in the SAP.  
9.1.6 
Safety Population 
The Safety Population will include all participants who receive any amount of PSL or placebo. All 
safety analyses will be based on the Safety Population. Participants will be analyzed according to 
the treatment actually received. 
9.2 
Statistical Methods 
An SAP will be finalized before the interim analysis occurs. Any changes to the methods described 
in the final SAP will be described and justified as needed in the clinical study report. 
Summary statistics will be presented by treatment group. Unless otherwise stated, continuous 
variables will be summarized using the number of non-missing observations, arithmetic mean, 
standard deviation, median, minimum, and maximum values as descriptive statistics. Categorical 
variables will be summarized using the frequency count and the percentage of participants in each 
category as descriptive statistics. 
A gatekeeping strategy will be used to control the overall Type I error for analyses of the primary 
efficacy endpoint, the key secondary endpoint, and the first additional secondary efficacy endpoint. 

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9.2.1 
Analysis of Efficacy 
9.2.1.1 
Primary Efficacy Endpoint Analysis 
The primary endpoint is the time to resolution of macroscopic hematuria in participants with 
documented BK viruria. Resolution of macroscopic hematuria is defined as resolution to Grade 0 
or 1 on the Bedi scale47 on 2 consecutive urine assessments ≥2 days apart without continuous 
bladder irrigation or nephrostomy tubes; Grade 1 requires confirmation of resolution by urinalysis 
results of ≤100 RBCs/HPF. If a participant has nephrostomy tubes that are capped, Bedi 
assessments may be performed, including for the purpose of assessing for resolution. 
The objective is to demonstrate the superiority of PSL therapy to placebo with respect to the time 
to resolution of macroscopic hematuria. 
The primary efficacy analysis will be conducted after all participants have completed 24 weeks of 
follow up or discontinued from the study. At the primary analysis, the PSL group will be compared 
to the placebo group in the BK ITT Population using a stratified log-rank test based on the 
stratification factors at randomization. The study will be considered a success if the one-sided 
p-value from the stratified log-rank test comparing treatment to control is less than 0.0147 (reduced 
from 0.025 due to inclusion of an interim analysis based on Pocock method). A supplementary 
efficacy analysis based on the overall ITT Population will also be conducted. Time to resolution 
will be calculated from the time of randomization to the date of the first resolution of macroscopic 
hematuria (see Section 7.1). Participants not observed to achieve resolution will be considered 
censored at their last follow-up for the primary endpoint. Definitive therapies to stop bladder 
bleeding, such as cystectomy, bladder vessel embolization, cauterization, application of fibrin 
“glue” preparations, or formalin instillation are permitted but will be considered treatment failures 
for the primary endpoint of time to resolution of macroscopic hematuria and will be censored at 
24 weeks. The detailed censoring rules will be specified in the SAP. 
A supportive analysis of the primary efficacy endpoint will also be conducted, using a Cox 
proportional hazards model in order to account for additional potential confounders of the 
treatment effect. The Cox model will include fixed effect terms for randomized treatment 
assignment, the randomization stratification factors, concomitant antiviral use, and concomitant 
systemic corticosteroid use.  
In addition, analysis of the primary efficacy endpoint will also be performed based on the BK 
mITT and BK PP Populations as sensitivity analyses. Subgroup analyses will be conducted to 
compare responses in participants with BKV viruria <107 copies/mL to those with BK viruria 
107 copies/mL, and to evaluate responses in participants who receive concomitant antiviral 
therapies to those who do not receive these therapies during the study. 
If the result of the primary efficacy endpoint (ie, time to resolution of macroscopic hematuria) is 
statistically significant based on the BK ITT Population, a formal hypothesis test will be conducted 
sequentially of this same endpoint based on the overall ITT Population using a 0.025 significance 
level, rather than the Pocock-adjusted 0.0147 significance level used for the primary analysis based 
on the BK ITT Population. A sensitivity analysis will also be conducted based on the overall mITT 
Population. 

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9.2.1.2 
Key Secondary Efficacy Analysis 
The key secondary endpoint is the time to resolution of bladder pain as measured by 
age-appropriate COAs. Resolution of pain is defined as participants achieving a score on the 
relevant COA that does not exceed “mild pain” (defined in Section 7) without use of prescription 
pain medications or supportive bladder care. 
If the result of the analyses of the primary efficacy endpoint (ie, time to resolution of macroscopic 
hematuria) is statistically significant based on both the BK ITT and overall ITT Populations, a 
formal hypothesis test will be conducted sequentially of the time to resolution of bladder pain 
based on the BK ITT Population in the same manner as described for the primary efficacy analysis 
of the primary efficacy endpoint, except that a 0.025 significance level will be used. Additional 
analyses of the time to resolution of bladder pain will also be performed based on the BK mITT 
and BK PP Populations as sensitivity analyses.  
If this result of the analysis of time to resolution of bladder pain based on the BK ITT Population 
is statistically significant, a formal hypothesis test of this endpoint will then be conducted based 
on the overall ITT Population using a 0.025 significance level. A sensitivity analysis will be 
conducted based on the mITT Population. 
9.2.1.3 
Other Efficacy Analysis 
If the result of the key secondary efficacy analyses based on the BK ITT and overall ITT 
Populations are both statistically significant, a formal hypothesis test will be conducted 
sequentially of the first other secondary endpoint, number of days in the hospital, based on the BK 
ITT Population. The analysis will be performed using a linear regression model with terms for 
treatment and the stratification factors at randomization. This secondary endpoint will be tested at 
the one-sided 0.025 alpha level. Sensitivity analyses will be performed based on the BK mITT and 
BK PP Populations. 
If the result of the analysis based on the BK ITT Population is statistically significant, a formal 
hypothesis test of this endpoint will be conducted based on the overall ITT Population using a 
0.025 alpha level. A sensitivity analysis will be conducted using the mITT Population. 
The sequential testing described above will control the overall Type I error for these endpoints at 
the one-sided 0.025 level. 
Other continuous and categorical efficacy endpoints (including secondary and exploratory 
endpoints not selected for hierarchical testing above) will be summarized descriptively by 
treatment groups using appropriate populations. Categorical endpoints will be summarized using 
the number and percentage of participants within each category. 
Time-to-event endpoints will be summarized using Kaplan-Meier estimates. In addition, the 
hazard ratio along with the 95% confidence intervals for the true hazard ratio will be calculated 
using a Cox proportional hazards model with treatment, stratification factors at randomization, and 
other potentially confounding factors. 
There is no adjustment for multiplicity in the analyses of these other efficacy endpoints. 

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9.2.2 
Analysis of Safety 
The safety profile will be based on treatment-emergent adverse events (TEAEs) and changes in 
vital signs, physical examinations, clinical laboratory assessments, and ECGs. All safety analyses 
will be based on the Safety Population. 
Safety analyses in general will be descriptive and will be presented by phase and treatment group 
in tabular format. Categorical endpoints will be summarized using the number and percentage of 
participants within each category. Continuous endpoints will be summarized descriptively with 
summary statistics (number, mean, standard deviation, standard error, median, first quartile, third 
quartile, minimum, and maximum). 
A TEAE is defined as an adverse event with onset after the start of study treatment (PSL or 
placebo). The number and percentage of participants with TEAEs will be tabulated by MedDRA 
System Organ Class and Preferred Term for each treatment group and by severity and relationship 
to treatment. Adverse events leading to discontinuation of the study and SAEs will be summarized 
by treatment group. By-participant listings will also be provided for any deaths, SAEs, and adverse 
events leading to discontinuation of the study. 
The key safety endpoint for this study is the incidence and severity of acute GVHD. The incidence 
and severity of acute GVHD, chronic GVHD, and CRS, and the corresponding exact binomial 
confidence intervals with 95% confidence level will be presented by treatment group.  
Descriptive statistics will be provided for clinical laboratory data, vital sign data, and ECG 
parameters, presented as both actual values and changes from baseline over time. Abnormal 
physical examination findings will be presented in a by-participant data listing. 
9.2.3 
Interim Analysis 
An interim analysis will be conducted by an independent unblinded statistician and reviewed by 
the independent DSMB. This analysis will be based on primary efficacy endpoint data for the first 
60 participants randomized in the BK ITT Population. The interim analysis will be for purposes 
of potentially stopping early for success and for futility. If the study is not stopped based on the 
interim analysis, then accrual to the study will continue until there are 105 participants in the BK 
ITT Population.  
9.2.3.1 
Interim Analysis for Stopping Early for Success 
The interim analysis for stopping early for success will be performed based on the primary efficacy 
endpoint using the method of Pocock. At the interim analysis, if the one-sided p-value from the 
stratified log-rank test comparing treatment to control is less than 0.0147 (overall alpha = 0.025 
adjusted for the interim analysis), the study will be stopped early for success. If the study is stopped 
early for success based on the primary efficacy endpoint, the key secondary efficacy endpoints and 
the first other secondary efficacy endpoint will be tested sequentially as described above using a 
one-sided 0.025 alpha level. 
9.2.3.2 
Interim Analysis for Futility 
The interim analysis for futility will also be based on the primary efficacy endpoint. The decision 
to stop for futility is based on the conditional probability that the study will be successful should 
it continue to the sample size of 105 participants in the BK ITT Population with participants being 
followed for 24 weeks. The calculation will assume that the final analysis will be a log-rank test 

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conducted at the one-sided 0.0147 level. If, at the interim analysis, the conditional probability of 
study success with 105 BK ITT Population participants falls below 5%, the study will stop early 
for futility. Enrollment and participant follow-up will then be discontinued, and the final analyses 
will be conducted. The futility stopping in this study is considered non-binding. 
9.2.4 
Sample Size Determination 
Approximately 125 participants will be randomized at approximately 90 clinical sites to achieve 
105 participants in the BK ITT Population (the primary efficacy analysis population), assuming 
85% of randomized participants will be included in the BK ITT Population. Enrollment in the 
study will continue until there are 105 participants in the BK ITT Population. Participants will be 
randomized in a 
ratio to receive PSL or placebo. Assuming the median times to resolution for 
the placebo arm and the PSL arm are, respectively, 12 weeks and 6 weeks; time to resolution 
follows an exponential distribution; 24 weeks of follow-up; use of a log-rank test; one interim 
analysis based on the method of Pocock; control of the overall Type I error rate at the one-sided 
0.025 level; 10% of participants are censored for losses to follow-up or dropout by 24 weeks; time 
to censoring follows an exponential distribution and is equivalent in the two arms, the study will 
have 83.8% power. 

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10 
DATA MANAGEMENT AND RECORD KEEPING 
10.1 
Data Management 
10.1.1 
Data Handling 
Data will be recorded at the sites on eCRFs and reviewed by the Clinical Research Associate 
(CRA) during monitoring visits. The CRAs will verify data recorded in the EDC system with 
source documents. All corrections or changes made to any study data must be appropriately tracked 
in an audit trail in the EDC system. An eCRF will be considered complete when all missing, 
incorrect, and/or inconsistent data have been accounted for. 
10.1.2 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory requirements. 
10.1.3 
Data Entry 
Data must be recorded using the EDC system while the study is in progress. All site personnel 
must log into the system using their secure username and password in order to enter, review, or 
correct study data. These procedures must comply with Title 21 of the CFR (21 CFR Part 11) and 
other appropriate international regulations. All passwords will be strictly confidential. 
10.1.4 
Medical Information Coding 
For medical information, the following thesauri will be used: 
• Medical Dictionary for Regulatory Activities (latest) for medical history and adverse events 
• World Health Organization Drug Dictionary for prior and concomitant medications 
10.1.5 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the investigative site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 
10.2 
Record Keeping 
Records of participants, source documents, monitoring visit logs, eCRFs, inventory of study 
product, regulatory documents, and other Sponsor correspondence pertaining to the study must be 
kept in the appropriate study files at the site. Source data are defined as all information in original 
records and certified copies of original records of clinical findings, observations, or other activities 
in a clinical study necessary for the evaluation and reconstruction of the clinical study. Source data 
are contained in source documents (original records or certified copies). These records will be 
retained in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer 
or destruction of these records, the Sponsor must be notified in writing and be given the 
opportunity to further store such records.  

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10.3 
End of Study 
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last participant in the study or when the 
Sponsor receives the last laboratory result, whichever comes last. 

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11 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL  
11.1 
Ethical Conduct of the Study 
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve human participants. Compliance with 
this standard provides public assurance that the rights, safety, and well-being of study participants 
are protected, consistent with the principles that have their origin in the Declaration of Helsinki, 
and that the clinical study data are credible. 
11.2 
Institutional Review Board/Independent Ethics Committee 
11.2.1 
Institutional Review Board 
The IRB will review all appropriate study documentation in order to safeguard the rights, safety, 
and well-being of participants. The study will only be conducted at sites where IRB approval has 
been obtained. The protocol, IB, ICF/assent form, advertisements (if applicable), written 
information given to the participants, safety updates, annual progress reports, and any revisions to 
these documents will be provided to the IRB by the Investigator. 
Federal regulations and International Council for Harmonisation (ICH) Guidelines require that 
approval be obtained from an IRB prior to participation of participants in research studies. Prior 
to study onset, the protocol, any protocol amendments, ICFs/assent forms, advertisements to be 
used for participant recruitment, and any other written information regarding this study to be 
provided to a participant or participant’s legal guardian must be approved by the IRB. 
No drug will be released to the site for dosing until written IRB authorization has been received 
by the Sponsor. 
11.2.2 
Independent Ethics Committee 
It is the responsibility of the Sponsor or their designee (ie, Medpace) to obtain the approval of the 
responsible ethics committees according to the national regulations.  
The study will only start in the respective sites once the respective committee’s written approval 
has been given. 
11.3 
Informed Consent 
Prior to conducting any study-related activities, written informed consent to participate in the study 
must be provided by the participant, or a parent or legal guardian must provide written informed 
consent and the potential pediatric participant must provide assent in a manner approved by the 
IRB/IEC and local regulations. 
The ICF (and assent form, if applicable) and any changes to the ICF/assent form made during the 
course of the study must be agreed to by the Sponsor or designee and the IRB/IEC prior to its use 
and must be in compliance with all ICH GCP, local regulatory, and legal requirements.  
The Investigator must ensure that each study participant is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
participant has been informed of his/her rights to privacy. The Investigator will obtain written 
informed consent from each participant, or the participant’s parent/legal guardian and assent from 

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the potential pediatric participant, before any study-specific activity is performed and should 
document in the source documentation that consent was obtained prior to enrollment in the study. 
The original signed copy of the ICF/assent form must be maintained by the Investigator and is 
subject to inspection by a representative of the Sponsor, their representatives, auditors, the IRB, 
and/or regulatory agencies. A copy of the signed ICF/assent form will be given to the participant 
and his/her parent/legal guardian when applicable. 
Note that there is a separate consent form for participants in the optional Pre-Screening Visit (see 
Section 4.4). 
11.4 
Subject Card 
Upon enrollment in the study, the participant will receive a subject card to be carried at all times. 
The subject card will state that the participant is in a clinical research study, type of treatment, and 
contact details in case of an SAE. 
11.5 
Study Monitoring Requirements 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, Declaration of Helsinki, ICH GCP, Directive 2001/20/EC, and applicable regulatory 
requirements, and that valid data are entered into the eCRFs. 
To achieve this objective, the monitor’s duties are to aid the Investigator and, at the same time, the 
Sponsor, in the maintenance of complete, legible, well organized, and easily retrievable data. 
Before the enrollment of any participant in this study, the Sponsor or their designee will review 
with the Investigator and site personnel the following documents: protocol, IB, eCRFs and 
procedures for their completion, informed consent/assent process, and the procedure for reporting 
SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data are 
entered by the site, the CRA will review the data for safety information, completeness, accuracy, 
and logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
Investigators. The Investigator and his/her staff will be expected to cooperate with the monitor and 
provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
11.6 
Disclosure of Data 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB/IEC as appropriate. Participants or 
their legal representatives may request their medical information be given to their personal 
physician or other appropriate medical personnel responsible for their welfare. 
Participant medical information obtained during the study is confidential and disclosure to third 
parties other than those noted above is prohibited. 

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11.7 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participants (sufficient information to link records, 
eg, eCRFs and hospital records), all original signed ICFs/assent forms, copies of all eCRFs, SAE 
forms, source documents, and detailed records of treatment disposition. The records should be 
retained by the Investigator according to specifications in the ICH Guidelines, local regulations, 
or as specified in the Clinical Study Agreement, whichever is longer. The Investigator must obtain 
written permission from the Sponsor before disposing of any records, even if retention 
requirements have been met. 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor.  
11.8 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal and/or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 
11.9 
Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 CFR Part 54. In addition, Investigators must commit to 
promptly updating this information if any relevant changes occur during the study and for a period 
of 1 year after the completion of the study. 
11.10 
Insurance and Indemnity 
In accordance with the relevant national regulations, the Sponsor will take out patient liability 
insurance for all participants who give their consent to the clinical study. This coverage is designed 
in the event that a fatality, physical injury, or damage to health occurs during the clinical study’s 
execution. 
11.11 
Legal Aspects 
The clinical study will be submitted to the relevant national competent authorities in all 
participating countries to achieve a clinical trial authorisation (CTA). 
The study will commence (ie, initiation of study centers) when the CTA and favorable IRB/IEC 
opinion have been received.  

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12 
STUDY ADMINISTRATIVE INFORMATION 
12.1 
Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by the Sponsor 
or designee. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB/IEC, unless immediate implementation of the change is necessary for participant safety. In 
this case, the situation must be documented and reported to the IRB/IEC within 5 working days. 
12.2 
Home Health Visits 
Home health visits may be available as an optional service that permits an appropriately trained 
and delegated HCP to conduct study procedures in the patient's home (or other convenient 
location). Home health visits may be conducted as agreed with the Sponsor.  
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13 
REFERENCES 
1. Dosin G, Aoun F, El Rassy E, et al. Viral-induced hemorrhagic cystitis after allogeneic 
hematopoietic stem cell transplant. Clin Lymphoma Myeloma Leuk. 2017;17(7):438-42. 
2. Lynch JP 3rd, Kajon AE. Adenovirus: epidemiology, global spread of novel serotypes, and 
advances in treatment and prevention. Semin Respir Crit Care Med. 2016;37(4):586 602. 
3. Furukawa R, Homma H, Inoue T, et al. Cytomegalovirus hemorrhagic cystitis in a malignant 
glioma patient treated with temozolomide. Intern Med. 2018;57(20):3047 50. 
4. Franzén J, Ramqvist T, Bogdanovic G, et al. Studies of human polyomaviruses, with HPyV7, 
BKPyV, and JCPyV present in urine of allogeneic hematopoietic stem cell transplanted 
patients with or without hemorrhagic cystitis. Transpl Infect Dis. 2016;18(2):240-6.  
5. Slade M, Goldsmith S, Romee R, et al. Epidemiology of infections following haploidentical 
peripheral blood hematopoietic cell transplantation. Transpl Infect Dis. 2017;19(1):e12629. 
6. Voigt S, Pochon C, Rao K, et al. Incidence of adenovirus infections in pediatric and adult 
allogeneic hematopoietic cell transplant recipients in Europe. Presentation, 2018 March, 
European Society 
for Blood 
Marrow Transplantation 
Meeting. Chimerix, 
Inc. 
http://www.chimerix.com/wp-content/uploads/2018/03/EBMT2018_Voigt-et-al_AdVance-
AdV-Incidence-Presentation.pdf. Accessed 09 Nov 2020. 
7. Zecca M, Rao K, Pérez-Martínez A, et al. Adenovirus viral burden is associated with mortality 
in pediatric allogeneic hematopoietic cell transplant recipients: results from the AdVance 
study. Presentation, 2018 March, European Society for Blood Marrow Transplantation 
Meeting. 
Chimerix, 
Inc. 
http://www.chimerix.com/wp-
content/uploads/2018/03/EBMT2018_Zecca-et-al_AdVance-AdV-Outcomes-
Presentation.pdf. Accessed 09 Nov 2020. 
8. Crocchiolo R, Bramanti S, Vai A, et al. Infections after T-replete haploidentical transplantation 
and high-dose cyclophosphamide as graft-versus-host disease prophylaxis. Transpl Infect Dis. 
2015;17(2):242-9. 
9. Gilis L, Morisset S, Billaud G, et al. High burden of BK virus-associated hemorrhagic cystitis 
in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow 
Transplant. 2014;49(5):664-70. 
10. Kurtz M, Feldman AS, Perazella MA. Etiology and evaluation of hematuria in adults. 
UpToDate®. 
https://www.uptodate.com/contents/etiology-and-evaluation-of-hematuria-in-
adults#H3. Accessed 09 Nov 2020. 
11. Abudayyeh A, Hamdi A, Abdelrahim M, et al. Poor immune reconstitution is associated with 
symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients. Transpl 
Infect Dis. 2017;19(1):e12632. 
12. Walter EA, Greenberg PD, Gilbert MJ, et al. Reconstitution of cellular immunity against 
cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the 
donor. N Engl J Med. 1995;333(16):1038-44. 
13. Peggs KS, Verfuerth S, Pizzey A, et al. Adoptive cellular therapy for early cytomegalovirus 
infection after allogeneic stem-cell transplantation with virus-specific T cell lines. Lancet. 
2003;362(9393):1375-7. 

AlloVir, Inc. 
Clinical Study Protocol AVM-003-HC 
Confidential & Proprietary 
 
Version 5.0, 23 February 2022 
76 
14. Peggs KS, Thomson K, Samuel E, et al. Directly selected cytomegalovirus-reactive donor T 
cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem 
cell transplantation. Clin Infect Dis. 2011;52(1):49-57. 
15. Mackinnon S, Thomson K, Verfuerth S, et al. Adoptive cellular therapy for cytomegalovirus 
infection following allogeneic stem cell transplantation using virus specific T cells. Blood 
Cells Mol Dis. 2008;40(1):63-7. 
16. Einsele H, Roosnek E, Rufer N, et al. Infusion of cytomegalovirus (CMV)-specific T cells for 
the treatment of CMV infection not responding to antiviral chemotherapy. Blood. 
2002;99(11):3916-22. 
17. Feuchtinger T, Opherk K, Bethge WA, et al. Adoptive transfer of pp65-specific T cells for the 
treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and 
matched unrelated stem cell transplantation. Blood. 2010;116(20):4360-7. 
18. Schmitt A, Tonn T, Busch DH, et al. Adoptive transfer and selective reconstitution of 
streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients 
after allogeneic peripheral blood stem cell transplantation. Transfusion. 2011;51(3):591-9. 
19. Cobbold M, Khan N, Pourgheysari B, et al. Adoptive transfer of cytomegalovirus specific CTL 
to stem cell transplant patients after selection by HLA peptide tetramers. J Exp Med. 
2005;202(3):379-86. 
20. Rooney CM, Smith CA, Ng CY, et al. Use of gene-modified virus-specific T lymphocytes to 
control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995;345(8941):9-13. 
21. Heslop HE, Ng CY, Li C, et al. Long-term restoration of immunity against Epstein-Barr virus 
infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med. 
1996;2(5):551-5. 
22. Leen AM, Christin A, Myers GD, et al. Cytotoxic T lymphocyte therapy with donor T cells 
prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and 
matched unrelated stem cell transplantation. Blood. 2009;114(19):4283-92. 
23. Leen AM, Myers GD, Sili U, et al. Monoculture-derived T lymphocytes specific for multiple 
viruses expand and produce clinically relevant effects in immunocompromised individuals. 
Nat Med. 2006;12(10):1160-6. 
24. Gerdemann U, Katari UL, Papadopoulou A, et al. Safety and clinical efficacy of rapidly 
generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after 
allogeneic hematopoietic stem cell transplant. Mol Therapy. 2013;21(11):2113-21. 
25. Papadopoulou A, Gerdemann U, Katari UL, et al. Activity of broad-spectrum T cells as 
treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 
2014;6(242):242ra83. 
26. Feuchtinger T, Matthes-Martin S, Richard C, et al. Safe adoptive transfer of virus specific T-
cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell 
transplantation. Br J Haematol. 2006;134(1):64-76. 
27. Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of Epstein-Barr virus (EBV) nuclear 
antigen 1-specific T cells as treatment for EBV reactivation and lymphoproliferative disorders 
after allogeneic stem-cell transplantation. J Clin Oncol. 2013;31(1):39-48. 

AlloVir, Inc. 
Clinical Study Protocol AVM-003-HC 
Confidential & Proprietary 
 
Version 5.0, 23 February 2022 
77 
28. Heslop HE, Slobod KS, Pule MA, et al. Long-term outcome of EBV-specific T-cell infusions 
to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 
2010;115(5):925-35. 
29. Bollard CM, Heslop HE. T cells for viral infections after allogeneic hematopoietic stem cell 
transplant. Blood. 2016;127(26):3331-40. 
30. O'Reilly RJ, Prockop S, Hasan AN, et al. Virus-specific T-cell banks for ‘off the shelf’ adoptive 
therapy of refractory infections. Bone Marrow Transplant. 2016;51(9):1163 72. 
31. Vera JF, Brenner LJ, Gerdemann U, et al. Accelerated production of antigen-specific T cells 
for preclinical and clinical applications using gas-permeable rapid expansion cultureware (G-
Rex). J Immunother. 2010;33(3):305-15. 
32. Gerdemann U, Keirnan JM, Katari UL, et al. Rapidly generated multivirus-specific cytotoxic 
T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther. 
2012;20(8):1622-32. 
33. Haque T, Wilkie GM, Jones MM, et al. Allogeneic cytotoxic T-cell therapy for EBV positive 
posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. 
Blood. 2007;110(4):1123-31. 
34. Haque T, Wilkie GM, Taylor C, et al. Treatment of Epstein-Barr-virus-positive post 
transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T 
cells. Lancet. 2002;360(9331):436-42. 
35. Vickers MA, Wilkie GM, Robinson N, et al. Establishment and operation of a Good 
Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell 
bank for the treatment of EBV-associated lymphoproliferative disease. Br J Haematol. 
2014;167(3):402-10. 
36. Leen AM, Bollard CM, Mendizabal AM, et al. Multicenter study of banked third-party virus-
specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. 
Blood. 2013;121(26):5113-23. 
37. Barbanti-Brodano G, Sabbioni S, Martini F, et al. BK virus, JC virus and Simian Virus 40 
infection in humans, and association with human tumors. Adv Exp Med Biol. 2006;577:319-
41. 
38. Krymskaya L, Sharma MC, Martinez J, et al. Cross-reactivity of T lymphocytes recognizing a 
human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides. J Virol. 
2005;79(17):11170-8. 
39. Li J, Melenhorst J, Hensel N, et al. T-cell responses to peptide fragments of the BK virus T 
antigen: implications for cross-reactivity of immune response to JC virus. J Gen Virol. 
2005;87:2951-60. 
40. Muftuoglu M, Olson A, Marin D, et al. Allogeneic BK virus-specific T cells for progressive 
multifocal leukoencephalopathy. N Engl J Med. 2018;379(15):1443-51. 
41. Tzannou I, Watanabe A, Naik S, et al. “Mini” bank of only 8 donors supplies CMV directed T 
cells to diverse recipients. Blood Adv. 2019;3(17):2571-80. 

AlloVir, Inc. 
Clinical Study Protocol AVM-003-HC 
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Version 5.0, 23 February 2022 
78 
42. Tzannou I, Papadopoulou A, Naik S, et al. Off-the-shelf virus-specific T cells to treat BK virus, 
human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, and adenovirus infections after 
allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2017;35(31):3547-57. 
43. European Medicines Agency and Heads of Medicines Agencies. Guidance on the management 
of clinical trials during the COVID-19 (coronavirus) pandemic - Version 3 - 28/04/2020. 
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-
10/guidanceclinicaltrials_covid19_en.pdf. Accessed on 02 Nov 2020. 
44. FDA guidance on conduct of clinical trials of medical products during COVID-19 public health 
emergency guidance for industry, investigators, and institutional review boards. March 2020; 
updated on September 21, 2020. https://www.fda.gov/media/136238/download. Accessed on 
02 Nov 2020. 
45. Ueda Oshima M, Sandmaier BM, Petersdorf E, et al. Blood and marrow transplantation during 
the emerging COVID-19 pandemic: the Seattle approach. Bone Marrow Transplant. 2020:1–
9. Epub ahead of print. 
46. GOV.UK Guidance: Managing clinical trials during Coronavirus (COVID-19). Published 19 
March 2020; last updated 16 March 2021. https://www.gov.uk/guidance/managing-clinical-
trials-during-coronavirus-covid-19#management-of-covid-19-vaccine-deployment-for-
ongoing-non-covid-19-clinical-trials. Accessed on 21 April 2021. 
47. Bedi A, Miller CB, Hanson JL, et al. Association of BK virus with failure of prophylaxis 
against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol. 
1995;13(5):1103-9. 
48. Cesaro S, Dalianis T, Hanssen Rinaldo C, et al. ECIL guidelines for the prevention, diagnosis 
and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem 
cell transplant recipients. J Antimicrob Chemother. 2018;73(1):12 21. 
49. El-Zimaity M, Saliba R, Chan K, et al. Hemorrhagic cystitis after allogeneic hematopoietic 
stem cell transplantation: donor type matters. Blood. 2004;103(12):4674 80. 
50. Laskin BL, Denburg MR, Furth SL, et al. The natural history of BK polyomavirus and the host 
immune response after stem cell transplantation. Clin Infect Dis. 2019;pii:ciz1194. doi: 
10.1093/cid/ciz1194. [Epub ahead of print]. 
51. Au JK, Graziano C, Elizondo RA, et al. Urologic outcomes of children with hemorrhagic 
cystitis after bone marrow transplant at a single institution. Urology. 2017;101:126-32. 
52. Hageman N, Aronsen T, Tiselius HG. A simple device (Hemostick®) for the standardized 
description of macroscopic haematuria: our initial experience. Scand J Urol Nephrol. 
2006;40(2):149-54. 
53. Humphrey L, Arbuckle R, Moldwin R, et al. The Bladder Pain/Interstitial Cystitis Symptom 
Score: development, validation, and identification of a cut score. Eur Urol. 2012;61(2):271-9. 
54. Wong DL, Baker CM. Pain in children: comparison of assessment scales. Pediatr Nurs. 
1988;14(1):9-17. 
55. HealthMeasures. Patient-Reported Outcomes Measurement Information System pain behavior 
scoring 
manual. 
Updated 
19 
Jul 
2019. 
http://www.healthmeasures.net/images/PROMIS/manuals/PROMIS_Pain_Behavior_Scoring

AlloVir, Inc. 
Clinical Study Protocol AVM-003-HC 
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Version 5.0, 23 February 2022 
79 
_Manual.pdf. Accessed 09 Nov 2020. 
56. O’Leary MP, Sant GR, Fowler FJ Jr, et al. The interstitial cystitis symptom index and problem 
index. Urology. 1997;49(5A Suppl):58-63. 
57. EuroQOL. EQ-5D. https://euroqol.org/. Accessed on 09 Nov 2020. 
58. HealthMeasures. 
Patient-reported 
outcomes 
measurement 
information 
system. 
http://www.healthmeasures.net/index.php?option=com_content&view=category&layout=blo
g&id=147&Itemid=806. Accessed 09 Nov 2020. 
59. Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-
versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD 
International Consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10. 
60. Center for International Blood & Marrow Transplant Research (CIBMTR). Clinical trial 
endpoints 
for 
patients 
with 
acute 
GVHD. 
May 
2009. 
https://www.cibmtr.org/Meetings/Materials/GVHDworkshop/GvHD%20Workshop%20Libra
ry/08_Alousi_FDAaGVHDwrkshp_May09.pdf. Accessed 09 Nov 2020. 
61. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development 
project on criteria for clinical trials in chronic graft-versus-host-disease: I. The 2014 Diagnosis 
and staging working group report. Biol Blood Marrow Transplant. 2015;21(3):389-401. 
62. Lee ST, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic graft versus host 
disease. Biol Blood Marrow Transplant. 2015;21(6):984-99. 
63. Papadopoulou A, Krance RA, Allen CE, et al. Systemic inflammatory response syndrome after 
administration of unmodified T lymphocytes. Molec Ther. 2014;22(6):1134-8.  
64. Rooney CM, Smith CA, Ng CY, et al. Infusion of cytotoxic T cells for the prevention and 
treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood. 
1998. 92(5): 1549–55.  
65. Simmons HZ, Bazzell AF, Dains JE. Adverse effects of virus-specific T-cell therapy: an 
integrative review. J Adv Pract Oncol. 2019;10(2):120-31.  

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APPENDIX A:  SCHEDULE OF PROCEDURES 
Study Visit/Week 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±28 
±28 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
Pre-screening informed 
consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
Informed consent/assent 
[4] 
 
X 
 
 
 
 
 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Demographics [5] 
 
X 
 
 
 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications [6] 
 
 
Adverse events [7] 
 
 
Complete physical 
examination [8] 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Height and weight [9] 
 
X 
X 
 
X 
 
 
 
 
 
X 
Vital signs and pulse 
oximetry [10] 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical outcome 
assessments [11] 
 
See Appendix B 
Documentation of HLA 
typing [5,12] 
 
X 
 
 
 
 
 
 
 
 
 
Hematology [13] 
 
X [14] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical chemistry [15]  
 
X [14] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Viral loads in urine [15] 
X 
X [14] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Viral loads in blood [13, 
15] 
 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test [16] 
 
X 
X 
 
X 
 
 
 
 
 
X 
FSH [17] 
 
X 
 
 
 
 
 
 
 
 
 

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Study Visit/Week 
Pre-
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
±28 
±28 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
Visual assessment of urine 
by Bedi grading with 
urinalysis 
 
X 
 
Inpatients: At baseline, then 3 × per week [18] through the end of Week 6 
(Day 42) or until resolution, then 1 × per week 
Outpatients: At baseline, then 1 × per week [18] through the end of Week 6 
(Day 42)  
Starting Week 7  
(Day 43): 
Inpatients: 2 × per 
week [18] ≥2 days 
apart until 
resolution, then 1 × 
per week 
Outpatients: 1 × 
per week until 
resolution, then at 
study visits 
Visual assessment of urine 
by Hemostick (outpatients 
only)  
 
 
 
At baseline, then daily through the end of  Week 6 (Day 42) or resolution 
(whichever occurs earlier), then 1 × per week 
Starting Week 7  
(Day 43): 
2 × per week ≥2 
days apart until 
resolution, then 1 × 
per week 
Collection of PBMCs for 
banking of human genetic 
DNA and plasma [13, 19] 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
Acute GVHD evaluation 
[20] 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
Chronic GVHD evaluation 
[20] 
 
 
X 
 
 
 
 
 
 
X 
X 
Randomization [21] 
 
 
X 
 
 
 
 
 
 
 
 
Distribution of subject 
cards 
 
 
X 
 
 
 
 
 
 
 
 
Study treatment 
administration [22] 
 
 
X 
 
X 
 
 
 
 
 
 
Post-infusion monitoring 
[23] 
 
 
X  
 
X 
 
 
 
 
 
 
12-Lead ECG 
 
X 
X [24] 
 
X [24] 
 
 
 
 
 
X 

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Note: Study visits should occur at the study site. If this is not possible, home health visits may be performed as agreed with the Sponsor. 
1. 
Participants may complete an optional Pre-Screening Visit that will be conducted from 14 days prior to the randomization visit to the day of the randomization visit. A separate 
Pre-Screening consent form is available for this purpose.  
2. 
All screening and baseline assessments must be performed prior to study treatment administration. 
3. 
The Day 0 samples to be sent to the central laboratory must be collected <24 hours prior to study treatment administration. Screening assessments may also be considered 
baseline assessments if they were done <24 hours prior to study treatment administration. 
4. 
Prior to conducting any study-related activities, written informed consent/assent to participate in the study must be provided by the participant and/or participant’s legal guardian. 
The Pre-Screening ICF is separate from the ICF that is signed at the Screening Visit for study participation. 
5. 
Data will be collected from all participants who consent to participate. 
6. 
Analgesic use will be collected daily on a medication log for inpatients and pain medication log within the ePRO system for outpatients. 
7. 
See Section 8.1 for details on adverse event reporting. 
8. 
If necessary, home health visits may substitute a body system assessment in place of a complete physical examination.  
9. 
Height will be measured at screening only. Weight will be assessed at the screening, baseline, Week 2, and Week 24 visits.  
10. Includes body temperature, blood pressure, heart rate, and respiration rate and will be measured after resting for 5 minutes. Pulse oximetry to be collected only on Day 0 and 
Week 2 study visits prior to study treatment administration. 
11. Participants must be trained on the clinical outcome assessments (see Appendix B) at the Screening Visit. Adherence to the required clinical outcome assessments should be 
reviewed with the participant at each study visit. 
12. The HLA types of the participant and HCT donor(s) will be obtained from the medical record.  
13. For blood sampling volumes and sampling schedule by body weight, please refer to Appendix C. 
14. Central or local laboratory results including those obtained as standard of care may be used to determine eligibility.  
15. DNA for viral sequencing/genotyping will be extracted from the blood and urine samples collected for viral load determination. In the event of viral recurrence, viral 
sequence/genotype at baseline will be compared with that at the time of recurrence. Viral DNA isolated from blood and urine samples will be stored for potential future 
sequencing/genotyping. Target viruses are BKV, AdV, CMV, HHV-6, JCV, and EBV. 
16. A serum pregnancy test will be performed at screening for all participants of childbearing potential. A urine or serum pregnancy test must be performed <24 hours before each 
infusion and at the end of study visit for participants of childbearing potential. A negative result must be confirmed prior to administration of each infusion. These tests may be 
performed at the local laboratory.  
17. FSH will be tested for women of nonchildbearing potential who are postmenopausal, defined as 12 consecutive months with no menses without an alternative medical cause. 
18. The Bedi assessment with urinalysis may be performed more frequently (as unscheduled visits) if needed to evaluate for resolution of macroscopic hematuria. 
19. Blood will be collected into a cell separation tube and processed to generate a PBMC fraction and a plasma fraction. Human genetic DNA will be extracted from the PBMC 
fraction. This will be stored for potential future evaluation of VST persistence by T-cell receptor sequencing. The plasma fraction will be stored for potential future evaluation 
of cytokines and/or other humoral markers of inflammation/immune function. 
20. If any participant develops GVHD, they may receive standard GVHD treatment at the discretion of the Investigator. Staging and grading of acute GVHD will be reported using 
MAGIC guidelines. Response to treatment will be assessed as per CIBMTR modifications to the CIBMTR response index. Manifestations of chronic GVHD and response to 
treatment will be assessed as per National Institutes of Health consensus guidelines for chronic GVHD. 
21. Randomization will occur after all eligibility criteria are met, after all screening procedures are complete, and prior to study treatment administration. 
22. All participants will receive  infusions of either PSL or placebo separated by 
. Administering the 
 as early as feasible within this window is 
encouraged. Based on body weight at screening, participants <40 kg will receive 
 
 or placebo, participants ≥40 kg will receive
 
 or placebo. As 
GVHD is a theoretical safety concern, the incidence and severity of GVHD will be monitored during the study. No participants will receive a 
 infusion (PSL or placebo) 
if they develop worsening GVHD (ie, relative to baseline GVHD) at the proposed time for infusion of the 
. 

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23. Participants will be monitored closely and must remain in the clinic for ≥1 hour after the end of study treatment administration. Vital signs, including body temperature, blood 
pressure, heart rate, and respiration rate, as well as pulse oximetry will be measured within 5 minutes after the final flush has been administered, and at 15, 30, 45, and 60 
minutes (±5 minutes of each of these time points) after the final flush.  
24. The ECG is to be performed ≤1 hour after study treatment administration. 
AdV = adenovirus; BKV = BK virus; CIBMTR = Center for International Blood and Marrow Transplant Research; CMV = cytomegalovirus; DNA = deoxyribonucleic acid; 
EBV = Epstein-Barr virus; ECG = electrocardiogram; ePRO = electronic patient-reported outcome; ET = Early Termination; FSH = follicle-stimulating hormone; GVHD = graft 
versus host disease; HCT = hematopoietic cell transplant; HHV-6 = human herpesvirus 6; HLA = human leukocyte antigen; I/E = inclusion and exclusion; JCV = JC virus; LFT = 
liver function test; MAGIC = Mount Sinai Acute GVHD International Consortium; NA = not applicable; PBMC = peripheral blood mononuclear cell; VST = virus-specific T cell. 
 
 

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APPENDIX B:  CLINICAL OUTCOME ASSESSMENTS BY AGE GROUP  
Study Week 
 
Baseline 
 
 
 
 
 
 
 
 
 
Study Day 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
 
Assessment 
Age Ranges 
(Years) [2] 
 
 
 
Children ˂3 years 
 
 
Visual assessment of urine by 
Hemostick (outpatients only) 
 
At baseline, then daily through the end of Week 6 (Day 42) or resolution 
(whichever occurs earlier), then 1 × per week 
Starting Week 7  
(Day 43): 
2 × per week ≥2 days apart 
until resolution, then 1 × per 
week  
PROMIS® Parent Proxy Pain 
Behavior Short Form 
 
X 
Daily 
Weekly to Week 24 
Pain medication log 
 
X 
Outpatient: daily by participant/caregiver 
Inpatient: daily by study staff 
Outpatient: weekly by 
participant/caregiver 
Inpatient: weekly by study 
staff 
CGIS (severity of HC)  
 
X 
Daily 
Weekly to Week 24 
CGIC (change in HC) 
 
X 
Daily 
Weekly to Week 24 
EQ-5D-Y Proxy Version 1 
[3] 
X 
Weekly 
Weeks 8, 12, 16, and 24 
Children 3 to 11 years 
 
 
Visual assessment of urine by 
Hemostick (outpatients only) 
 
At baseline, then daily through the end of Week 6 (Day 42) or resolution 
(whichever occurs earlier), then 1 × per week 
Starting Week 7  
(Day 43): 
2 × per week ≥2 days apart 
until resolution, then 1 × per 
week  
Wong-Baker FACES pain 
scale  
  
X 
Daily 
Weekly to Week 24 
Pain medication log 
 
X 
Outpatient: collected daily by participant/caregiver 
Inpatient: collected daily by study staff 
Outpatient: collected weekly 
by participant/caregiver 
Inpatient: collected weekly 

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Study Week 
 
Baseline 
 
 
 
 
 
 
 
 
 
Study Day 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
 
NA 
±3 
±3 
±3 
±3 
±3 
±3 
 
by study staff 
PGIS (severity of HC)  
[4] 
X 
Daily 
Weekly to Week 24 
CGIC/PGIC (change in HC)  
3 to 7 
(CGIC); 8 to 
11 (PGIC) 
[4] 
X 
Daily 
Weekly to Week 24 
EQ-5D-Y Proxy Version 1 
3 to 7 [3] 
X 
Weekly 
Weeks 8, 12, 16, and 24 
EQ-5D-Y  
8 to 11 
X 
Weekly 
Weeks 8, 12, 16, and 24 
Adolescents ≥12 years and adults 
 
 
Visual assessment of urine by 
Hemostick (outpatients only) 
 
At baseline, then daily through the end of Week 6 (Day 42) or resolution 
(whichever occurs earlier), then 1 × per week 
Starting Week 7  
(Day 43): 
2 × per week ≥2 days apart 
until resolution, then 1 × per 
week  
Selected BPIC SD items 
 
X 
Daily 
Weekly to Week 24 
Pain medication log  
 
X 
Outpatient: daily by participant/caregiver 
Inpatient: daily by study staff 
Outpatient: weekly by 
participant/caregiver 
Inpatient: weekly by study 
staff 
Selected ICSI items 
 
X 
Weekly 
Weeks 8, 12, 16, and 24 
PGIS (severity of HC) [4] 
 
X 
Daily 
Weekly to Week 24 
PGIC (change in HC) [4] 
 
X 
Daily  
Weekly to Week 24 
EQ-5D-5L  
 
X 
Weekly 
Weeks 8, 12, 16, and 24 
Note: For participants for whom a COA is not available in an approved, validated translation, that COA will not be administered. 
1. 
The Day 0 assessments must be performed within 24 hours prior to study treatment administration. 
2. 
The age category selected for these assessments will be based upon the age of the participant at the time of informed consent/assent. 
3. 
The EQ-5D-Y Proxy Version 1 is recommended for children 4 to 7 years of age. Data for children <4 years of age will also be collected using the EQ-5D-Y Proxy Version 1, 
but these results will be analyzed separately from the results for children 4 to 7 years of age. 
4. 
Age-appropriate versions of the PGIS will be administered to those 3 to 7 years of age, 8 to 11 years of age, and 12 years of age. Age-appropriate versions of the PGIC will 
be administered to those 8 to 11 years of age and ≥12 years of age. The CGIC will be administered to caregivers of children <8 years of age. The CGIS will be administered to 
children <3 years of age. 

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BPIC SD = Bladder Pain/Interstitial Cystitis Symptom Diary; CGIC = Caregiver Global Impression of Change; CGIS = Caregiver Global Impression of Severity; EQ-5D-5L = 
EuroQol 5 Dimensions 5 Levels; EQ-5D-Y = EuroQol 5 Dimensions for Younger Patients; ET = Early Termination; HC = hemorrhagic cystitis; ICSI = Interstitial Cystitis Symptoms 
Index; NA = not applicable; PGIC = Patient Global Impression of Change; PGIS = Patient Global Impression of Severity; PROMIS = Patient-Reported Outcomes Measurement 
Information System. 

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APPENDIX C:  BLOOD VOLUME TABLE AND SAMPLING SCHEDULE 
Study blood sampling volumes and sampling schedule by body weight are described in the tables below. 
 
Blood Volume (mL) Drawn for Study Assessments: Adult and Pediatric Participants ≥40 kg 
Study Week 
Baseline 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Total,  
First 4 Weeks 
Week 
5 
Week 
6 
Total,  
First 8 Weeks 
Week 
12 
Week 
24 
Total,  
24 weeks 
Study Day 
0 
7 
14 
21 
28 
NA 
35 
42 
NA 
84 
168 
NA 
Visit Window 
(Days) 
NA 
±2 
±3 
±2 
±3 
NA 
±3 
±3 
NA 
±28 
±28 
NA 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
3 
3 
3 
3 
3 
15 
3 
3 
21 
3 
3 
27 
Clinical 
chemistry 
7 
7 
7 
7 
7 
35 
7 
7 
49 
7 
7 
63 
Viral load 
(plasma) 
24 
24 
24 
24 
24 
120 
24 
24 
168 
24 
24 
216 
EBV viral load 
(PBMC) 
8 
8 
8 
8 
8 
40 
8 
8 
56 
8 
8 
72 
Banked PBMC 
DNA 
8 
8 
8 
8 
8 
40 
0 
8 
48 
8 
8 
64 
Totals 
50 
50 
50 
50 
50 
250 
42 
50 
342 
50 
50 
442 
DNA = deoxyribonucleic acid; EBV = Epstein-Barr virus; NA = not applicable: PBMC = peripheral blood mononuclear cell. 
 
 

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Blood Volume (mL) Drawn for Study Assessments: Pediatric Participants ≥30 kg to <40 kg 
Study Week 
Baseline 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Total,  
First 4 Weeks 
Week 
5 
Week 
6 
Total,  
First 8 Weeks 
Week 
12 
Week 
24 
Total,  
24 weeks 
Study Day 
0 
7 
14 
21 
28 
NA 
35 
42 
NA 
84 
168 
NA 
Visit Window (Days) 
NA 
±2 
±3 
±2 
±3 
NA 
±3 
±3 
NA 
±28 
±28 
NA 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
2 
2 
2 
2 
2 
10 
2 
2 
14 
2 
2 
18 
Clinical chemistry 
4 
4 
4 
4 
4 
20 
4 
4 
28 
4 
4 
36 
Viral load (plasma) 
12 
12 
12 
12 
12 
60 
12 
12 
84 
12 
12 
108 
EBV viral load (PBMC) 
8 
8 
8 
8 
8 
40 
8 
8 
56 
8 
8 
72 
Banked PBMC DNA 
8 
8 
8 
8 
8 
40 
0 
8 
48 
8 
8 
64 
Totals 
34 
34 
34 
34 
34 
170 
26 
34 
230 
34 
34 
298 
DNA = deoxyribonucleic acid; EBV = Epstein-Barr virus; NA = not applicable; PBMC = peripheral blood mononuclear cell. 
 
 

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Blood Volume (mL) Drawn for Study Assessments: Pediatric Participants ≥20 kg to <30 kg 
Study Week 
Baseline 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Total,  
First 4 Weeks 
Week 
5 
Week 
6 
Total,  
First 8 Weeks 
Week 
12 
Week 
24 
Total,  
24 weeks 
Study Day 
0 
7 
14 
21 
28 
NA 
35 
42 
NA 
84 
168 
NA 
Visit Window (Days) 
NA 
±2 
±3 
±2 
±3 
NA 
±3 
±3 
NA 
±28 
±28 
NA 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
2 
2 
2 
2 
2 
10 
2 
2 
14 
2 
2 
18 
Clinical chemistry 
4 
4 
4 
4 
4 
20 
4 
4 
28 
4 
4 
36 
Viral load (plasma) 
12 
12 
12 
12 
12 
60 
0 
12 
72 
12 
12 
96 
EBV viral load (PBMC) 
8 
0 
8 
0 
8 
24 
0 
8 
32 
8 
8 
48 
Banked PBMC DNA 
8 
8 
8 
8 
8 
40 
0 
8 
48 
8 
8 
64 
Totals 
34 
26 
34 
26 
34 
154 
6 
34 
194 
34 
34 
262 
DNA = deoxyribonucleic acid; EBV = Epstein-Barr virus; NA = not applicable; PBMC = peripheral blood mononuclear cell. 
 
 

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Blood Volume (mL) Drawn for Study Assessments: Pediatric Participants ≥10 kg to <20 kg 
Study Week 
Baseline 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Total,  
First 4 Weeks 
Week 
5 
Week 
6 
Total,  
First 8 Weeks 
Week 
12 
Week 
24 
Total,  
24 weeks 
Study Day 
0 
7 
14 
21 
28 
NA 
35 
42 
NA 
84 
168 
NA 
Visit Window (Days) 
NA 
±2 
±3 
±2 
±3 
NA 
±3 
±3 
NA 
±28 
±28 
NA 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
2 
2 
2 
2 
2 
10 
2 
2 
14 
2 
2 
18 
Clinical chemistry 
4 
4 
4 
4 
4 
20 
4 
4 
28 
4 
4 
36 
Viral load (plasma) 
8 
0 
8 
0 
8 
24 
0 
8 
32 
8 
8 
48 
EBV viral load (PBMC) 
4 
0 
0 
0 
0 
4 
0 
0 
4 
0 
4 
8 
Banked PBMC DNA 
4 
0 
4 
0 
4 
12 
0 
4 
16 
4 
4 
24 
Totals 
22 
6 
18 
6 
18 
70 
6 
18 
94 
18 
22 
134 
DNA = deoxyribonucleic acid; EBV = Epstein-Barr virus; NA = not applicable; PBMC = peripheral blood mononuclear cell. 
 
 

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Blood Volume (mL) Drawn for Study Assessments: Pediatric Participants <10 kg 
Study Week 
Baseline 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Total,  
First 4 Weeks 
Week 
5 
Week 
6 
Total,  
First 8 Weeks 
Week 
12 
Week 
24 
Total,  
24 weeks 
Study Day 
0 
7 
14 
21 
28 
NA 
35 
42 
NA 
84 
168 
NA 
Visit Window (Days) 
NA 
±2 
±3 
±2 
±3 
NA 
±3 
±3 
NA 
±28 
±28 
NA 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
2 
2 
2 
0 
2 
8 
0 
2 
10 
2 
2 
14 
Clinical chemistry 
2.5 
2.5 
2.5 
0 
2.5 
10 
0 
2.5 
12.5 
2.5 
2.5 
17.5 
Viral load (plasma) 
8 
0 
4 
0 
4 
16 
0 
8 
24 
8 
8 
40 
Banked PBMC DNA 
2 
0 
2 
0 
0 
4 
0 
2 
6 
2 
2 
10 
Totals 
14.5 
4.5 
10.5 
0 
8.5 
38 
0 
14.5 
52.5 
14.5 
14.5 
81.5 
DNA = deoxyribonucleic acid; NA = not applicable; PBMC = peripheral blood mononuclear cell. 
 

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Blood Sampling Notes: 
1. Starting with Baseline assessments, blood samples are to be sent to the central laboratory for 
analysis. In order to ensure that the volumes collected are within the guidelines for maximum 
blood volumes, the volumes collected vary by the weight of the participant. Additionally, in 
order to minimize blood volumes collected, blood samples sent to the local laboratory as part 
of standard of care should be used for eligibility purposes (ie, Screening assessments) 
whenever possible.  
2. Plasma viral load assays: 
a. The following viruses will be assayed: BK virus (BKV), adenovirus (AdV), 
cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and JC virus (JCV). 
b. Viral deoxyribonucleic acid (DNA) isolated from these samples will be stored for potential 
future sequencing/genotyping. 
c. Pediatric sample volumes are reduced relative to the full volume required in adults. As a 
consequence, repeat/confirmatory assays using these samples may not be performed in the 
event of an unanticipated assay failure in the laboratory. 
d. If the volume of plasma available in the laboratory for viral load assay is limited, the viral 
load assays will be prioritized as follows (highest priority to lowest priority): BKV, AdV, 
CMV, HHV-6, JCV. In some instances, an individualized prioritization may be required 
and will be communicated to the central laboratory by the Sponsor. 
3. Peripheral blood mononuclear cell (PBMC) Epstein-Barr virus (EBV) viral load assay: 
a. EBV viral load in blood will be assayed in PBMC and not in plasma. 
4. Banked PBMC DNA: 
a. Blood collected in cell preparation tubes will be processed to generate PBMC and plasma 
fractions. 
b. The PBMC fraction will be used to process human genetic DNA which will be 
cryopreserved for potential future evaluation of virus-specific T cell persistence by DNA 
sequencing (PBMC fraction). 
c. The plasma fraction will be cryopreserved for potential future evaluation of cytokines 
and/or other humoral markers of inflammation/immune function. 
5. For pediatric participants, blood sampling requirements for the study have been minimized by 
reducing the volume per sample collected, and by omitting collection at certain time points.  
 

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APPENDIX D:  CLINICAL LABORATORY ANALYTES 
Clinical Chemistry Panel [1] 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase  
Bicarbonate 
Blood urea nitrogen  
Calcium 
Chloride 
Creatine kinase 
Creatinine [2, 3] 
Cystatin C [3] 
Direct bilirubin  
Glucose 
Lactate dehydrogenase  
Lipase  
Potassium  
Sodium  
Total bilirubin  
Total protein  
 
1. 
Central or local laboratory results including those obtained as standard of care may be used to determine eligibility. Blood 
samples from Day 0 (pre-infusion baseline) and onward must be collected for analysis at the central laboratory. 
2. 
For determination of study eligibility: creatinine clearance using the Cockcroft-Gault equation for adult participants, eGFR 
using the Schwartz equation for pediatric participants. 
3. 
For the exploratory objective evaluating renal function over the 24-week study period, eGFR will be estimated using 
creatinine and cystatin C alone and in combination. 
eGFR = estimated glomerular filtration rate. 
Sources: Laskin BL, Denburg MR, Furth SL, et al. The natural history of BK polyomavirus and the host immune response after 
stem cell transplantation. Clin Infect Dis. 2019;pii:ciz1194. doi: 10.1093/cid/ciz1194. [Epub ahead of print] (see Reference 46); 
and Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl 
J Med. 2012 Jul 5;367(1):20-9. 
 
Hematology (Central Laboratory) 
Hematocrit 
Hemoglobin 
Platelets 
Red blood cell count 
White blood cell count and differential [1] 
 
1. 
Manual microscopic review is performed only if white blood cell count and/or differential values are out of reference range. 
 
Viral Load in Blood and Urine (Central Laboratory)  
Adenovirus  
BK virus  
Cytomegalovirus  
Epstein-Barr virus  
Human herpesvirus 6  
JC virus  
Note: When viral load determination is performed in the laboratory, residual viral DNA will be stored for potential viral 
sequencing and genotyping in the event of recurrent infection. 
Note: Viral load determination at screening may be performed at a local or central laboratory for the purpose of determining 
eligibility. Blood and urine from Day 0 (pre-infusion baseline) and onward must be collected for viral load analysis at the central 
laboratory. Additional post-infusion samples may be collected, as clinically indicated. 
DNA = deoxyribonucleic acid. 
 
 
 

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Urinalysis 
 Blood (if positive, reflex to microscopy) 
Leukocyte esterase  
 
Stool Specimen (Central Laboratory) 
Adenovirus 
Cytomegalovirus  
Note: If a stool specimen is clinically indicated, stool samples will also be sent to the central laboratory for research purposes. 
 
Cerebrospinal Fluid Sample (Central Laboratory) 
Cytomegalovirus 
Human herpesvirus 6 
JC virus 
 
Note: If a cerebrospinal fluid sample is clinically indicated, samples will also be sent to the central laboratory for research 
purposes. Cerebrospinal fluid samples required for clinical care of the participant take precedence over these research-related 
evaluations. 
 
Other Laboratory Assessments 
Serum pregnancy test [1] 
Urine pregnancy test [1] 
Follicle-stimulating hormone [2] 
Peripheral blood mononuclear cells (PBMCs) 
and plasma [3] 
1. 
For participants of childbearing potential only. A serum (human chorionic gonadotropin) pregnancy test will be performed 
at screening. A urine or serum pregnancy test must be performed <24 hours before each infusion and at the end of study 
visit for participants of childbearing potential. A negative result must be confirmed prior to administration of each infusion. 
These tests may be performed at the local laboratory.  
2. 
Follicle-stimulating hormone will be tested at screening for women of nonchildbearing potential who are postmenopausal, 
defined as 12 consecutive months with no menses without an alternative medical cause. 
3. 
At each time point indicated in Appendix A, blood will be collected into a cell separation tube and processed to generate a 
PBMC fraction and a plasma fraction. Human genetic DNA will be extracted from the PBMC fraction. The DNA from 
PBMC and plasma fractions will be cryopreserved for potential future evaluation of virus-specific T cell persistence (PBMC 
fraction) and for future evaluation of cytokines and/or other humoral markers of inflammation/immune function (plasma 
fraction). 
DNA = deoxyribonucleic acid; PBMC = peripheral blood mononuclear cell. 
 

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APPENDIX E:  GRAFT VERSUS HOST DISEASE SCALES 
MAGIC Criteria for Staging and Grading of Acute Graft Versus Host Disease 
Stage 
Skin 
(Active Erythema Only) 
Liver 
(Bilirubin) 
Upper GI 
Lower GI 
(Stool Output/Day) 
0 
No active (erythematous) 
GVHD rash 
<2 mg/dL 
No or intermittent 
nausea, vomiting, 
or anorexia 
Adult: <500 mL/day or 
<3 episodes/day. 
Child: <10 mL/kg per day or 
<4 episodes/day. 
1 
Maculopapular rash 
<25% BSA 
2-3 mg/dL 
Persistent nausea, 
vomiting, or 
anorexia 
Adult: 500-999 mL/day or 
3-4 episodes/day. 
Child: 10-19.9 mL/kg per day 
or 4-6 episodes/day. 
2 
Maculopapular rash 
25%-50% BSA 
3.1-6 mg/dL 
- 
Adult: 1000-1500 mL/day or 
5-7 episodes/day. 
Child: 20-30 mL/kg per day or 
7-10 episodes/day. 
3 
Maculopapular rash 
>50% BSA 
6.1-15 mg/dL 
- 
Adult: >1500 mL/day or 
>7 episodes/day. 
Child: >30 mL/kg per day or 
>10 episodes/day. 
4 
Generalized erythroderma 
(>50% BSA) plus bullous 
formation and desquamation 
>5% BSA 
>15 mg/dL 
- 
Severe abdominal pain with or 
without ileus or grossly bloody 
stool (regardless of stool 
volume). 
Note: Overall clinical grade (based on most severe target organ involvement): 
Grade 0: No Stage 1 to 4 of any organ. 
Grade I: Stage 1 to 2 skin without liver, upper GI, or lower GI involvement.  
Grade II: Stage 3 rash and/or Stage 1 liver and/or Stage 1 upper GI and/or Stage 1 lower GI. 
Grade III: Stage 2 to 3 liver and/or Stage 2 to 3 lower GI, with Stage 0 to 3 skin and/or Stage 0 to 1 upper GI. 
Grade IV: Stage 4 skin, liver, or lower GI involvement, with Stage 0 to 1 upper GI. 
BSA = body surface area; GI = gastrointestinal; GVHD = graft versus host disease. 
Source: Harris AC, Young R, Devine S, et al. International, multicenter standardization of acute graft-versus-host disease clinical 
data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 
2016;22(1):4-10. 
 
 

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Response Definitions for Acute Graft Versus Host Disease 
Response Term 
Definition 
CR 
Complete resolution of all signs and symptoms of GVHD in all organs without 
intervening salvage therapies. 
PR 
Improvement of 1 stage in 1 or more organs involved by GVHD without progression 
in others. 
Mixed response 
Improvement in at least 1 involved organ with progression or newly developed 
GVHD in 1 or more organs. 
Progression 
Worsening in 1 or more organs by 1 or more stage without improvement in any 
involved organ. 
NR 
No improvement or deterioration in any organ within 14 days of therapy initiation. 
CR = complete response; GVHD = graft versus host disease; NR = no response; PR = partial response. 
Source: Center for International Blood & Marrow Transplant Research (CIBMTR). Clinical trial endpoints for participants with 
acute GVHD. May 2009. 
https://www.cibmtr.org/Meetings/Materials/GVHDworkshop/GvHD%20Workshop%20Library/08_Alousi_FDAaGVHDwrkshp
_May09.pdf. Accessed 09 Nov 2020. 
 
National Institutes of Health Global Severity of Chronic Graft Versus Host Disease 
Mild Chronic GVHD 
Moderate Chronic GVHD 
Severe Chronic GVHD 
1 or 2 organs involved with no 
more than score 1 plus lung score 0 
3 or more organs involved with no 
more than score 1 or at least 
1 organ (not lung) with a score of 2 
or lung score 1 
At least 1 organ with a score of 3 or 
lung score of 2 or 3 
Note: Key points:  
In skin: higher of the 2 scores to be used for calculating global severity. 
In lung: FEV1 is used instead of clinical score for calculating global severity. 
If the entire abnormality in an organ is noted to be unequivocally explained by a non-GVHD documented cause, that organ is not 
included for calculation of the global severity. 
If the abnormality in an organ is attributed to multifactorial causes (GVHD plus other causes), the scored organ will be used for 
calculation of the global severity regardless of the contributing causes (no downgrading of organ severity score). 
GVHD = graft versus host disease. 
Source: Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development Project on Criteria for 
Clinical Trials in Chronic Graft-Versus-Host-Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood 
Marrow Transplant. 2015;21:389-401.e1. 
 
 

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National Institutes of Health Response Determinations for Chronic Graft Versus Host 
Disease 
Organ 
Complete Response 
Partial Response 
Progression 
Skin 
NIH Skin Score 0 after 
previous involvement 
Decrease in NIH Skin Score 
by 1 or more points 
Increase in NIH Skin Score by 
1 or more points, except 0 to 1 
Eyes 
NIH Eye Score 0 after 
previous involvement 
Decrease in NIH Eye Score 
by 1 or more points 
Increase in NIH Eye Score by 
1 or more points, except 0 to 1 
Mouth 
NIH Modified Oral Mucosa 
Rating Score 0 after previous 
involvement 
Decrease in NIH Modified 
Oral Mucosa Rating Score of 
2 or more points 
Increase in NIH Modified 
Oral Mucosa Rating Score of 
2 or more points 
Esophagus 
NIH Esophagus Score 0 after 
previous involvement 
Decrease in NIH Esophagus 
Score by 1 or more points 
Increase in NIH Esophagus 
Score by 1 or more points, 
except 0 to 1 
Upper GI 
NIH Upper GI Score 0 after 
previous involvement 
Decrease in NIH Upper GI 
Score by 1 or more points 
Increase in NIH Upper GI 
Score by 1 or more points, 
except 0 to 1 
Lower GI 
NIH Lower GI Score 0 after 
previous involvement 
Decrease in NIH Lower GI 
Score by 1 or more points 
Increase in NIH Lower GI 
Score by 1 or more points, 
except from 0 to 1 
Liver 
Normal ALT, alkaline 
phosphatase, and total 
bilirubin after previous 
elevation of 1 or more 
Decrease by 50% 
Increase by 2ULN 
Lungs 
Normal %FEV1 after 
previous involvement 
 
If PFTs not available, NIH 
Lung Symptom Score 0 after 
previous involvement 
Increase by 10% predicted 
absolute value of %FEV1 
 
If PFTs not available, 
decrease in NIH Lung 
Symptom Score by 1 or more 
points 
Decrease by 10% predicted 
absolute value of %FEV1 
 
If PFTs not available, increase 
in NIH Lung Symptom Score 
by 1 or more points, except 0 
to 1 
Joints and 
fascia 
Both NIH Joint and Fascia 
Score 0 and P-ROM score 25 
after previous involvement by 
at least 1 measure 
Decrease in NIH Joint and 
Fascia Score by 1 or more 
points or increase in P-ROM 
score by 1 point for any site 
Increase in NIH Joint and 
Fascia Score by 1 or more 
points or decrease in P-ROM 
score by 1 point for any site 
Global 
Clinician overall severity 
score 0 
Clinician overall severity 
score decreases by 2 or more 
points on a 0-10 scale 
Clinician overall severity 
score increases by 2 or more 
points on a 0-10 scale 
%FEV1 = percent predicted forced expiratory volume in the first second; ALT = alanine aminotransferase; GI = gastrointestinal; 
NIH = National Institutes of Health; PFT = pulmonary function test; P-ROM = photographic range of motion; ULN = upper limit 
of normal. 
Source: Lee ST, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic graft-versus-host disease. Biol Blood Marrow 
Transplant. 2015;21(6):984-999. 
 
 

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APPENDIX F:  CYTOKINE RELEASE SYNDROME SCALE 
For participants who have a presumptive diagnosis of cytokine release syndrome (CRS) based on 
the clinical judgement of the Investigator, the CRS should be graded according to the American 
Society for Transplantation and Cellular Therapy (ASTCT) consensus grading for CRS shown in 
the table below rather than by CTCAE. The ASTCT consensus grading was developed for chimeric 
antigen receptor (CAR)-T cell therapies in which sustained engagement between CAR-T cells and 
targeted malignant cells is expected, leading to substantial rates of CRS. By contrast, CRS remains 
only a theoretical concern for virus-specific T cells.  
CRS is defined as a supraphysiologic response following any immune therapy that results in the 
activation or engagement of endogenous or infused T cells and/or other immune effector cells. 
Symptoms can be progressive, must include fever at the onset, and may include hypotension, 
capillary leak (hypoxia), and end organ dysfunction. (For additional details, see Appendix G 
below.) 
Symptoms of Cytokine Release Syndrome by Grade 
Grade 
1 
2 
3 
4 
CRS Parameter 
 
 
 
 
Fever [a] 
38.0C 
38.0C 
38.0C 
38.0C 
With 
Hypotension 
None 
Not requiring 
vasopressors. 
Requiring vasopressors 
with or without 
vasopressin. 
Requiring multiple 
vasopressors (excluding 
vasopressin). 
And/or [b] 
Hypoxia 
None 
Requiring low-flow 
nasal cannula 
(oxygen delivered at 
6 L/minute) or 
blow-by. 
Requiring high-flow 
nasal cannula (oxygen 
delivered at 
>6 L/minute), facemask, 
nonrebreather mask, or 
Venturi mask. 
Requiring positive 
pressure (eg, CPAP, 
BiPAP, intubation, 
mechanical ventilation). 
Note: Organ toxicities associated with CRS may be graded according to CTCAE v5.0 but they do not influence CRS grading. 
Note: Grade 5 CRS is defined as death due to CRS in which another cause is not the principal factor leading to the outcome. 
a. Fever is defined as temperature 38.0C not attributable to any other cause. In participants who have CRS and then receive 
antipyretic or anticytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity. 
In this case, CRS grading is driven by hypotension and/or hypoxia. 
b. CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For example, a 
participant with temperature of 39.5C, hypotension requiring 1 vasopressor, and hypoxia requiring low-flow nasal cannula is 
classified as grade 3 CRS. 
BiPAP = bilevel positive airway pressure; CPAP = continuous positive airway pressure; CRS = cytokine release syndrome; CTCAE 
= Common Terminology Criteria for Adverse Events. 
Source: Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic 
toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. 

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APPENDIX G:  MONITORING FOR AND MANAGEMENT OF 
CYTOKINE RELEASE SYNDROME 
The following recommendations have been adapted from recommendations for patients receiving 
chimeric antigen receptor (CAR)-T cells who develop cytokine release syndrome (CRS).
1 CRS is 
common following CAR-T cell therapy, but remains a theoretical concern following infusion of 
virus-specific T cells (VSTs). No cases of CRS were observed in 58 participants in the phase 2 
CHARMS study of VSTs for viral infections following allogeneic hematopoietic cell transplant 
(HCT).
2 Nevertheless, Investigators should remain vigilant for the signs and symptoms of CRS, 
particularly during the first four weeks following VST infusion, and should be prepared to treat 
participants immediately for CRS should it develop. Investigators should also counsel participants 
to seek immediate medical attention if they develop concerning clinical findings. At the first sign 
of CRS, immediately evaluate the participant for hospitalization and institute treatment as outlined 
below or according to treatment protocols in use at the study site. CRS typically begins within 1 
to 14 days (median 2 to 3 days) after CAR-T cell therapy.
3 
It is also important to note that the common symptoms of CRS are not unique to CRS and clinicians 
must be cautious and exclude other causes of fever, hypotension, hemodynamic instability, and/or 
respiratory distress, such as an overwhelming infection.4 
 
 

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Treatment of Cytokine Release Syndrome 
CRS Grade 
CRS Severity 
Management 
1 
Prodromal syndrome:  
Low-grade fever, fatigue, anorexia 
Observe in person; exclude infection; administer 
antibiotics per local guidelines if neutropenic; provide 
symptomatic support. 
2 
CRS requiring mild intervention (≥1 
of the following):  
• 
High fever  
• 
Hypoxia  
• 
Mild hypotension 
Administer antipyretics, oxygen, intravenous fluids and/or 
low-dose vasopressors as needed. 
3 to 4 
CRS requiring moderate to aggressive 
intervention (≥1 of the following):  
• 
Hemodynamic instability 
despite intravenous (IV) 
fluids and vasopressor 
support  
• 
Worsening respiratory 
distress, including 
pulmonary infiltrates 
increasing oxygen 
requirement including high-
flow oxygen and/or need for 
mechanical ventilation  
• 
Rapid clinical deterioration 
Administer high-dose and/or multiple vasopressors, 
oxygen, mechanical ventilation and/or other supportive 
care as needed.  
Administer tocilizumab: 
• 
Patient weight <30 kg: 12 mg/kg IV over 1 hour  
• 
Patient weight ≥30 kg: 8 mg/kg IV over 1 hour 
(maximum dose 800 mg)  
If there is no clinical improvement, repeat tocilizumab 
after a minimum interval of 8 hours. 
If there is no response to a second dose of tocilizumab, 
consider a third dose of tocilizumab or pursue alternative 
measures for treatment of CRS. Limit to a maximum total 
of 4 doses of tocilizumab.  
If there is no clinical improvement within 12 to 18 hours 
of the first tocilizumab dose, or if there is worsening at 
any time, administer methylprednisolone 2 mg/kg IV as 
an initial dose, then 2 mg/kg IV per day until vasopressors 
and high-flow oxygen are no longer needed, then taper. 
CRS = cytokine release syndrome; IV = intravenous. 
References:  
1. KYMRIAH® 
(tisagenlecleucel) 
suspension 
for 
intravenous 
infusion, 
prescribing 
information. 
https://www.novartis.us/sites/www.novartis.us/files/kymriah.pdf. Accessed on 09 Nov 2020. 
2. Tzannou I, Papadopoulou A, Naik S, et al. Off-the-shelf virus-specific T cells to treat BK virus, human herpesvirus 
6, cytomegalovirus, Epstein-Barr virus, and adenovirus infections after allogeneic hematopoietic stem-cell 
transplantation. J Clin Oncol. 2017;35(31):3547-3557.  
3. Porter DL and Maloney DG. Cytokine release syndrome (CRS). Post TW, ed. UpToDate. Waltham, MA. Updated 
06 Apr 2020. https://www.uptodate.com/contents/cytokine-release-syndrome-crs. Accessed on 09 Nov 2020. 
4.  Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and 
neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. 

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APPENDIX H:  CONTRACEPTIVE REQUIREMENTS 
Effective methods of contraception for use in this study are: 
a. Intrauterine device. 
b. Stable dose of hormonal birth control, such as those listed below, for at least 3 months prior 
to enrollment. 
• Hormonal contraceptive tablets. 
• Injectable hormonal contraceptives. 
• Implanted hormonal contraceptives. 
• Cutaneous contraceptive patches. 
• Intravaginal hormonal contraceptive rings. 
c. At least 1 barrier method. Effective barrier methods for use in this study are: 
• Male or female condom. 
• Diaphragm. 
A female is considered to be of “childbearing potential” if she has experienced menarche and is 
not permanently sterile or postmenopausal (postmenopausal is defined as 12 consecutive months 
with no menses without an alternative medical cause and with a serum follicle-stimulating 
hormone test result in the postmenopausal range). Surgically sterile females (eg, status post-
hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) may enter the study with 
historical documentation of the surgical procedure and a negative pregnancy test at study entry. If 
a female participant has a male partner who has had surgery to prevent pregnancy (vasectomy), 
that will be considered evidence of effective contraception for the purpose of this study, provided: 
a) that the male partner is the sole sexual partner of the participant, and b) historical documentation 
of the procedure is provided. 
In addition to routine contraceptive methods, “effective contraception” also includes heterosexual 
celibacy for the entire duration of the study and for 90 days after the last dose of study treatment. 
Abstinence (celibacy) should only be used as a contraceptive method if it is in line with the 
participant’s usual and preferred lifestyle. Periodic abstinence (calendar, symptothermal, 
postovulation methods) is not an acceptable method of contraception. If at any point a previously 
celibate participant chooses to become heterosexually active during the time period for use of 
contraceptive measures specified above, he/she is responsible for initiating effective contraceptive 
measures as defined above. 

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