Conditions: Adenovirus Infection
Keywords: Allogeneic Hematopoietic Cell Transplant Adenoviremia Adenovirus Stem Cell Transplant Posoleucel ALVR105 Bone Marrow Transplant
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 57
Healthy volunteers: no

Brief summary:
This study will assess the safety and efficacy of Posoleucel for the treatment of adenovirus (AdV) infection in pediatric and adult allo-HCT recipients receiving standard of care (SoC).

Detailed description:
During the period of immune recovery after allogeneic hematopoietic cell transplant (allo-HCT), viral infections and reactivations, including those with AdV, are an important cause of morbidity and mortality. Progression to AdV disease is associated with significant morbidity and mortality rates. This Phase 3, multicenter, randomized, double-blind, placebo-controlled study will assess the safety and efficacy of Posoleucel for the treatment of AdV infection in pediatric and adult allo-HCT recipients receiving SoC.

Arms:
arm 1: Posoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria arm 2: Placebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria

Interventions: intervention 1: Posoleucel intervention 2: Placebo
Intervention descriptions: intervention 1: Administered as 2-4 milliliter infusion, visually identical to placebo intervention 2: Administered as 2-4 milliliter infusion, visually identical to Posoleucel

Protocol document:
Prot_000.pdf: 
Protocol Number: P-105-303 
 
Official Title:  
Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, with Cross-Over, of Posoleucel 
(ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving 
Standard of Care Following Allogeneic Hematopoietic Cell Transplantation 
 
NCT Number: NCT05179057 
 
Document Date: 30 November 2023 


AlloVir 
Clinical Study Protocol P-105-303 
 
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Version 5.0, 30 November 2023 
CLINICAL STUDY PROTOCOL 
 
Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, with Cross-
Over, of Posoleucel (ALVR105) for the Treatment of Adenovirus Infection in 
Pediatric and Adult Participants Receiving Standard of Care Following 
Allogeneic Hematopoietic Cell Transplantation  
 
Investigational Product: Posoleucel (ALVR105) 
Protocol Number: P-105-303 
 
IND: 27955 
EudraCT: 2021-003450-22 
 
 
Sponsor: 
AlloVir 
1100 Winter Street 
Waltham, MA 02451 
United States 
Telephone: +1-617-433-2605 
Fax: +1-339-204-9528 
 
 
Version Number: 5.0 
Original Protocol: 20 August 2021 
Amendment 1: 17 December 2021 
Amendment 2: 23 August 2022 
Amendment 3: 21 September 2023 
Amendment 4: 30 November 2023 
  
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written 
consent of 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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SIGNATURE PAGE  
STUDY TITLE:  
 
We, the undersigned, have read this protocol and agree that it contains all necessary information 
required to conduct the study. 
 
 
AlloVir 
 
 
AlloVir 
 
 
AlloVir 


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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 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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Version 5.0, 30 November 2023 
TABLE OF CONTENTS 
Signature Page ................................................................................................................................ 2 
Investigator Agreement ................................................................................................................... 3 
Table of Contents ............................................................................................................................ 4 
List of Tables .................................................................................................................................. 7 
List of Figures ................................................................................................................................. 7 
1 Synopsis .................................................................................................................................... 8 
2 Schedule of Activities ............................................................................................................. 23 
3 Introduction ............................................................................................................................. 29 
3.1 
Study Rationale ............................................................................................................. 29 
3.2 
Background ................................................................................................................... 29 
3.3 
Benefit/Risk Assessment ............................................................................................... 30 
3.3.1 Potential Benefits .............................................................................................. 30 
3.3.2 Potential Risks ................................................................................................... 30 
4 Objectives and Endpoints ....................................................................................................... 32 
5 Study Design ........................................................................................................................... 35 
5.1 
Overall Design ............................................................................................................... 35 
5.2 
Participant and Study Completion ................................................................................. 37 
5.3 
End of Study Definition ................................................................................................ 38 
5.4 
Scientific Rationale for Study Design ........................................................................... 38 
5.5 
Justification for Dose .................................................................................................... 39 
6 Study Population ..................................................................................................................... 40 
6.1 
Inclusion Criteria ........................................................................................................... 40 
6.2 
Exclusion Criteria .......................................................................................................... 40 
6.3 
Lifestyle Restrictions ..................................................................................................... 41 
6.4 
Screen Failures .............................................................................................................. 41 
7 Treatments............................................................................................................................... 42 
7.1 
Treatments Administered .............................................................................................. 42 
7.1.1 Study Drug Administration ............................................................................... 45 
7.2 
Dose Modification ......................................................................................................... 45 
7.3 
Method of Treatment Assignment ................................................................................. 45 


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7.4 
Blinding ......................................................................................................................... 45 
7.5 
Preparation/Handling/Storage/Accountability .............................................................. 46 
7.6 
Treatment Compliance .................................................................................................. 46 
7.7 
Concomitant Therapy .................................................................................................... 47 
7.7.1 Permitted Concomitant Therapy ....................................................................... 47 
7.7.2 Excluded Concomitant Therapy ........................................................................ 47 
7.8 
Treatment after the End of the Study ............................................................................ 48 
8 Discontinuation/Withdrawal Criteria ...................................................................................... 48 
8.1 
Discontinuation of Study Treatment ............................................................................. 48 
8.2 
Withdrawal from the Study ........................................................................................... 49 
8.3 
Lost to Follow Up ......................................................................................................... 49 
9 Study Assessments and Procedures ........................................................................................ 50 
9.1 
Efficacy Assessments .................................................................................................... 50 
9.1.1 Viral Load Detection Using Quantitative Polymerase Chain Reaction ............ 50 
9.1.2 Target Organ Disease ........................................................................................ 51 
9.1.3 Radiological Imaging ........................................................................................ 51 
9.1.4 EQ-5D-5L, EQ-5D-Y, and EQ-5D-Y Proxy Version 1 .................................... 52 
9.2 
Adverse Events .............................................................................................................. 52 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information ............. 52 
9.2.2 Method of Detecting AEs and SAEs ................................................................. 53 
9.2.3 Follow-up of AEs and SAEs ............................................................................. 53 
9.2.4 Regulatory Reporting Requirements ................................................................. 53 
9.2.4.1 Expedited Reporting ........................................................................... 53 
9.2.5 Pregnancy .......................................................................................................... 54 
9.2.6 Adverse Events of Special Interest .................................................................... 54 
9.2.6.1 Special Situation Reports .................................................................... 55 
9.3 
Safety Assessments ....................................................................................................... 55 
9.3.1 Clinical Laboratory Evaluations ........................................................................ 56 
9.3.2 Vital Signs ......................................................................................................... 56 
9.3.3 Electrocardiograms ............................................................................................ 56 
9.3.4 Physical Examinations ...................................................................................... 56 
9.3.5 Graft Versus Host Disease ................................................................................ 56 


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9.3.5.1 Acute Graft Versus Host Disease ....................................................... 56 
9.3.5.2 Chronic Graft Versus Host Disease .................................................... 56 
9.3.6 Cytokine Release Syndrome ............................................................................. 57 
9.3.7 Post-Infusion Monitoring .................................................................................. 57 
9.4 
Pharmacokinetics .......................................................................................................... 57 
9.5 
Pharmacodynamics ........................................................................................................ 57 
9.6 
Genetics ......................................................................................................................... 57 
9.7 
Biomarkers .................................................................................................................... 57 
9.8 
Medical Resource Utilization and Health Economics ................................................... 57 
9.9 
Other Assessments and Procedures ............................................................................... 58 
9.9.1 Informed Consent .............................................................................................. 58 
9.9.2 Demographics .................................................................................................... 58 
9.9.3 Inclusion and Exclusion Criteria ....................................................................... 58 
9.9.4 Medical History ................................................................................................. 58 
9.9.5 SARS-CoV-2 Virus Assessment ....................................................................... 58 
9.9.6 Randomization .................................................................................................. 58 
10 Statistical Considerations ........................................................................................................ 59 
10.1 Sample Size Determination ........................................................................................... 59 
10.2 Populations for Analyses ............................................................................................... 59 
10.3 Statistical Analyses ....................................................................................................... 60 
10.3.1 Efficacy Analyses .............................................................................................. 60 
10.3.1.1 Primary Efficacy Endpoint Analysis .................................................. 60 
10.3.1.2 Key Secondary Efficacy Endpoint Analysis ....................................... 61 
10.3.1.3 Other Secondary Efficacy Endpoint Analyses .................................... 61 
10.3.1.4 Cross-Over Analyses .......................................................................... 61 
10.3.2 Analysis of Safety ............................................................................................. 62 
11 References ............................................................................................................................... 64 
12 Appendices .............................................................................................................................. 65 
Appendix 1: Abbreviations ........................................................................................................... 66 
Appendix 2: Study Governance Considerations ........................................................................... 69 
Appendix 3: Clinical Laboratory Tests ......................................................................................... 75 
Appendix 4: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting .................................................................................................................... 78 


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Appendix 5: Contraceptive Guidance and Collection of Pregnancy Information ........................ 85 
Appendix 6: Graft Versus Host Disease Scales ............................................................................ 87 
Appendix 7:  Cytokine Release Syndrome Scale ......................................................................... 90 
Appendix 8:  Target Disease Endpoint Definitions ...................................................................... 91 
Appendix 9:  Estimating Fraction of Inspired Oxygen ................................................................. 95 
Appendix 10:  Amendment Changes and Rationale ..................................................................... 96 
LIST OF TABLES  
Table 1. 
Schedule of Activities for Primary Study Period ........................................................ 23 
Table 2. 
Schedule of Activities for Cross-Over Period (Participants with AdV Target Organ 
Disease by Week 10 of the Primary Study Period) ..................................................... 26 
Table 3. 
Protocol-Required Safety Laboratory Assessments .................................................... 75 
 
LIST OF FIGURES  
Figure 1. Summary of Study Design .......................................................................................... 37 
 








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• To evaluate non-relapse and all-cause 
mortality. 
 
• Non-relapse mortality1 at Week 24. 
• All-cause mortality at Week 24. 
• Death due to AdV disease. 
• To determine the percent of participants 
who have clearance of AdV in a) stool, and 
b) nasopharyngeal swab at Day 29. 
• Proportion of participants with 
undetectable AdV viral load (less than 
LLOQ) in a) stool, and b) nasopharyngeal 
swab at Day 29. 
• To assess the effect of posoleucel on time 
to resolution of AdV in stool. 
• Time to undetectable AdV viral load (less 
than LLOQ) in stool. 
• To determine the percent of participants 
with a decrease in AdV viremia of at least 
2 log10 copies/mL AdV DNA from 
randomization at Day 29. 
• Proportion of participants with a decrease 
in AdV viremia of at least 2 log10 
copies/mL AdV DNA from randomization 
at Day 29.  
• To explore the correlation between 
magnitude of AdV viremia and progression 
or non-relapse mortality1. 
• Comparison of AdV viral load versus 
progression/non-relapse mortality1. 
• To explore the correlation between 
clearance of AdV viremia and progression 
or non-relapse mortality1. 
• Comparison of the rates of 
progression/non-relapse mortality1 in those 
participants who demonstrate AdV viremia 
clearance versus those who do not. 
• To assess the age-appropriate impact on 
quality of life. 
• Change in the European Quality of Life 5 
dimensions (EQ-5D) at Day 29 and 
Week 24. 
1. Non-relapse mortality is defined as death without relapse/recurrence post allo-HCT. 
Abbreviations: AAUC = time-averaged area under the concentration-time curve; AdV = adenovirus; 
AEs = adverse events; AESIs = adverse events of special interest; allo-HCT = allogeneic hematopoietic stem cell 
transplant; BKV = BK virus; CMV = cytomegalovirus; CRS = cytokine release syndrome; EQ-5D = European 
Quality of Life 5 dimension; GVHD = graft versus host disease; HHV-6 = human herpesvirus 6; JCV = John 
Cunningham virus; LLOQ = lower limit of quantitation; qPCR = quantitative polymerase chain reaction; 
SoC = standard of care. 


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POPULATION: 
Inclusion Criteria 
Patients must meet all of the following criteria in order to be eligible for enrollment into the 
study. Screening laboratory criteria can be confirmed using local or central laboratories. 
1. Male or female of any age.   
2. Has undergone allogeneic (including umbilical cord) cell transplantation ≥21 days prior 
to dosing and has demonstrated engraftment with an absolute neutrophil count 
>500/mm3, AND has one of the following: 
a. AdV viremia DNA ≥10,000 copies/mL at screening, OR 
b. Two consecutive and rising AdV viremia DNA results of ≥1,000 copies/mL at 
screening, AND  
i. has absolute lymphocyte count <180/mm3, OR  
ii. has received T cell depletion, OR  
iii. had a cord blood transplant. 
3. Males and females of childbearing potential who engage in heterosexual intercourse must 
agree to use contraception as detailed in Appendix 5 of this protocol and refrain from 
donating sperm or eggs for at least 90 days after treatment completion. 
4. Willing and able to provide signed informed consent. 
5. Has an HLA type matching with at least 1 suitably matched and available posoleucel 
VST line for infusion.  
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from participation in the study: 
1. Grade 3 or higher acute GVHD (see Appendix 6 for information on acute GVHD grading 
and severity). 
2. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose 
>0.5 mg/kg/day or equivalent).  Patients actively undergoing corticosteroid tapering 
during Screening may randomize and dose once they have reached ≤ 1.0 mg/kg/day with 
Medical Monitor approval, with the expectation that the corticosteroid taper will 
continue. 
3. Has either of the following laboratory parameters at screening: 
a. Aspartate aminotransferase and alanine aminotransferase serum levels ≥5 times 
the upper limit of normal (ULN), OR 
b. Direct bilirubin serum levels ≥3 times the ULN. 
Exception: Patients with elevations of these laboratory parameters may be included if 
these elevations are attributed to AdV hepatitis and are not considered attributable to 
other etiologies. 


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4. Relapse of primary malignancy, or any other active malignancy, except for 
non-melanoma skin cancer. Malignancies that are slow growing and/or stable may be 
allowed with Medical Monitor approval.  
 
5. Grade 4 diarrhea (ie, life-threatening consequences with urgent intervention indicated) 
regardless of attribution ongoing or within 7 days prior to randomization. 
6. Uncontrolled viral (other than AdV), bacterial, or fungal infection(s) leading to 
hemodynamic instability or radiologic or laboratory evidence attributable to worsening 
disease. 
7. Requirement for fraction of inspired oxygen (FiO2) >0.5 (ie, 50%) to maintain arterial 
oxygen saturation >90% (via pulse oximetry) or need for mechanical ventilation, except 
for planned procedures or surgeries with Medical Monitor approval. For guidance on 
estimating fraction of inspired oxygen, see Appendix 9.  
 
8. Prior therapy with anti-thymocyte globulin, alemtuzumab (Campath®), or other 
immunosuppressive T cell monoclonal antibodies within 28 days prior to dosing. 
9. Prior donor lymphocyte infusion or CD34+ stem cell infusion within 21 days prior to 
dosing. 
10. Use of vasopressors within 7 days prior to randomization. 
11. Use of any investigational antiviral agent, including brincidofovir, within 7 days prior to 
randomization. Maribavir and letermovir for CMV will be allowed. 
12. Pregnant or lactating female unwilling to discontinue nursing prior to randomization. 
13. Any condition that, in the opinion of the Investigator, would compromise the safety of 
the patient, would prevent full participation in this study, or would interfere with the 
evaluation of any study endpoints. 
14. History of severe (Common Terminology Criteria for Adverse Events [CTCAE] Grade 
≥3) allergy to any component of posoleucel (including human serum albumin and 
dimethyl sulfoxide) or history of severe (CTCAE Grade ≥3) prior reactions to blood 
product transfusions. 
15. Positive for SARS-CoV-2 virus at screening.  
Exception: Patients who test positive for SARS-CoV-2 at screening and who have a 
recent prior positive test may be enrolled if they have no clinical or radiological 
manifestations of COVID-19 and if the Investigator and Medical Monitor concur on their 
enrollment. 
STUDY DESIGN AND DURATION:  
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the 
safety and efficacy of posoleucel as compared to placebo for the treatment of AdV infection in 
pediatric and adult recipients of HCT with AdV infections receiving SoC.  
Approximately 82 eligible patients may be randomized 
 to receive  sequential infusions of 
posoleucel or placebo (separated by 
). Randomization will be stratified 
 


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The presence or absence of adenovirus target organ disease at screening will be determined 
initially by the Investigator (using the criteria in Appendix 8) and reviewed subsequently by the 
Adjudication Committee for analysis purposes.  
The Primary Study Period is 4 weeks (28 days) for evaluation of efficacy, including the primary 
endpoint, plus 20 weeks for safety follow-up, for a total study duration of 24 weeks. For 
participants who cross-over, the Cross-Over Period is 4 weeks (28 days), plus 20 weeks for 
safety follow-up. Participants who experience recurrence and receive an additional dose will 
have safety follow-up for 20 weeks after the final dose.  
At Day 29, all participants will be assessed for the primary endpoint, virologic response.  
Option for Cross-Over 
Participants who progress to active target organ disease or whose existing target organ disease 
progresses (assessed by the Investigator and Sponsor Medical Monitor and based on the criteria 
in Appendix 8) between Day 29 and Week 10 will be considered to have experienced 
progression and will have the option to be crossed over to the alternate treatment arm. 
Participants can cross over before Day 29 only if they progress with target organ disease as 
adjudicated by the Adjudication Committee. For potential cases of premature cross-over (ie, 
prior to Day 29), participants will be expected to have received both infusions of study treatment 
before evaluation by the Adjudication Committee. Cross-over participants will receive the 
alternate treatment to which they were originally randomized, posoleucel or placebo 
 infusions separated by 
), but study treatment will remain blinded. 
Participants must meet the following eligibility criteria to cross-over: participant must not have 
evidence of acute GVHD Grade 3 or higher (Exclusion Criterion 1), must not be receiving 
ongoing therapy with high-dose systemic corticosteroids >0.5 mg/kg/day prednisone or 
equivalent unless approved by Medical Monitor (Exclusion Criterion 2), and must not have 
experienced a severe infusion-related reaction (Grade ≥3) with the prior doses of study treatment 
(posoleucel or placebo).  
If the participant receives any antiviral drugs in violation of the protocol during the study, that 
participant will be included in the primary analysis, but will not be eligible for cross-over. 
Follow-up will be continued for safety and persistence of the virus specific T cells (VSTs). 
Participants must meet all of the cross-over eligibility criteria by Week 10 of the Primary Study 
Period to enter the Cross-Over Period. A new baseline (Day 1’ of the Cross-Over Period) will be 
established at the time of the first cross-over infusion. At Day 29’ of the Cross-Over Period, 
participants will be assessed for clinical and virologic response. The participants will then have 
20 weeks of safety follow-up, for a total duration of 24 weeks for the Cross-Over Period. The 
maximum study duration for participants who cross over is 34 weeks, including up to 10 weeks 
in the Primary Study Period and 24 weeks in the Cross-Over Period.  
Participants who cross over are not eligible to receive treatment for recurrence (described 
below). 




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Oversight Committees 
An independent Data and Safety Monitoring Board (DSMB) will be convened for this study to 
routinely monitor participant safety and evaluate prespecified interim analyses for futility and 
sample size re-estimation (SSRE).  
An independent and blinded Adjudication Committee will adjudicate progression from AdV 
viremia to target organ disease and progression of AdV target organ disease during the study.  
Assessment Overview 
Viral load of AdV will be measured at the central laboratory at each visit from blood and stool 
samples and at Day -21 to -1 and Day 29 from nasopharyngeal swab. Blood specimens collected 
should be analyzed by the central laboratory for screening purposes, however, local laboratory 
results available up to 5 days prior to and/or during screening will be acceptable to determine 
eligibility. For the inclusion criterion requiring two consecutive and rising AdV viremia results 
exceeding 1,000 copies/mL, the two consecutive viremia results used to determine eligibility 
must have been assayed at the same laboratory, preferably the central laboratory however, local 
lab results are also acceptable (with Medical Monitor approval). This process is expected to 
expedite the randomization and dosing of participants whose clinical status may rapidly 
deteriorate. A central laboratory blood sample must be collected prior to dosing on Day 1. All 
study analyses will continue to be performed using viral load data from the central laboratory.   
Participants will be followed weekly for viremia and viral load in the stool while symptomatic. 
For participants who require intubation and/or undergo bronchoscopy with bronchoalveolar 
lavage (BAL), a sample of BAL fluid should, when possible, be obtained for AdV viral load 
determination at the central laboratory. For participants who develop symptoms and/or signs of 
possible AdV-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 AdV viral load determination should, when possible, be 
sent to the central laboratory. In all cases, BAL and CSF samples required for routine clinical 
care of the patient take precedence over these study-related evaluations.  
The presence or absence of abnormalities consistent with lower respiratory tract infection on 
chest X-ray and/or CT scan as assessed by the local radiologist should be documented at 
screening (obtained no more than 10 days prior to dosing) and at Day 29 (±3 days). If no routine 
clinical radiological imaging of the chest is available at either of these timepoints, a chest X-ray  
should be obtained (chest CT scan is not a study-mandated procedure; however, the results of 
chest CT scan[s] performed as part of a participant’s standard clinical care may be used for the 
purposes of the study). For those participants who cross over, chest imaging as described above 
should be documented within 7 days prior to Day 1’ of the Cross-Over Period and at Day 29’ 
(±3 days) of the Cross-Over Period. If the Day 29 imaging from the Primary Study Period falls 
within the 7-day window prior to cross over, this imaging need not be repeated prior to the 
participant entering the Cross-Over Period (ie, the Day 29 imaging will serve as the baseline 
imaging for the Cross-Over Period). All chest X-rays and/or CT scans will also be submitted for 
central reading, which will be used for analysis purposes. 
For evaluation of potential renal, urinary tract, and pancreatic manifestations of AdV infection, a 
urinalysis (dipstick and microscopy) will be obtained at the local laboratory at Day 1 and Day 


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29, and serum amylase and lipase levels will be included in the clinical chemistry evaluations at 
the central laboratory. 
Blood samples will be obtained from all participants for the measurement of posoleucel cell 
persistence through Week 24. 
Repeat or unscheduled samples may be taken based on symptoms, for safety reasons, or for 
technical issues with the samples. 
Safety assessments will include adverse event (AE) monitoring, clinical laboratory assessments, 
physical examinations, vital sign measurements, and 12-lead electrocardiograms (ECGs). 
Additional safety assessments may be performed throughout the duration of the study if 
clinically indicated. 
AEs of special interest (AESIs) include the following: 
• Acute or chronic GVHD 
• CRS 
• Infusion-related reactions (IRRs) 
• Graft failure and rejection 
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
Posoleucel will be frozen in a cryopreservation medium containing
 
 
 
Posoleucel will be supplied in 
 cryovials at a concentration of 
 
 
 
Placebo is a 
. Upon thaw, 
under normal light conditions without magnification, both posoleucel and placebo are clear 
straw-colored liquids.   
Posoleucel is to be administered at a fixed cell dose based on weight, as 
sequential infusions 
separated by 
 
Dose #  
(Study Day) 
Criteria 
Dose 1  
(Study Day 1/ 
Study Day 1’) 
Dose levels for all infusions will be as follows: 
• 
 
 
 
• 
 
 
 


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Dose 2 
(Study 
 
 
All participants will receive a 2nd dose based on response after the 1st dose: 
• If AdV viral load decrease from baseline is ≥0.5 log10 copies/mL 
AdV DNA at Days 8 or 11/Days 8’ or 11’, the participant will 
receive a second dose with the same VST line or placebo lot as the 
first dose, 
• If AdV viral load decrease from baseline is <0.5 log10 copies/mL 
AdV DNA at Days 8 or 11/Days 8’ or 11’, the participant will 
receive a second dose with a new VST line from a different donor or 
placebo from a different lot.  
For participants who receive an additional dose for recurrence, the additional dose will be from 
the same VST line or placebo lot and include the same number of cells as the second dose. An 
additional dose for recurrence can only be administered after Day 29 of the Primary Study 
Period (the primary endpoint), but prior to 20 weeks. Participants who receive an additional dose 
for recurrence are not eligible for subsequent cross-over, and participants who have previously 
entered the Cross-Over Period are not eligible for a subsequent additional dose. 
Participants who have experienced new onset of GVHD, worsening of GVHD, or a Grade ≥3 
IRR will be excluded from redosing with additional doses of blinded study treatment. Reference 
Section 8.1 for Discontinuation of Study Treatment for details.  
STATISTICAL ANALYSES: 
In order to control the overall type 1 error rate, a sequential approach will be used to analyze the 
primary and key secondary efficacy endpoints, with undetectable viremia (less than LLOQ) at 
Day 29 of the Primary Study Period as the primary efficacy endpoint, followed by progression 
from viremia to target organ disease (for participants without target organ disease at screening), 
progression of target organ disease (for participants with target organ disease at screening), or 
non-relapse mortality during the study as the key secondary efficacy endpoint. 
Summary statistics will be presented by treatment group for the Primary Study Period and by 
cross-over group (Posoleucel/Placebo or Placebo/Posoleucel) based on the treatments received 
for the Cross-Over Period. 
Analysis Populations 
Intent-to-Treat (ITT) Population 
The ITT Population will include all randomized participants. Participants will be analyzed 
according to the randomized study treatment.  
Modified Intent-to-Treat (mITT) Population 
The mITT Population will include all randomized participants who receive at least one dose of 
posoleucel or placebo. All efficacy endpoints will be analyzed based on the mITT Population, 
and these analyses will be considered the primary analyses of efficacy. Participants will be 
analyzed according to the randomized study treatment.  


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Per Protocol Population 
The Per Protocol (PP) Population will include all ITT participants who receive any amount of 
posoleucel or placebo and who do not have any major protocol deviations deemed potentially to 
impact efficacy or its evaluation, as defined in the statistical analysis plan (SAP). All efficacy 
endpoints will also be analyzed based on the PP Population, and these analyses will be 
considered secondary analyses of efficacy. Participants will be analyzed according to the 
randomized study treatment. 
Safety Population 
The Safety Population will include all participants who receive any amount of posoleucel or 
placebo and have at least 1 post-treatment safety assessment. All safety analyses will be based 
on the Safety Population, and participants will be analyzed according to the actual study 
treatment received. 
Efficacy 
All efficacy endpoints will be analyzed and formally compared between randomized treatment 
groups using statistical tests based on data from the Primary Study Period. In addition, for 
purposes of complete reporting, results for these endpoints will be reported, if appropriate, for 
data from the Cross-Over Period by treatment received in the Cross-Over Period, but no formal 
comparisons or statistical tests will be made. 
Primary Efficacy Endpoint Analysis 
The primary efficacy endpoint, undetectable viremia (less than LLOQ) at Day 29 of the Primary 
Study Period, will be summarized by treatment group using the count and percentage, together 
with an exact (Clopper-Pearson) 95% confidence interval for the true percentage.  
The null hypothesis is that the true percentage for posoleucel plus SoC is less than or equal to the 
true percentage for placebo plus SoC, and the alternative hypothesis is that it is greater. This 
endpoint will be analyzed using logistic regression. The model will include a term for treatment 
and the following covariates: level of viremia at Baseline (≥10,000 copies/mL or <10,000 
copies/mL AdV DNA), age (≥12 years or <12 years), and absolute lymphocyte count at 
Baseline. The null hypothesis will be tested using a one-sided test of the effect of treatment at 
the 0.025 significance level.  
Key Secondary Efficacy Endpoint Analysis 
The key secondary efficacy endpoint will be tested sequentially after the primary endpoint 
reaches statistical significance. The key secondary efficacy endpoint, progression from viremia 
to target organ disease (for participants without target organ disease at screening), progression of 
target organ disease (for participants with target organ disease at screening), or non-relapse 
mortality during the study, will be analyzed in the same manner as the primary efficacy 
endpoint.  
For AdV viral endpoints at Day 29 or Week 4 visit, a 14-day window will be applied to the Day 
29 visit. The last observed plasma AdV DNA result through Day 29 + 14 days (up to 43 days 
post first infusion) will be used for the analysis. Participants who cross over on or before Day 29 
will be treated as failure. 
 


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Other Secondary Efficacy Endpoint Analyses  
Following the key secondary analysis, progression from viremia to target organ disease and 
progression of target organ disease will be analyzed as separate subgroups in a step-down 
manner. If any participants cross over prior to Day 29, they will be considered as having had 
progression, because the necessary condition for cross-over is that the participant progressed to 
active target organ disease (for participants without target organ disease at screening) or 
experienced progression of target organ disease (for participants with target organ disease at 
screening). 
The AAUC for plasma AdV viremia (log10 copies/mL AdV DNA), as assayed by qPCR, through 
Day 29 of the Primary Study Period will be summarized by treatment group using descriptive 
statistics (number of non-missing observations, mean, median, standard deviation, minimum, 
and maximum). The null hypothesis for this endpoint is that the true mean for posoleucel is 
greater than or equal to the true mean for placebo, and the alternative hypothesis is that it is less. 
The null hypothesis will be tested using a one-sided, two-sample t-test with a 0.025 significance 
level.  
The following secondary efficacy endpoints will each be analyzed in the same manner as the 
primary efficacy endpoint: achieving AdV viremia <400 copies/mL AdV DNA at Day 29 of the 
Primary Study Period and AdV disease recurrence during the study among participants who had 
clearance of AdV viremia (prior to any cross-over).  
If there are any cross-over participants who, prior to cross-over, had clearance of AdV viremia, 
these participants will be considered failures (ie, had recurrence) for the AdV disease recurrence 
during the study endpoint. 
The Kaplan-Meier estimated median time to resolution of AdV viremia will be presented for 
each treatment group, together with the 95% confidence interval for the true median. The 
number and percentage of censored and uncensored participants will be presented by treatment 
group. The null hypothesis for this endpoint is that the true distributions of time to resolution of 
AdV viremia are equal for posoleucel and placebo, and the alternative hypothesis is that the true 
distributions are different, with the time to resolution of AdV viremia being less for posoleucel. 
The null hypothesis will be tested using a one-sided log-rank test with a 0.025 significance level. 
Cross-Over Analyses 
Undetectable viremia (less than LLOQ) at Day 29’ of the Cross-Over Period will be summarized 
by cross-over group using counts and percentages, together with exact (Clopper-Pearson) 95% 
confidence intervals for the true percentages. Achieving AdV viremia <400 copies/mL AdV 
DNA at Day 29’ of the Cross-Over Period and AdV disease recurrence during the 24-week 
Cross-Over Period among participants who had clearance of AdV viremia (after cross-over) will 
be analyzed in the same way.  
The AAUC for plasma AdV viremia (log10 copies/mL AdV DNA), as assayed by qPCR, through 
Week 24’ of the Cross-Over Period will be summarized by cross-over group using descriptive 
statistics. 
The Kaplan-Meier estimated median time to resolution of AdV viremia will be presented for 
each cross-over group, together with the 95% confidence interval for the true median. Cross-
over participants who do not achieve resolution of AdV viremia will be censored as of their last 


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study visit. The number and percentage of censored and uncensored participants will be 
presented by cross-over group. 
Progression from viremia to target organ disease (for participants without target organ disease at 
screening, progression of target organ disease (for participants with target organ disease at 
screening), or non-relapse mortality during the 24-week Cross-Over Period will not be analyzed, 
because all cross-over participants must have already progressed to target organ disease prior to 
being crossed over.  
Analysis of Safety 
Safety will be analyzed and compared between treatment received based on data from the 
Primary Study Period. In addition, for purposes of complete reporting, safety will be reported for 
data from the Cross-Over Period by treatment received in the Cross-Over Period, but no 
comparisons will be made between the two treatments. 
The primary safety endpoint is the incidence and severity of TEAEs, including individual 
AESIs, during the study. The safety profile will be further assessed based on changes in clinical 
laboratory assessments, vital signs, ECGs, and physical examinations. All safety analyses will be 
based on the Safety Population. 
Safety analyses in general will be descriptive and will be presented by study period (Primary 
Study Period or Cross-Over Period) and treatment group or cross-over group in a tabular format. 
Categorical endpoints will be summarized using number and percentage of participants within 
each category. Continuous endpoints will be summarized descriptively with summary statistics 
(number of non-missing observations, mean, standard deviation, median, minimum, and 
maximum). 
The number and percentage of participants with TEAEs will be tabulated by Medical Dictionary 
for Regulatory Activities (MedDRA) System Organ Class and Preferred Term for each treatment 
group/cross-over group. This will be done overall, by severity, and by relationship to treatment. 
Adverse events leading to discontinuation of the study, SAEs, and AESIs will be summarized by 
treatment group. 
The incidence and severity of acute GVHD during the study, the incidence and severity of 
chronic GVHD during the study, the incidence and severity of CRS during the study, and the 
incidence and severity of any AESIs during the study will each be summarized by treatment 
group for the Primary Study Period and by cross-over group for the Cross-Over Period using 
counts and percentages. 


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SAMPLE SIZE DETERMINATION:  
The required sample size is 82 participants based on the below specifications that have received 
at least 1 dose of posoleucel or PBO.  
The sample size was determined based on the following specifications: 
1. Superiority study comparing posoleucel plus SoC to placebo plus SoC 
2. Primary endpoint is success or failure based on clearance of ADV viremia at Day 29 visit 
of the Primary Study Period 
3. Allocation (posoleucel:placebo) is 1:1 
4. Chi-square test  
5. Two-sided alpha = 0.05 
6. True success rate (defined as clearance of virus) for posoleucel = 0.55 
7. True success rate (defined as clearance of virus) for placebo = 0.25 
8. Power = 80% 
A SSRE and futility analysis will be performed after approximately 40 participants have 
completed Day 29 of the Primary Study Period. Details of the SSRE and futility analysis will be 
provided in the SSRE Plan prior to conducting the interim analyses.  
SITES: Approximately 50 clinical sites in the United States, Canada, and Europe. 
SPONSOR: 
AlloVir 
1100 Winter Street 
Waltham, MA 02451 
United States 
Telephone: +1-617-433-2605 
Facsimile: +1-339-204-9528 
 


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Version 5.0, 30 November 2023 
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SCHEDULE OF ACTIVITIES  
Table 1. Schedule of Activities for Primary Study Period  
Study Week (Primary Study Period) 
 
 
 
 
 
 
 
 
 
 
 
Study Day (Primary Study Period) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±3 
±3 
±3 
±5 
±5 
±28 
±28 
±42 
NA 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
I/E criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics and medical 
history [2] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HLA match for cell line selection 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SARS-CoV-2 PCR virus 
assessment (nasal/ 
nasopharyngeal swab) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
FSH test [3] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test [4] 
X 
X 
 
 
X 
 
 
 
 
X 
X 
X 
X 
Study treatment administration 
[5] 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Infusion site evaluation [6] 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Post-infusion monitoring [7] 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
COA (EQ-5D) [8] 
 
X 
 
 
 
 
X 
 
 
X 
 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hospital information [9] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination [10, 11] 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
X 
X 
Height and weight [12] 
X 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Vital signs including SpO2 [11, 
13] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG [14] 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
Chest X-ray and/or CT scan [15] 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Urinalysis [16] 
X 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
Hematology and clinical 
chemistry [16] 
X 
X 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
Coagulation (PT, INR, and PTT) 
 
X 
 
 
 
 
X 
 
 
 
 
 
 


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Study Week (Primary Study Period) 
 
 
 
 
 
 
 
 
 
 
 
Study Day (Primary Study Period) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±3 
±3 
±3 
±5 
±5 
±28 
±28 
±42 
NA 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
[16] 
Adenovirus viral load in blood 
and stool with viral DNA 
extraction and storage [16, 17] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adenovirus viral load in urine 
[16, 18] 
 
X 
BKV, CMV, JCV, EBV, and 
HHV-6 viral load in blood [16, 
19] 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Adenovirus viral load in 
nasopharyngeal swab 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Adenovirus viral load in BAL 
fluid and/or CSF [16, 20] 
 
X 
Bank PBMCs for VST 
persistence and plasma for 
cytokine evaluation [16, 21] 
 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Acute GVHD evaluation [22] 
X 
X 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
Chronic GVHD evaluation [22] 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Note: Participants may return to the clinical site more frequently as determined by their clinical condition at the discretion of the Investigator and in collaboration with the Medical 
Monitor. 
1. 
An Early Termination Visit should be performed for any participant who discontinues the study early. 
2. 
Medical history will include diagnosis of underlying disease requiring HCT, underlying disease state at the time of AdV diagnosis, type of donor and cell source of the 
transplant received, date of HCT, conditioning regimen, CMV serostatus, presence of GVHD, pulmonary function tests, and smoking status. 
3. 
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. 
4. 
A serum pregnancy test will be performed at screening for females of childbearing potential. A serum or urine pregnancy test will be repeated prior to dosing on Day 1 for 
females of childbearing potential, only if the pregnancy test performed at screening was not completed within 48 hours prior to study treatment administration. A serum or 
urine pregnancy test will be performed within 48 hours prior to each additional study treatment administration (if applicable) and at the Week 10, Week 16, Week 24, and ET 
visits for females of childbearing potential. A negative pregnancy test result is required prior to dosing. 
5. 
Participants randomized to the posoleucel group will receive posoleucel cells as an infusion. Participants randomized to the placebo group will receive an IV infusion of 
 All infusions will be administered IV over approximately 
 as a slow push. Participants will receive a second dose of blinded 
study treatment approximately 
 following the first dose.  
6. 
Includes pain, tenderness, erythema, swelling, and induration. On infusion days, performed pre-dose and at 1 hour post-dose. 
7. 
Participants will be monitored closely and must remain in the clinic for 1 hour after the end of each infusion. Vital signs will be measured at the end of the infusion, and at 
15, 30, 45, and 60 minutes after the end of the infusion. Participants must also remain on continuous pulse oximetry for 30 minutes after the end of the infusion. Post-
infusion monitoring should be completed for all infusions of study treatment. 
8. 
EQ-5D may be performed up to 24 hours prior to study treatment administration. 


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9. 
Includes information on hospital admission and discharge, ICU transfer, oxygen supplementation, and ventilation. 
10. A complete physical examination will be performed at screening. Abbreviated physical examinations will be performed at all subsequent visits. 
11. On days when study treatment is administered, perform vital signs and physical examination before study treatment administration. 
12. Height should be collected at screening only. Weight at screening should be used for all doses. 
13. Vital signs include body temperature, heart rate, respiratory rate, SpO2, and systolic and diastolic blood pressure. Vital signs will be collected after the participant has rested 
for at least 5 minutes in the supine position. 
14. Performed within 1 hour after study treatment administration on 
 
15. All participants will have screening imaging performed within 10 days prior to dosing and analyzed locally as long as the imaging can be transmitted to the central reader. 
Images (chest X-ray and/or CT scan) obtained as part of a participant’s standard clinical care may be used for the purposes of the study. If standard clinical imaging is not 
performed at these time-points, a chest X-ray should be performed for the purposes of the study.   
16. Sample must be obtained prior to infusion of study treatment. 
17. Diagnosis of AdV by blood and stool samples will be determined by the central laboratory. Samples will be stored for potential future genotypic or viral load analysis. Blood 
specimens collected locally within 5 days of screening will be acceptable to initiate screening activities; a central laboratory blood sample result should be available prior to 
dosing. Participants may be randomized and dosed (with Medical Monitor approval) based on local laboratory AdV viremia results if the central laboratory result(s) is not 
available at the time of intended dosing. Participants will be followed weekly for viremia and viral load in the stool while symptomatic. The screening, Day 1, and Day 29 
collections of stool for AdV viral load should be collected in all participants, irrespective of GI symptoms. For all other timepoints, these samples are required to be collected 
if the patient has symptoms (eg, diarrhea). If the patient does not have symptoms at these visits, stool viral load should be collected if feasible. 
18. While not a routine evaluation in this study, any participants who manifest clinical signs and/or symptoms of AdV hemorrhagic cystitis should have a urine sample sent to the 
central laboratory for determination of AdV urine viral load. For this subset of participants, AdV urine viral loads should be measured weekly at the central laboratory until 
resolution of hemorrhagic cystitis. 
19. Blood for BKV, CMV, JCV, EBV, and HHV-6 viral load should be collected prior to study treatment administration. 
20. For participants who require intubation and/or undergo bronchoscopy with BAL, a sample of BAL fluid should, when possible, be obtained for AdV viral load determination 
at the central laboratory. For participants who develop symptoms and/or signs of possible AdV-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 AdV viral load determination should, when possible, be sent to 
the central laboratory. 
21. At each time point indicated, blood will be collected into a cell separation tube and processed to generate a PBMC fraction and a plasma fraction. Genomic DNA will be 
extracted from the PBMC fraction. The genomic DNA from PBMC will be cryopreserved for potential future evaluation of VST persistence. The plasma fraction will be 
cryopreserved for potential future evaluation of cytokines and/or other humoral markers of inflammation/immune function. On Day 1 and Day 15, the sample should be 
collected pre-dose.  
22. If any participant develops GVHD, that participant 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. 
Abbreviations: AdV = adenovirus; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BAL = bronchoalveolar lavage; CBC = complete blood count; 
CIBMTR = Center for International Blood and Marrow Transplant Research; CMV = cytomegalovirus; COA = clinical outcome assessment; COVID-19 = coronavirus disease 
2019; CSF = cerebrospinal fluid; CT = computed tomography; DNA = deoxyribonucleic acid; ECG = electrocardiogram; EQ-5D = European Quality of Life 5 dimension; 
ET = Early Termination; FSH = follicle-stimulating hormone; GVHD = graft versus host disease; HCT = hematopoietic cell transplant; HLA = human leukocyte antigen; 
ICU = intensive care unit; I/E = inclusion and exclusion; IV = intravenous(ly); LFT = liver function test; MAGIC = Mount Sinai Acute GVHD International Consortium; NA = not 
applicable; PBMC = peripheral blood mononuclear cell; qPCR = quantitative polymerase chain reaction; SpO2 = peripheral capillary oxygen saturation; VST = virus-specific T 
cell. 
 
 


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Version 5.0, 30 November 2023 
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Table 2. Schedule of Activities for Cross-Over Period (Participants with AdV Target Organ Disease by Week 10 of the 
Primary Study Period)  
Study Week (Cross-Over 
Period) 
 
 
 
 
 
 
 
 
 
 
 
 
Study Day (Cross-Over Period) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±3 
±3 
±3 
±5 
±5 
±28 
±28 
±42 
NA 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cross-over I/E criteria [3] 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy test [4] 
X 
X 
 
 
X 
 
 
 
 
X 
X 
X 
X 
Study treatment 
administration [5] 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Infusion site evaluation [6] 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Post-infusion monitoring 
[7] 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
COA (EQ-5D) [8] 
 
X 
 
 
 
 
X 
 
 
X 
 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hospital information [9] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination [10, 
11] 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
X 
X 
Weight [12] 
X 
X 
 
 
 
 
 
 
 
 
 
X 
X 
Vital signs including SpO2 
[11, 13] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
12-lead ECG [14] 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
Chest X-ray and/or CT 
scan [15] 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Urinalysis [16] 
X 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
Hematology and clinical 
chemistry [16] 
X 
X 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
Coagulation (PT, INR, and 
PTT) [16] 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
Adenovirus viral load in 
blood and stool with viral 
DNA extraction and 
storage [16, 17] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Version 5.0, 30 November 2023 
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Study Week (Cross-Over 
Period) 
 
 
 
 
 
 
 
 
 
 
 
 
Study Day (Cross-Over Period) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±3 
±3 
±3 
±5 
±5 
±28 
±28 
±42 
NA 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adenovirus viral load in 
urine [16, 18] 
 
X 
BKV, CMV, JCV, EBV, 
and HHV-6 viral load in 
blood [16, 19] 
X 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Adenovirus viral load in 
nasopharyngeal swab [16] 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
Adenovirus viral load in 
BAL fluid and/or CSF [16, 
20] 
 
X 
Bank PBMCs for VST 
persistence and plasma for 
cytokine evaluation [16, 21] 
 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
Acute GVHD evaluation 
[22] 
X 
X 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
Chronic GVHD evaluation 
[22] 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
Note: Participants may return to the clinical site more frequently as determined by their clinical condition at the discretion of the Investigator and in collaboration with the Medical 
Monitor. 
1. 
If any of these evaluations have been completed within 10 days as part of the Primary Study Period, they do not have to be repeated. 
2. 
An Early Termination Visit should be performed for any participant who discontinues the study early. 
3. 
Participant must not have evidence of acute GVHD grade 3 or higher (Exclusion Criterion 1), must not be receiving ongoing therapy with high-dose systemic corticosteroids 
>0.5 mg/kg/day or equivalent unless approved by Medical Monitor (Exclusion Criterion 2), and must not have experienced a severe infusion-related reaction (Grade ≥3) with 
the prior doses of study treatment (posoleucel or placebo). 
4. 
A serum pregnancy test will be performed at cross-over for females of childbearing potential. A serum or urine pregnancy test will be repeated prior to dosing on Day 1’ for 
females of childbearing potential, only if the pregnancy test performed at cross-over was not completed within 48 hours prior to study treatment administration. A serum or 
urine pregnancy test will be performed within 48 hours prior to each additional study treatment administration (if applicable) and at the Week 10’, Week 16’, Week 24’, and 
ET visits for females of childbearing potential. A negative pregnancy test result is required prior to dosing. 
5. 
Participants who cross over to the posoleucel group will receive posoleucel cells as an infusion. Participants who cross over to the placebo group will receive an IV infusion 
of 
 All infusions will be administered IV over approximately 
as a slow push. Participants will receive a second dose of 
blinded study treatment approximately 
following the first dose.  
6. 
Includes pain, tenderness, erythema, swelling, and induration. On infusion days, performed predose and at 1 hour postdose. 
7. 
Participants will be monitored closely and must remain in the clinic for 1 hour after the end of each infusion. Vital signs will be measured at the end of the infusion, and at 
15, 30, 45, and 60 minutes after the end of the infusion. Participants must also remain on continuous pulse oximetry for 30 minutes after the end of the infusion. Post-
infusion monitoring should be completed for all infusions of study treatment. 


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Version 5.0, 30 November 2023 
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8. 
EQ-5D may be performed up to 24 hours prior to study treatment administration. 
9. 
Includes information on hospital admission and discharge, ICU transfer, oxygen supplementation, and ventilation. 
10. A complete physical examination will be performed at cross-over unless one has been completed within the past 3 days. Abbreviated physical examinations will be performed 
at all subsequent visits. 
11. On days when study treatment is administered, perform vital signs and physical examination before study treatment administration. 
12. Weight at cross-over should be used for all doses. 
13. Vital signs include body temperature, heart rate, respiratory rate, SpO2, and systolic and diastolic blood pressure. Vital signs will be collected after the participant has rested 
for at least 5 minutes in the supine position. 
14. Performed within 1 hour after study treatment administration on 
 
15. All participants will have imaging performed and analyzed locally as long as the imaging can be transmitted to the central reader. Images (chest X-ray and/or CT scan) 
obtained as part of a participant’s standard clinical care may be used for the purposes of the study. If standard clinical imaging is not performed at these time-points, a chest 
X-ray should be performed for the purposes of the study. For those participants who cross over, chest imaging should be documented within 7 days prior to Day 1’ of the 
Cross-Over Period, and at Day 29’ (±3 days) of the Cross-Over Period. 
16. Sample must be obtained prior to infusion of study treatment. 
17. Diagnosis of AdV by blood and stool samples will be determined by the central laboratory. Samples will be stored for potential future genotypic or viral load analysis. 
Participants will be followed weekly for viremia and viral load in the stool while symptomatic. The Day 1’ and Day 29’ collections of stool for AdV viral load should be 
collected in all participants, irrespective of GI symptoms. For all other timepoints, these samples are required to be collected if the patient has symptoms (eg, diarrhea). If the 
patient does not have symptoms at these visits, stool viral load should be collected if feasible.  
18. While not a routine evaluation in this study, any participants who manifest clinical signs and/or symptoms of AdV hemorrhagic cystitis should have a urine sample sent to the 
central laboratory for determination of AdV urine viral load. For this subset of participants, AdV urine viral loads should be measured weekly at the central laboratory until 
resolution of hemorrhagic cystitis. 
19. Blood for BKV, CMV, JCV, EBV, and HHV-6 viral load should be collected prior to study treatment administration. 
20. For participants who require intubation and/or undergo bronchoscopy with BAL, a sample of BAL fluid should, when possible, be obtained for AdV viral load determination 
at the central laboratory. For participants who develop symptoms and/or signs of possible AdV-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 AdV viral load determination should, when possible, be sent to 
the central laboratory. 
21. At each time point indicated, blood will be collected into a cell separation tube and processed to generate a PBMC fraction and a plasma fraction. Genomic DNA will be 
extracted from the PBMC fraction. The genomic DNA from PBMC will be cryopreserved for potential future evaluation of VST persistence. The plasma fraction will be 
cryopreserved for potential future evaluation of cytokines and/or other humoral markers of inflammation/immune function. On Day 1’ and Day 15’, the sample should be 
collected pre-dose.  
22. If any participant develops GVHD, that participant 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. 
Abbreviations: AdV = adenovirus; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BAL = bronchoalveolar lavage; CBC = complete blood count; 
CIBMTR = Center for International Blood and Marrow Transplant Research; CMV = cytomegalovirus; COA = clinical outcome assessment; COVID-19 = coronavirus disease 
2019; CSF = cerebrospinal fluid; CT = computed tomography; DNA = deoxyribonucleic acid; ECG = electrocardiogram; EQ-5D = EuroQol – 5 Dimension; ET = Early 
Termination; GVHD = graft versus host disease; HCT = hematopoietic cell transplant; HLA = human leukocyte antigen; ICU = intensive care unit; I/E = inclusion and exclusion; 
IV = intravenous(ly); LFT = liver function test; MAGIC = Mount Sinai Acute GVHD International Consortium; NA = not applicable; PBMC = peripheral blood mononuclear cell; 
qPCR = quantitative polymerase chain reaction; SpO2 = peripheral capillary oxygen saturation; VST = virus-specific T cell. 


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3 
INTRODUCTION  
AlloVir is developing posoleucel, a novel multivirus-specific cellular therapy, to treat and/or 
prevent a number of serious, virus-associated causes of morbidity and mortality after allogeneic 
hematopoietic stem cell transplant (allo-HCT), including those caused by infection or 
reactivation with BK virus (BKV; and the related polyomavirus JC virus [JCV]), 
cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), and 
adenovirus (AdV). 
3.1 
Study Rationale  
Preliminary safety and efficacy data of posoleucel for the treatment of opportunistic viral 
infections common to immunocompromised allo-HCT patients, including AdV, were recently 
generated from a Phase 2 proof-of-concept study (CHARMS). 
This Phase 3 clinical study will assess the safety and efficacy of posoleucel (as compared to 
placebo) for the treatment of AdV infection in pediatric and adult patients receiving standard of 
care following allo-HCT. 
3.2 
Background  
Adenoviruses are a class of double-stranded DNA viruses, with over 50 immunologically distinct 
types that can infect humans. Adenoviruses are associated with a wide range of illnesses, from 
respiratory illnesses, such as the common cold and bronchitis, to illnesses impacting other organ 
systems. While AdV infections are generally controlled by T-cell immunity in 
immunocompetent individuals, infection more frequently progresses to end-organ involvement 
and disseminated disease in individuals who are immunocompromised.   
During the period of immune recovery after allo-HCT, viral infections and reactivations, 
including those with AdV, are an important cause of morbidity and mortality.  
One out of 3 children is reported to have an AdV infection within 6 months post allo-HCT 
(Sedláček 2019). Approximately 6% of adults have been reported to have an AdV infection 
within 6 months post allo-HCT, with a higher incidence in younger adults compared to older 
adults (Sedláček 2019). Progression to AdV disease is associated with significant morbidity and 
mortality rates of up to 50% (Zecca 2019).  
There are no approved antiviral agents for AdV available in the United States (US), Canada, or 
Europe. Cidofovir or brincidofovir are often administered preemptively as treatment for AdV 
infection, although neither are approved for this indication. The optimum doses of cidofovir and 
brincidofovir have not been established, and treatment is associated with various toxicities.  
Brincidofovir is currently in development, but clinical data are limited and brincidofovir has not 
been approved for indications other than treatment of smallpox in the US (June 2021).  
Since recovery of virus-specific T cells (VSTs) after hematopoietic cell transplantation (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 peripheral blood mononuclear cells (PBMCs) procured from healthy pre-screened (for 


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infectious agents and disease risk factors as mandated by Food and Drug Administration (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 human leukocyte antigen (HLA)-
matched “off-the-shelf” product.  
Posoleucel is a VST product that is specific for 5 viruses (AdV, BKV, CMV, EBV, and HHV-6). 
Since posoleucel is only partially matched with the recipient and donor cells, posoleucel cells are 
intended to circulate only until the patient regains immunocompetence following HCT 
engraftment and immune system repopulation. Therefore, posoleucel is 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.  
A detailed description of the in vitro testing of posoleucel and available clinical data are 
provided in Sections 5 and 6, respectively, of the Investigator’s Brochure (IB). 
3.3 
Benefit/Risk Assessment  
Known and potential benefits and risks associated with participation in this study are 
summarized below. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events of posoleucel may be found in the Investigator’s Brochure. 
3.3.1 
Potential Benefits  
A serious unmet medical need exists for patients experiencing AdV infection following allo-
HCT. There are no FDA-, Health Canada-, 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 are associated with significant adverse effects. The CHARMS 
study and other related clinical studies strongly suggest that posoleucel 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 posoleucel efficacy in 
multiple opportunistic viral infections in allo-HCT patients, and its safety profile has the 
potential to be significantly better than that of standard, and inadequately effective, antiviral 
therapy. 
3.3.2 
Potential Risks  
The main potential risks of administration are inflammation at sites of disease or graft versus 
host disease (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.  
Studies of donor-derived VSTs suggest that VSTs do not persist in patients who receive 
methylprednisolone in doses of 1 mg/kg/day. Therefore, if participants develop severe 
inflammatory reactions thought to be attributable to posoleucel, a therapeutic option is to 
administer methylprednisolone (1 to 2 mg/kg/day). In patients who develop skin rash or skin 
GVHD, excellent responses have been seen with administration of topical steroids. 


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As with other biological therapies delivered by IV infusion, possible side effects of posoleucel 
infusion include allergic reaction (anaphylaxis), decreased oxygenation, nausea/vomiting, 
arrhythmia, and hypotension. 
All participants enrolled in the study (including children) are expected to have venous access 
catheters in place for both infusion and blood sampling relating to the treatment of their 
underlying disease and associated HCT procedures. Since study-related collection of blood 
samples and infusion of study treatment (posoleucel or placebo) will utilize catheters already in 
place for routine clinical care, there is minimal incremental risk posed by these study-related 
procedures. A detailed breakdown of the timepoints and blood volumes to be collected during 
the course of this study is provided in the Laboratory Manual. Since this study will enroll both 
adult and pediatric participants, there are different sampling schemes (and associated volumes) 
based on the participant’s 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 wherever possible, and in some cases (eg, pediatric participants weighing <20 kg) 
collection of blood samples at certain timepoints has been eliminated entirely. This has been 
done in a manner that is expected to maintain the scientific integrity of the study while 
minimizing the risks to participants.  






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• To evaluate the persistence of posoleucel 
cells. 
• Persistence of posoleucel cells. 
• To determine the viral re-activation and 
disease occurrence due to BK virus (BKV), 
cytomegalovirus (CMV), human herpesvirus 
6 (HHV-6), Epstein-Barr virus (EBV), or 
John Cunningham virus (JCV). 
• Proportion of participants who develop 
viremia and/or clinical disease (per 
Investigator assessment) by Day 29 (due to 
BKV, CMV, HHV-6, EBV, and/or JCV) for 
those participants without viremia at 
randomization. 
• Proportion of participants with resolution of 
viremia by Day 29 (due to BKV, CMV, 
HHV-6, EBV, and/or JCV) for those 
participants with viremia at randomization. 
• To evaluate non-relapse and all-cause 
mortality. 
• Non-relapse mortality1 at Week 24. 
• All-cause mortality at Week 24. 
• Death due to AdV disease. 
• To determine the percent of participants who 
have clearance of AdV in a) stool, and b) 
nasopharyngeal swab at Day 29. 
• Proportion of participants with undetectable 
AdV viral load (less than LLOQ) in a) stool, 
and b) nasopharyngeal swab at Day 29. 
• To assess the effect of posoleucel on time to 
resolution of AdV in stool. 
• Time to undetectable AdV viral load (less 
than LLOQ) in stool. 
• To determine the percent of participants 
with a decrease in AdV viremia of at least 2 
log10 copies/mL AdV DNA from 
randomization at Day 29. 
• Proportion of participants with a decrease in 
AdV viremia of at least 2 log10 copies/mL 
AdV DNA from randomization at Day 29. 
• To explore the correlation between 
magnitude of AdV viremia and progression 
or non-relapse mortality1. 
• Comparison of AdV viral load versus 
progression/non-relapse mortality1. 
• To explore the correlation between 
clearance of AdV viremia and progression 
or non-relapse mortality1. 
• Comparison of the rates of progression/non-
relapse mortality1 in those participants who 
demonstrate AdV viremia clearance versus 
those who do not. 
• To assess the age-appropriate impact on 
quality of life 
• Change in the European Quality of Life 5 
dimensions (EQ-5D) at Day 29 and 
Week 24. 
1. Non-relapse mortality is defined as death without relapse/recurrence post allo-HCT. 
Abbreviations: AAUC = time-averaged area under the concentration-time curve; AdV = adenovirus; Aes = adverse 
events; AESIs = adverse events of special interest; allo-HCT = allogeneic hematopoietic stem cell transplant; BKV = 
BK virus; CMV = cytomegalovirus; CRS = cytokine release syndrome; EQ-5D = European Quality of Life 5 
dimension; GVHD = graft versus host disease; HHV-6 = human herpesvirus 6; JCV = John Cunningham virus; 
LLOQ = lower limit of quantitation; qPCR = quantitative polymerase chain reaction; SoC = standard of care. 


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5 
STUDY DESIGN  
5.1 
Overall Design  
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the 
safety and efficacy of posoleucel as compared to placebo for the treatment of AdV infection in 
pediatric and adult recipients of HCT with AdV infections receiving SoC.  
Approximately 82 participants at approximately 50 clinical sites in the US, Europe, and Canada 
who meet all of the inclusion criteria and none of the exclusion criteria may be enrolled into the 
study and randomized 
to receive posoleucel or placebo. Randomization will be stratified 
 
 
 It is expected that no more than 30% of participants, but at least 10% of participants, 
will be ≥18 years of age.  
Enrollment of participants <1 year of age will occur once preliminary safety data are available 
from 5 participants ≥1 and ≤6 years of age. On 16May2023, the DSMB reviewed data from 6 
participants aged 1-6 years that have completed through D29 and recommended opening 
enrollment to patients <1 year of age. An additional meeting will be held once 6 patients <1 year 
old have been enrolled and completed through D29 of the study.  
Posoleucel is to be administered at a fixed cell dose based on weight, as  sequential infusions 
separated by 
(see Section 7.1).  
The Primary Study Period is 4 weeks (28 days) for evaluation of efficacy, including the primary 
endpoint, plus 20 weeks for safety follow-up, for a total study duration of 24 weeks. For 
participants who cross over, the Cross-Over Period is 4 weeks (28 days), plus 20 weeks for 
safety follow-up. Participants who experience recurrence and receive an additional dose will 
have safety follow-up for 20 weeks after the additional dose of study treatment.  
At Day 29, all participants will be assessed for the primary endpoint, virologic response.  
Option for Cross-Over 
Participants who progress to active target organ disease or whose existing target organ disease 
progresses (assessed by the Investigator and Sponsor Medical Monitor and based on the criteria 
in Appendix 8) between Day 29 and Week 10 will be considered to have experienced 
progression and will have the option to be crossed over to the alternate treatment arm. 
Participants can cross over before Day 29 only if they progress as adjudicated by the 
Adjudication Committee. For potential cases of premature cross-over (ie, prior to Day 29), 
participants will be expected to have received both infusions of study treatment before evaluation 
by the Adjudication Committee. Cross-over participants will receive the alternate treatment to 
which they were originally randomized, posoleucel or placebo ( sequential infusions separated 
by 
 but study treatment will remain blinded. Participants must meet the following 
eligibility criteria to cross-over: participant must not have evidence of acute GVHD Grade 3 or 
higher (Exclusion Criterion 1), must not be receiving ongoing therapy with high-dose systemic 
corticosteroids >0.5 mg/kg/day prednisone or equivalent unless approved by Medical Monitor  
(Exclusion Criterion 2) and must not have experienced a severe infusion-related reaction (Grade 
≥3) with the prior doses of study treatment (posoleucel or placebo).  


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If the participant receives any antiviral drugs in violation of the protocol during the study, that 
participant will be included in the primary analysis, but will not be eligible for cross-over. 
Follow-up will be continued for safety and persistence of the virus-specific T cells (VSTs). 
Participants must meet all of the cross-over eligibility criteria by Week 10 of the Primary Study 
Period to enter the Cross-Over Period. A new baseline (Day 1’ of the Cross-Over Period) will be 
established at the time of the first cross-over infusion. At Day 29’ of the Cross-Over Period, 
participants will be assessed for clinical and virologic response. The participants will then have 
20 weeks of safety follow-up, for a total duration of 24 weeks for the Cross-Over Period. The 
maximum study duration for participants who cross over is 34 weeks, including up to 10 weeks 
in the Primary Study Period and 24 weeks in the Cross-Over Period.  
Participants who cross over are not eligible to receive treatment for recurrence (described 
below). 
Recurrence 
Participants who demonstrate viral clearance by Day 29 of the Primary Study Period but later 
exhibit a clinically significant recurrence of AdV viremia (ie, ≥10,000 copies/mL AdV DNA at 
the central laboratory) and/or progression of or to active organ disease, will be eligible for an 
additional dose of the last received therapy (posoleucel or placebo) for recurrence prior to 20 
weeks. These participants will continue to have safety follow-up for an additional 20 weeks after 
administration of the additional dose. The visit in which the participant receives the additional 
dose for recurrence should mimic the assessments performed on 
 Participants who 
receive an additional dose for recurrence will be monitored using the schedule as specified in the 
Primary Study Period schedule of events starting at the Week 5 visit, which should occur 1 week 
after infusion of the additional dose. This applies even if the participant completed any of these 
visits prior to receiving the additional dose. 
A summary of the study design is shown in Figure 1. 




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5.3 
End of Study Definition  
A participant is considered to have completed the study if he/she has completed the Week 24 
visit of the Primary Study Period (for participants who do not cross over) or the Week 24’ visit 
of the Cross-Over Period (for participants who cross over). 
The end of the study is defined as completion of the final visit for the final participant. 
All participants in this study will be approached for enrollment in a long-term registry study. 
5.4 
Scientific Rationale for Study Design  
Patients of all ages are eligible for enrollment in this clinical study. The inclusion of pediatric 
patients in this study is justified for the following reasons: 1) one out of 3 children develop an 
AdV infection within 6 months of allo-HCT (Sedláček 2019); 2) progression to AdV disease is 
associated with significant morbidity and mortality rates of up to 50% in pediatric allo-HCT 
recipients (Zecca 2019); 3) there are no approved, efficacious antiviral therapies for the treatment 
of AdV infection; and 4) in the Phase 2 CHARMS study, 17 of 58 patients enrolled (29%) were 
<18 years of age, with the youngest age of 2 years old (Tzannou 2017). This previous clinical 
pediatric experience with posoleucel supports the inclusion of patients <18 years of age in this 
study. 
The use of placebo in this clinical study is justified for the following reasons: 1) since the natural 
history of AdV infection in the allo-HCT population is variable and not readily predictable, a 
randomized controlled trial with placebo allows for an unbiased evaluation of the efficacy and 
safety of posoleucel, and 2) 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 AdV infection. 
The cross-over design is justified for the following reasons: 1) allows a larger sample size of 
participants treated with posoleucel without increasing the number of enrolled participants; and 
2) allowing participants to cross over ensures that blinding can be maintained until the study is 
complete.  
For a variety of viral diseases, the amount and kinetics of virus levels in blood or plasma has 
been widely accepted as a surrogate for clinical events (eg, human immunodeficiency virus, 
hepatitis B virus, hepatitis C virus). In most cases, the goal of conventional small molecule 
antiviral therapy is suppression of viral replication to undetectable levels. In the recent US FDA 
Guidance Cytomegalovirus in Transplantation: Developing Drugs to Treat or Prevent Disease 
(May 2020), the use of CMV viremia as a validated surrogate endpoint in clinical trials is 
discussed. There is also evidence to suggest that adenoviremia also serves as a suitable surrogate 
endpoint to evaluate the antiviral activity of a cell-based immunotherapeutic anti-AdV agent.  
The body of published data supports the concept that virological suppression translates into 
clinical benefit. This view is also robustly expressed in AdV consensus treatment guidelines such 
as those of ECIL-4 (Matthes-Martin 2012) and EBMT (Hiwarkar 2018), recommending pre-
emptive therapy, which is based on a recognition of the surrogacy of viremia.   
Since there are no approved antiviral therapies for the treatment of AdV, the kinetics of 
therapeutic viremia resolution are not established. Data from the CHARMS study, in which 
patients with persistent and/or recurrent viral infections were treated with posoleucel provide an 
indication of viral load kinetics that have informed the selection of the Day 29 post-treatment 


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timepoint for the evaluation of the primary efficacy outcome in the current study. In the 
CHARMS study, there were 13 participants with informative AdV viremia data; 9 of these 
participants demonstrated declines in viremia after administration of posoleucel. In all cases, 
these viremia responses were apparent by 4 weeks (ie, 28 days) of treatment with posoleucel. 
Accordingly, the evaluation at Day 29 (ie, 28 days after the initial infusion of 
posoleucel/placebo) has been selected for the primary efficacy outcome in the current study. 
It is generally accepted that the magnitude and duration of AdV viremia contribute to the 
development of clinically relevant infections (Sedlacek 2019), and that the overall AdV viral 
burden (extent of viremia over time) is predictive of all-cause mortality in pediatric HCT 
recipients with AdV viremia (Zecca 2019). The levels of AdV viremia required for inclusion in 
this study have been selected because these are thresholds that place patients at risk for 
development of disseminated AdV disease and increased mortality (Hiwarkar 2018, Mynarek 
2014) and are less likely to be associated with spontaneous resolution. Importantly, AdV unlike 
CMV or EBV, is a lytic virus so risk of recurrent infections once the virus has cleared is 
considered to be low. Nonetheless, to assess durability of response longer term data on viremia 
as well as signs and symptoms will be captured.  
The durability of response in viremia will be evaluated after the Day 29 timepoint throughout the 
remainder of the study. This will be accomplished at the protocol-specified evaluations 
(including viral load determinations at the central laboratory) at Weeks 5, 6, 10, 16, and 24, and 
will be addressed specifically by the following two secondary efficacy endpoints: a) To 
determine the percent of participants who develop target organ AdV disease (eg, lower tract 
respiratory disease documented radiographically, AdV-associated hemorrhagic cystitis, severe 
hepatitis) or whose target organ disease progresses during the study, and b) To evaluate the 
proportion of participants who have recurrence of viremia (≥10,000 copies/mL AdV DNA) 
and/or target organ disease during the study (among participants who had clearance of AdV 
viremia). 
5.5 
Justification for Dose  
Posoleucel is to be administered at a fixed cell dose based on weight. Fixed, weight-based doses 
were selected based on data from previous clinical studies in which posoleucel was well 
tolerated, safe, and effective. 
The dose of posoleucel 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 
per infusion. A 
retrospective analysis of actual doses administered in the CHARMS study demonstrated that, on 
average, patients who weighed 
 
 
 
 
The VST line chosen for the second infusion of posoleucel may come from a different donor 
than the first infusion, depending on the AdV viral load following the first dose of posoleucel 
(see Section 7.1 for details). Providing posoleucel cells from a different donor in participants 
with a higher viral load after the first dose will increase the repertoire of T cells provided, which 
may increase the likelihood of responding to posoleucel treatment. 


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6 
STUDY POPULATION  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
6.1 
Inclusion Criteria  
Patients must meet all of the following criteria in order to be eligible for enrollment into the 
study. Screening laboratory criteria can be confirmed using local or central laboratories. 
1. Male or female of any age.   
2. Has undergone allogeneic (including umbilical cord) cell transplantation ≥21 days prior 
to dosing and has demonstrated engraftment with an absolute neutrophil count 
>500/mm3, AND has one of the following: 
a. AdV viremia DNA ≥10,000 copies/mL at screening, OR 
b. Two consecutive and rising AdV viremia DNA results of ≥1,000 copies/mL at 
screening, AND  
i. has absolute lymphocyte count <180/mm3, OR  
ii. has received T cell depletion, OR 
iii. had a cord blood transplant. 
3. Males and females of childbearing potential who engage in heterosexual intercourse must 
agree to use contraception as detailed in Appendix 5 of this protocol and refrain from 
donating sperm or eggs for at least 90 days after treatment completion. 
4. Willing and able to provide signed informed consent. 
5. Has an HLA type matching with at least 1 suitably matched and available posoleucel 
VST line for infusion.  
6.2 
Exclusion Criteria  
Patients who meet any of the following criteria will be excluded from participation in the study: 
1. Grade 3 or higher acute GVHD (see Appendix 6 for information on acute GVHD grading 
and severity). 
2. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone dose 
>0.5 mg/kg/day or equivalent).  Patients actively undergoing corticosteroid tapering 
during Screening may randomize and dose once they have reached ≤ 1.0 mg/kg/day with 
Medical Monitor approval, with the expectation that the corticosteroid taper will 
continue. 
3. Has either of the following laboratory parameters at screening: 
a. Aspartate aminotransferase and alanine aminotransferase serum levels ≥5 times 
the upper limit of normal (ULN), OR 
b. Direct bilirubin serum levels ≥3 times the ULN. 


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Exception: Patients with elevations of these laboratory parameters may be included if 
these elevations are attributed to AdV hepatitis and are not considered attributable to 
other etiologies. 
4. Relapse of primary malignancy, or any other active malignancy, except for 
non-melanoma skin cancer. Malignancies that are slow growing and/or stable may be 
allowed with Medical Monitor approval. 
5. Grade 4 diarrhea (ie, life-threatening consequences with urgent intervention indicated) 
regardless of attribution ongoing or within 7 days prior to randomization. 
6. Uncontrolled viral (other than AdV), bacterial, or fungal infection(s) leading to 
hemodynamic instability or radiologic or laboratory evidence attributable to worsening 
disease. 
7. Requirement for fraction of inspired oxygen (FiO2) >0.5 (ie, 50%) to maintain arterial 
oxygen saturation >90% (via pulse oximetry) or need for mechanical ventilation, except 
for planned procedures or surgeries with Medical Monitor approval. For guidance on 
estimating fraction of inspired oxygen, see Appendix 9. 
8. Prior therapy with anti-thymocyte globulin, alemtuzumab (Campath®), or other 
immunosuppressive T cell monoclonal antibodies within 28 days prior to dosing. 
9. Prior donor lymphocyte infusion or CD34+ stem cell infusion within 21 days prior to 
dosing. 
10. Use of vasopressors within 7 days prior to randomization. 
11. Use of any investigational antiviral agent, including brincidofovir, within 7 days prior to 
randomization. Maribavir and letermovir for CMV will be allowed. 
12. Pregnant or lactating female unwilling to discontinue nursing prior to randomization. 
13. Any condition that, in the opinion of the Investigator, would compromise the safety of the 
patient, would prevent full participation in this study, or would interfere with the 
evaluation of any study endpoints. 
14. History of severe (Common Terminology Criteria for Adverse Events [CTCAE] Grade 
≥3) allergy to any component of posoleucel (including human serum albumin and 
dimethyl sulfoxide) or history of severe (CTCAE Grade ≥3) prior reactions to blood 
product transfusions. 
15. Positive for SARS-CoV-2 virus at screening. Exception: Patients who test positive for 
SARS-CoV-2 at screening and who have a recent prior positive test may be enrolled if 
they have no clinical or radiological manifestations of COVID-19 and if the Investigator 
and Medical Monitor concur on their enrollment. 
6.3 
Lifestyle Restrictions  
There are no lifestyle restrictions for participants in this study. 
6.4 
Screen Failures  
Screen failures are defined as patients who consent to participate in the clinical study but are not 
randomized into the clinical study. A minimal set of screen failure information is required to 


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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, and any 
serious adverse events (SAEs). 
Rescreening may be permitted following discussion with the Sponsor. 
7 
TREATMENTS  
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
7.1 
Treatments Administered  
Participants in the study will receive posoleucel or placebo. Posoleucel is a third-party, donor-
derived, “off-the-shelf,” VST product with specificity for BKV, AdV, CMV, EBV, and HHV-6 
(with additional cross-reactive specificity for JCV) that is cryopreserved and ready for immediate 
use. 
Study Treatment 
Name: 
Posoleucel 
Placebo 
Dosage 
formulation: 
 
Posoleucel will be frozen in a 
cryopreservation medium 
containing 
 
 
 
 
 
Cryopreservation medium 
containing 
 
 
 
 
 
Unit dose 
strength(s)/Dosage 
level(s): 
 
 
  
Participants who weigh <40 kg 
will receive 
posoleucel cells 
(
 while participants 
who weigh 40 kg will receive 
cells 
  
 
0 cells/mL in a volume of 
approximately 2.5 mL 
Participants who weigh <40 kg 
will receive a volume equivalent to 
posoleucel cells 
 
 while participants who 
weigh 40 kg will receive a 
volume equivalent to 
cells 
(
  


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Study Treatment 
Name: 
Posoleucel 
Placebo 
For the second dose  
(Day 12-18/Day 12’-18’): 
• If AdV viral load decrease from 
baseline is ≥0.5 log 10 
copies/mL AdV DNA at Days 8 
or 11 (Days 8’ or 11’), the 
participant will receive a 
second dose with the same VST 
line as the first dose. 
• If AdV viral load decrease from 
baseline is <0.5 log 10 
copies/mL AdV DNA at Days 8 
or 11 (Days 8’ or 11’), the 
participant will receive a 
second dose with a new VST 
line from a different donor. 
For the second dose  
(Day 12-18/Day 12’-18’): 
• If AdV viral load decrease from 
baseline is ≥0.5 log 10 
copies/mL AdV DNA at Days 8 
or 11 (Days 8’ or 11’), the 
participant will receive a 
second dose with the same 
placebo lot as the first dose. 
• If AdV viral load decrease from 
baseline is <0.5 log 10copies/mL 
AdV DNA at Days 8 or 11 
(Days 8’ or 11’), the participant 
will receive a second dose with 
placebo from a different lot. 
Participants will receive the same 
dose for both infusions (first and 
second doses) of each study 
period. 
Participants will receive the same 
dose for both infusions (first and 
second doses) of each study 
period. 
Route of 
Administration  
IV (via central or peripheral line) over approximately 
 as a 
slow push 
Dosing 
instructions: 
 
Premedication is not required, except for participants with a prior 
history of reaction to blood products who may receive premedication 
with 0.25 to 0.5 mg/kg (maximum dose of 25 mg) diphenhydramine (IV 
or oral) (or a similar antihistamine preferred by the clinical site), and/or 
5 to 10 mg/kg (maximum dose of 650 mg) acetaminophen (IV or oral) 
prior to study treatment administration. If alternative doses of 
diphenhydramine and/or acetaminophen are routinely used for the 
premedication of infusion reactions at the clinical site, then these doses 
may be used. Premedication with corticosteroids is prohibited. 
 
Refer to the Cell Therapy Manual for instructions regarding thawing 
and preparation of IP 
Packaging and 
Labeling 
Study treatment will be provided in 6.0 mL cryovials. Each cryovial will 
be labeled as required per country requirement.  
Manufacturer 
AlloVir 
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Posoleucel cell lines will be selected for each participant based on an 
 
 
 
The appropriate drug product (ie, the VST lines for infusion) for administration will be selected 
using a software program (CytoMatch), 
 
 
 
 
 
 
 
 
 
 
  
 
 
For participants whose AdV viral load as determined by the Central Laboratory has decreased 
≥0.5 log 10 copies/mL AdV DNA between Day 1 and Day 8 or 11, the second dose will be from 
the same VST line/placebo lot as the first dose. When possible, the Day 11 value should be used 
to make this determination; however, if a Day 11 value is not available, the Day 8 value can be 
used. For participants whose AdV viral load has decreased <0.5 log 10 copies/mL AdV DNA 
between Day 1 and Day 8 or 11, the second dose will be with a new VST line from a different 
donor or placebo from a different lot. When possible, the Day 11 value should be used to make 
this determination; however, if a Day 11 value is not available, the Day 8 value can be used. In 
that case, the VST line chosen for the participant’s second infusion will be the VST line with the 
next-best match according to the CytoMatch hierarchy as described above and will come from a 
different donor than the first VST line infused, while maintaining a threshold of at least 2 HLA 
allele matches between the VST line and the virus-infected recipient. The choice of second dose 
for participants who enter the Cross-Over Period will use the same criteria (with AdV viral load 
assessment on Day 11’ [or Day ‘8, if Day 11’ value is not available] to support the second dose 
on Day 15’). 
In the unlikely event that a suitable VST line for the second infusion cannot be identified in the 
bank, a second dose of the first VST line infused will be substituted for the participant’s second 
infusion. 
For participants who receive an additional dose for recurrence, the additional dose will be from 
the same VST line or placebo lot and include the same number of cells as the second dose. An 
additional dose for recurrence can only be administered after Day 29 of the Primary Study Period 
(the primary endpoint), but prior to 20 weeks. Participants who receive an additional dose for 
recurrence are not eligible for subsequent cross-over, and participants who have previously 
entered the Cross-Over Period are not eligible for a subsequent additional dose. 
Once the lots of drug product have been selected, the treating physician will review and approve 
documentation that accompanies the drug product shipment prior to dose administration. 


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Randomization of patients to posoleucel versus placebo will occur only after VST line matching 
and selection has been confirmed (to satisfy inclusion criteria).  
7.1.1 
Study Drug Administration  
For complete instructions on study drug administration, including the thawing of the product, 
please refer to the Cell Therapy Manual.  
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. 
• Participants must remain on continuous pulse oximetry for 30 minutes after the end of the 
infusion. 
• Vital signs will be monitored at the end of infusion, and at 15, 30, 45, and 60 minutes after 
the end of the infusion. 
All findings must be recorded in the electronic case report form (eCRF). 
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 7.7.1 for additional information. 
If a participant experiences an infusion reaction, then 0.25 to 0.5 mg/kg (maximum dose of 
25 mg) diphenhydramine (IV or oral) and/or 5 to 10 mg/kg (maximum dose of 650 mg) 
acetaminophen (IV or oral) may be administered as treatment (even if received as 
premedication). If diphenhydramine is not available or is not routinely used at the clinical site, an 
alternative antihistamine may be used instead. If alternative doses of diphenhydramine and/or 
acetaminophen are routinely used for the treatment of infusion reactions at the clinical site, then 
these doses may be used. In the case of suboptimal control of an infusion reaction or the need to 
use corticosteroids for treatment of an infusion reaction, doses of 0.5mg/kg/day of prednisone 
or equivalent should be considered first. 
7.2 
Dose Modification  
No dose modifications are permitted. Reference Section 8.1 for Discontinuation of Study 
Treatment Criteria.  
7.3 
Method of Treatment Assignment  
Participants who meet all of the inclusion criteria and none of the exclusion criteria will be 
randomized to the study prior to Day 1 of the Primary Study Period. Participants 
 
 
 
 
7.4 
Blinding  
The Sponsor designee (eg, interactive response technology [IRT] vendor) will have a designated 
randomization administrator who will maintain the randomization codes in accordance with 


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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). 
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 AE 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 patient’s 
identification, the reason for breaking the blind, and the date and time for breaking the blind.  
7.5 
Preparation/Handling/Storage/Accountability  
Posoleucel (or placebo) is stored in the vapor phase of liquid nitrogen in a continuously 
monitored storage freezer. 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 shipper 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. 
All material containing posoleucel (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 VST line to the third-party PBMC donor 
from whom it originated. These records will be maintained for 30 years after expiry for each 
VST line. 
Detailed records will be maintained to allow for accurate accountability of posoleucel and 
placebo as per applicable Sponsor and clinical site procedures. For further details and 
specifications, see the Cell Therapy Manual. 
7.6 
Treatment Compliance  
Posoleucel (or placebo) will be administered only IV and only under the direct supervision of 
clinical study personnel at the site. 


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7.7 
Concomitant Therapy  
Any medication or vaccine (including over-the-counter or prescription medicines and/or GVHD 
prophylaxis) that the participant has received within 30 days before screening, is receiving at the 
time of enrollment, or receives during the study must be recorded. The patient’s conditioning 
regimen for most recent HCT should also be recorded, even if it is outside of the 30 day window.  
All concomitant therapy outlined above will be recorded along with:  
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Fluids, electrolytes, vitamins and supplements, mouth care, and laxatives, as well as “as needed” 
medications, do not need to be recorded during screening unless they are used to treat an AE. 
“As needed” medications can be reported as 1 item without detailing the components. The 
Medical Monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. 
7.7.1 
Permitted Concomitant Therapy  
Participants in both treatment arms will continue to receive SoC per their Treating Physician. 
Any medications, therapies, or procedures performed as SoC will be documented in the 
appropriate eCRF.  
Clinically available (non-investigational) antiviral agents (eg, acyclovir, ganciclovir, foscarnet, 
maribavir, letermovir) and the use of intravenous immunoglobulin are permitted during the 
study. For this study, the use of maribavir and letermovir to treat CMV infections will be 
considered non-investigational, regardless of the regional regulatory approval status. 
Cidofovir is not currently approved for the treatment of AdV infection in any regions conducting 
this trial. Given the unknown efficacy of cidofovir against adenovirus infection and known 
toxicity (e.g. nephrotoxicity) associated with its use, it is recommended that patients do not 
initiate or continue the use of cidofovir at the time of enrollment into the study. Cidofovir may be 
initiated or stopped at any time based on investigator judgment during the study. The dose and 
regimen of cidofovir is not restricted but must be documented in the EDC as a concomitant 
medication if used.  
7.7.2 
Excluded Concomitant Therapy  
All participants may receive available supportive therapy with approved treatments.  
The use of investigational antiviral agents is prohibited. Whereas brincidofovir (Tembexa®) is 
approved in the US for the treatment of human smallpox disease (and is specifically not 
indicated for the treatment of any other diseases), it is considered an investigational antiviral 
agent for this study and is therefore prohibited.   
T cell ablative therapies, such as ATG, alemtuzumab (Campath®), or other immunosuppressive T 
cell-targeted monoclonal antibodies, are prohibited within 28 days prior to dosing and during the 
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Whereas it is recognized that investigators and treating physicians will as part of their standard 
of care, where feasible, reduce immunosuppression in their patients with AdV infection, there are 
no specific guidelines on how this should be achieved. It should be noted in this context that 
ongoing therapy with high-dose systemic corticosteroids (eg, > 0.5 mg/kg/day prednisone 
equivalents) may impact the efficacy of posoleucel and is prohibited during the course of the 
study unless medically indicated. 
Prior donor lymphocyte infusions (DLI) or CD34+ stem cell infusion within 21 days prior to 
dosing is exclusionary (Exclusion Criterion 9).  
Any participants who receive any hematopoietic stem cell products after randomization will be 
discontinued from study treatment but will continue to be followed in the study. 
7.8 
Treatment after the End of the Study  
Participants will not receive study treatment (posoleucel or placebo) after completion of the 
study. 
8 
DISCONTINUATION/WITHDRAWAL CRITERIA  
8.1 
Discontinuation of Study Treatment  
Participants will be discontinued from study treatment if any of the following criteria are met: 
• Development of Grade 3 or higher acute GVHD or a Grade 3 to 4 non-hematologic 
adverse event between the first and any subsequent dose of posoleucel or placebo that is 
considered related to study treatment. 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 participation in the study 
ends. 
• Occurrence of any medical condition or circumstance that exposes the participant to 
substantial risk. 
• Any SAE, clinically significant adverse event, severe laboratory abnormality, intercurrent 
illness, or other medical condition that indicates to the Investigator that continued dosing 
of study treatment is not in the best interest of the participant. 
• Pregnancy. 
• Requirement for prohibited concomitant medication. 
• Participant (or parent or legal guardian) chooses not to receive any further doses of study 
treatment.  
If any of the above criteria are met, every effort should be made to keep the participant in the 
study and continue follow-up. 


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8.2 
Withdrawal from the Study  
Participation in this clinical study may 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. 
• Participant failure to comply with protocol requirements or study-related procedures. 
• Termination of the study by the Sponsor or the regulatory authority. 
If a participant withdraws prematurely from the study due to the above criteria or any other 
reason, study staff should make every effort to complete an Early Termination Visit (see the SoA 
in Section 2). The reason for participant withdrawal must be documented in the eCRF. 
Withdrawn participants will not be replaced. 
8.3 
Lost to Follow Up  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study. 
• Before a participant is deemed lost to follow up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  


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9 
STUDY ASSESSMENTS AND PROCEDURES  
• Study procedures and their timing are summarized in the SoA (Section 2).  
• Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
treatment. 
• Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.  
• Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA. 
• The maximum amount of blood collected from each participant over the duration of the 
study, including any extra assessments that may be required, is based on weight and detailed 
in the Laboratory Manual. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples. 
9.1 
Efficacy Assessments  
9.1.1 
Viral Load Detection Using Quantitative Polymerase Chain Reaction  
Samples will be collected for viral load detection as shown in the SoA (Section 2) and 
Appendix 3.  
Viral load of AdV in blood, stool, and nasopharyngeal samples will be measured by qPCR, 
performed by the central laboratory during the study. Blood and stool samples will be stored for 
potential future virus genotypic or viral load analysis.  
During Screening, blood specimens may be collected locally in addition to a central laboratory 
sample.  Local laboratory results available up to 5 days prior to or during screening may be used 
to initiate screening activities and support eligibility determination. For the inclusion criterion 
requiring two consecutive and rising AdV viremia results exceeding 1,000 copies/mL, the two 
consecutive viremia results used to determine eligibility must have been assayed at the same 
laboratory, preferably the central laboratory.  Participants may be randomized and dosed (with 
Medical Monitor approval) based on local laboratory AdV viremia results. This process is 
expected to expedite the randomization and dosing of participants whose clinical status may 
rapidly deteriorate.  
All study analyses will continue to be performed using viral load data from the central 
laboratory.  
While not a routine evaluation in this study, any participants who manifest clinical signs and/or 
symptoms of AdV hemorrhagic cystitis should have a urine sample sent to the central laboratory 


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for determination of AdV urine viral load. For this subset of participants, AdV urine viral loads 
should be measured weekly at the central laboratory until resolution of hemorrhagic cystitis. 
For participants who require intubation and/or undergo bronchoscopy with bronchoalveolar 
lavage (BAL), a sample of BAL fluid should, when possible, be obtained for AdV viral load 
determination at the central laboratory. For participants who develop symptoms and/or signs of 
possible AdV-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 AdV viral load determination should, when possible, be 
sent to the central laboratory. In all cases, BAL and CSF samples required for routine clinical 
care of the patient take precedence over these study-related evaluations.  
Infections with BKV, CMV, JCV, EBV, and HHV-6 contribute to significant morbidity and 
mortality in allo-HCT recipients, and posoleucel also targets these 5 viruses. Therefore, viral 
load of BKV, CMV, JCV, EBV, and HHV-6 will also be assessed in this study by qPCR from 
blood samples.  
9.1.2 
Target Organ Disease  
Participants with any one of the following manifestations will be adjudicated by the Adjudication 
Committee for target organ disease: 
• Clinically significant AdV viremia 
• AdV pneumonia 
• AdV hepatitis 
• AdV enterocolitis 
• AdV pancreatitis 
• AdV hemorrhagic cystitis 
• AdV nephritis 
• AdV encephalitis/myelitis 
• AdV retinitis/ocular disease 
• AdV carditis 
• Death due to AdV disease 
These manifestations are defined in Appendix 8. 
Participants with BKV, CMV, JCV, EBV, and/or HHV-6 infection, which are also targeted by 
posoleucel, should be similarly assessed for progression of infection to target organ disease or 
worsening of target organ disease by the investigator. These manifestations will not be 
adjudicated by the committee.  
9.1.3 
Radiological Imaging  
The presence or absence of abnormalities consistent with lower respiratory tract infection on 
chest X-ray and/or CT scan as assessed by the local radiologist should be documented at 


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screening (obtained no more than 10 days prior to dosing) and at Day 29 (±3 days). If no routine 
clinical radiological imaging of the chest is available at either of these timepoints, a chest X-ray 
should be obtained (chest CT scan is not a study-mandated procedure; however, the results of 
chest CT scan[s] performed as part of a participant’s standard clinical care may be used for the 
purposes of the study. For those participants who cross over, chest imaging as described above 
should be documented within 7 days prior to Day 1’ of the Cross-Over Period and at Day 29’ (±3 
days) of the Cross-Over Period. If the Day 29 imaging from the Primary Study Period falls 
within the 7-day window prior to cross over, this imaging need not be repeated prior to the 
participant entering the Cross-Over Period (ie, the Day 29 imaging will serve as the baseline 
imaging for the Cross-Over Period). All chest X-rays and/or CT scans will also be submitted for 
central reading, which will be used for analysis purposes. 
9.1.4 
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. The 5-level EQ-5D (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 patient is asked to indicate his or her health state by checking the box 
next to the most 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 Youth 
(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 patient’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.” 
9.2 
Adverse Events  
The definitions of an adverse event (AE) and an SAE can be found in Appendix 4. 
All AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant’s legally authorized representative).  
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
participant to discontinue the study treatment (see Section 8.1).  
9.2.1 
Time Period and Frequency for Collecting AE and SAE Information  
All AEs and SAEs will be collected from the signing of the ICF until the Week 24 visit (or Week 
24’ visit for participants who cross over) at the time points specified in the SoA (Section 2). 


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Medical occurrences that begin before obtaining informed consent will be recorded on the 
Medical History/Current Medical Conditions section of the eCRF, not the AE section. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Appendix 4. The Investigator will submit any updated SAE data to the Sponsor within 
24 hours of awareness. 
Investigators are not obligated to actively seek AE or SAE in former study participants. 
However, if the Investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event to be reasonably related to 
the study treatment or study participation, the Investigator must promptly notify the Sponsor. 
9.2.2 
Method of Detecting AEs and SAEs  
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 4. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.  
9.2.3 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, 
the event is otherwise explained, or the participant is lost to follow-up (as defined in 
Section 8.3). Further information on follow-up procedures is given in Appendix 4. 
9.2.4 
Regulatory Reporting Requirements  
• Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study treatment under clinical investigation are met.  
• The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and Investigators. 
• An Investigator who receives an Investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from the Sponsor will 
review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
• Investigator safety reports must be prepared for SUSARs according to local regulatory 
requirements and Sponsor policy and forwarded to Investigators as necessary. 
9.2.4.1 
Expedited Reporting  
The Sponsor/designee will report all relevant information about SUSARs that are fatal or life 
threatening- as soon as possible to the applicable regulatory and competent authorities in the US 


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and elsewhere, 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 applicable regulatory and competent authorities concerned, 
and the Central Ethics Committee concerned 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. 
9.2.5 
Pregnancy  
• 
Details of all pregnancies in female participants and female partners of male participants 
will be collected after the start of study treatment and until 90 days after the last dose of 
study treatment. 
• 
If a pregnancy is reported, the Investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor within 24 hours of learning of the pregnancy 
of the female participant or female partner of a male participant after obtaining the necessary 
signed informed consents. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
or elective termination of a pregnancy for medical reasons will be reported as an AE or 
SAE. 
• 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
• 
The female participant or pregnant female partner of a male participant will be followed to 
determine the outcome of the pregnancy. The Investigator will collect follow-up information 
on the female participant or pregnant female partner of a male participant and the neonate 
and the information will be forwarded to the Sponsor. 
• 
Any post-study pregnancy-related SAE considered reasonably related to the study treatment 
by the Investigator will be reported to the Sponsor as described in Section 9.2.4. While the 
Investigator is not obligated to actively seek this information in former study female 
participants or pregnant female partners of male participants, he or she may learn of an SAE 
through spontaneous reporting. 
• 
Female participants who become pregnant will be discontinued from the study treatment 
(see Section 1). 
9.2.6 
Adverse Events of Special Interest  
Adverse events of special interest include acute and chronic GVHD (new onset or worsening of 
existing GVHD), graft failure and rejection, CRS, and infusion-related AEs. Grading criteria for 
GVHD and CRS can be found in Appendix 6 and Appendix 7, respectively. 


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9.2.6.1 
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). 
• 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 investigational product 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 the Special Situations Report 
Form and faxed/emailed to 
 (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: 
 
Telephone (within US): 
 
Telephone (outside US): 
 
Fax: 
 
Email: 
 
9.3 
Safety Assessments  
Safety will be assessed by TEAEs (defined in Appendix 4), clinical laboratory evaluations and 
urinalysis, physical examination, vital signs, ECGs, chest x-ray and/or CT scan, monitoring for 
GVHD and CRS, and pregnancy testing. 
Planned time points for all safety assessments are provided in the SoA (Section 2). 


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9.3.1 
Clinical Laboratory Evaluations  
Blood for clinical chemistry and hematology will be obtained as indicated in Section 2 and sent 
to the central laboratory for evaluation. See Appendix 3 for a complete list of analytes and the 
Laboratory Manual for blood draw volumes and timepoints based on the participant’s weight. 
Screening laboratory criteria can be confirmed using local or central laboratories. 
Urine will be obtained as indicated in Section 2 and sent to each site’s clinical laboratory per 
institutional guidelines for complete urinalysis. See Appendix 3 for a complete list of analytes.  
A serum pregnancy test will be performed at screening for all female participants of childbearing 
potential. A serum or urine pregnancy test will be repeated prior to dosing on Day 1 for females 
of childbearing potential, only if the pregnancy test performed at screening was not completed 
within 48 hours prior to study treatment administration. A serum or urine pregnancy test will be 
performed prior to each additional study treatment administration (if applicable) and at the Week 
10 (Week 10’), Week 16 (Week 16’), Week 24 (Week 24’), and ET visits for female participants 
who are of childbearing potential. See Section 2 and Appendix 3.  
9.3.2 
Vital Signs  
Vital sign measurements will include body temperature, heart rate, respiratory rate, SpO2, and 
systolic and diastolic blood pressure, and will be measured after resting for at least 5 minutes in 
the supine position as indicated in Section 2. 
9.3.3 
Electrocardiograms  
Standard 12-lead ECGs will be performed as indicated in the SoA (Section 2).  
9.3.4 
Physical Examinations  
Physical examinations will be performed, and height and weight will be collected as indicated in 
the SoA (Section 2). The complete physical examination will be performed by either the 
Investigator or a Sub-Investigator who is a physician. New abnormal physical examination 
findings must be documented and will be followed by a physician or other qualified staff at the 
next scheduled visit. 
9.3.5 
Graft Versus Host Disease  
Acute and chronic GVHD will be assessed as indicated in Section 2. If any participant develops 
GVHD, that participant may receive standard GVHD treatment at the discretion of the 
Investigator. 
9.3.5.1 
Acute Graft Versus Host Disease  
Staging and grading of acute GVHD will be reported using Mount Sinai Acute GVHD 
International Consortium (MAGIC) 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 6. 
9.3.5.2 
Chronic Graft Versus Host Disease  
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 6. 


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9.3.6 
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 7. 
9.3.7 
Post-Infusion Monitoring  
Post-infusion monitoring will be performed as indicated in Section 2. 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, 
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. 
Participants must also remain on continuous pulse oximetry for a minimum of 30 minutes after 
the end of the infusion. These monitoring durations are minimum requirements; Investigators 
should remain vigilant for any changes from pre-infusion baseline in vital signs or clinical 
condition, and participants should remain at the clinical site and be monitored for longer than 
these minimum times if abnormalities persist. 
9.4 
Pharmacokinetics  
Pharmacokinetic parameters are not evaluated in this study. 
9.5 
Pharmacodynamics  
Pharmacodynamic parameters are not evaluated in this study. 
9.6 
Genetics  
Genetics are not evaluated in this study. 
9.7 
Biomarkers  
Biomarkers are not evaluated in this study. 
9.8 
Medical Resource Utilization and Health Economics  
Medical resource utilization and health economics data, associated with medical encounters, will 
be collected in the CRF by the Investigator and study-site personnel for all participants 
throughout the study. Protocol-mandated procedures, tests, and encounters are excluded.  
The data collected include: 
• Number of hospitalizations 
• Duration of hospitalization (total days, including duration by wards [eg, ICU]) 
• Need for mechanical ventilator support and duration of mechanical ventilator support 
(total days) 
• Need for supplemental oxygen to maintain SpO2 >90% and duration of supplemental 
oxygen (total days) 


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9.9 
Other Assessments and Procedures  
9.9.1 
Informed Consent  
Participants or their legally authorized representative must be consented per the informed 
consent process outlined in Appendix 2. 
9.9.2 
Demographics  
Demographic information, including age, gender, race, and ethnicity, will be obtained if allowed 
per country-specific regulations. 
9.9.3 
Inclusion and Exclusion Criteria  
All inclusion (Section 6.1) and exclusion (Section 0) criteria will be reviewed by the Investigator 
or designee to ensure the participant is eligible for study participation. 
9.9.4 
Medical History  
Medical history will include diagnosis of underlying disease requiring HCT, underlying disease 
state at the time of AdV diagnosis, type of donor and cell source of the transplant received, date 
of HCT, conditioning regimen, CMV serostatus, presence of GVHD, pulmonary function tests, 
and smoking status. 
9.9.5 
SARS-CoV-2 Virus Assessment  
A mid-turbinate nasal swab will be taken to test for SARS-CoV-2 virus by PCR. 
9.9.6 
Randomization  
Patients who meet all of the inclusion criteria and none of the exclusion criteria will be 
randomized in a 
 
 
 
 
 


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10 
STATISTICAL CONSIDERATIONS  
10.1 
Sample Size Determination  
The required sample size is 82 participants  based on the below specifications that have received 
at least 1 dose of posoleucel or PBO.  
The sample size was determined based on the following specifications: 
1. Superiority study comparing posoleucel plus SoC to placebo plus SoC 
2. Primary endpoint is success or failure based on clearance of ADV viremia at Day 29 of 
the Primary Study Period 
3. Allocation (posoleucel:placebo) is 
 
4. Chi-square test  
5. Two-sided alpha = 0.05 
6. True success rate (defined as clearance of virus) for posoleucel = 0.55 
7. True success rate (defined as clearance of virus) for placebo = 0.25 
8. Power = 80% 
A SSRE and futility analysis will be performed after approximately 40 participants have completed 
Day 29 of the Primary Study Period. Details of the SSRE and futility analysis will be provided in 
the SSRE Plan prior to conducting the interim analyses.  
10.2 
Populations for Analyses  
For purposes of analysis, the following populations are defined: 
Population 
Description 
Intent-to-Treat 
(ITT) 
All randomized participants. Participants will be analyzed according to the 
randomized study treatment.  
Modified ITT 
All randomized participants who receive at least one dose of posoleucel or 
placebo. All efficacy endpoints will be analyzed based on the mITT 
Population and these analyses will be considered the primary analyses of 
efficacy. Participants will be analyzed according to the randomized study 
treatment. 
Per Protocol 
(PP) 
All ITT participants who receive any amount of posoleucel or placebo and 
who do not have any major protocol deviations deemed potentially to 
impact efficacy or its evaluation, as defined in the SAP. All efficacy 
endpoints will also be analyzed based on the PP Population, and these 
analyses will be considered secondary analyses of efficacy. Participants 
will be analyzed according to the randomized study treatment.  
Safety 
All participants who receive any amount of posoleucel or placebo and have 
at least 1 post-treatment safety assessment. All safety analyses will be 
based on the Safety Population. Participants will be analyzed according to 
the actual study treatment received.  
 


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10.3 
Statistical Analyses  
The SAP will be developed and finalized before database lock and will describe in detail the 
planned statistical analyses and the procedures for handling missing data. This section is a 
summary of the planned statistical analyses. A separate SSRE Plan will be developed and 
finalized before conducting the interim analysis. 
Summary statistics will be presented by treatment group for the Primary Study Period and by 
cross-over group (Posoleucel/Placebo or Placebo/Posoleucel) based on the treatments received 
for the Cross-Over Period. Unless otherwise stated, continuous variables will be summarized 
using the number of non-missing observations, 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. 
10.3.1 
Efficacy Analyses  
All efficacy endpoints will be analyzed and formally compared between randomized treatment 
groups using statistical tests based on data from the Primary Study Period. In addition, for 
purposes of complete reporting, results for these endpoints will be reported, if appropriate, for 
data from the Cross-Over Period by treatment received in the Cross-Over Period, but no formal 
comparisons or statistical tests will be made. 
The primary and key secondary efficacy endpoints will be analyzed under the estimand 
framework. The estimand attributes will be described in detail in the SAP.  
In order to control the overall type 1 error rate, a sequential approach will be used to analyze the 
primary and key secondary efficacy endpoints, with undetectable viremia (less than LLOQ) at 
Day 29 of the Primary Study Period as the primary efficacy endpoint, followed by progression 
from viremia to target organ disease (for participants without target organ disease at screening), 
progression of target organ disease (for participants with target organ disease at screening), or 
non-relapse mortality during the study as the key secondary efficacy endpoint. 
For AdV viral endpoints at Day 29 or Week 4 visit, a 14-day window will be applied to the Day 
29 visit. The last observed plasma AdV DNA result through Day 29 + 14 days (up to 43 days 
post first infusion) will be used for the analysis. Participants who cross over on or before Day 29 
will be treated as failure.   
All efficacy endpoints will be analyzed based on the mITT Population, and these analyses will be 
considered the primary analyses of efficacy. The primary and key secondary  efficacy endpoints 
will also be analyzed based on the ITT and PP Population to assess the robustness of the primary 
analysis results. 
10.3.1.1 
Primary Efficacy Endpoint Analysis  
The primary efficacy endpoint, undetectable viremia (less than LLOQ) at Day 29 of the Primary 
Study Period, will be summarized by treatment group using the count and percentage, together 
with an exact (Clopper-Pearson) 95% confidence interval for the true percentage.  
The null hypothesis is that the true percentage for posoleucel plus SoC is less than or equal to the 
true percentage for placebo plus SoC, and the alternative hypothesis is that it is greater. This 
endpoint will be analyzed using logistic regression. The model will include a term for treatment 
and the following covariates: level of viremia at Baseline (≥10,000 copies/mL or <10,000 


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copies/mL AdV DNA), age (≥12 years or <12 years) and absolute lymphocyte count at Baseline. 
The null hypothesis will be tested using a one-sided test of the effect of treatment at the 0.025 
significance level. Missing data imputation will be described in the SAP. 
10.3.1.2 
Key Secondary Efficacy Endpoint Analysis  
The key secondary efficacy endpoint will be tested sequentially after the primary endpoint 
reaches statistical significance. The key secondary efficacy endpoint, progression from viremia 
to target organ disease (for participants without target organ disease at screening), progression of 
target organ disease (for participants with target organ disease at screening), or non-relapse 
mortality during the study, will be analyzed in the same manner as the primary efficacy endpoint.  
10.3.1.3 
Other Secondary Efficacy Endpoint Analyses  
Following the key secondary analysis, progression from viremia to target organ disease and 
progression of target organ disease will be analyzed as separate subgroups in a step-down 
manner. If any participants cross over prior to Day 29, they will be considered as having had 
progression, because the necessary condition for cross-over is that the participant progressed to 
active target organ disease (for participants without target organ disease at screening) or 
experienced progression of target organ disease (for participants with target organ disease at 
screening).  
The AAUC for plasma AdV viremia (log10 copies/mL AdV DNA), as assayed by qPCR, through 
Day 29 of the Primary Study Period will be summarized by treatment group using descriptive 
statistics (number of non-missing observations, mean, median, standard deviation, minimum, and 
maximum). The null hypothesis for this endpoint is that the true mean for posoleucel is greater 
than or equal to the true mean for placebo, and the alternative hypothesis is that it is less. The 
null hypothesis will be tested using a one-sided, two-sample t-test with a 0.025 significance 
level.  
The following secondary efficacy endpoints will each be analyzed in the same manner as the 
primary efficacy endpoint: achieving AdV viremia <400 copies/mL AdV DNA at Day 29 of the 
Primary Study Period and AdV disease recurrence during the study among participants who had 
clearance of AdV viremia (prior to any cross-over).  
The Kaplan-Meier estimated median time to resolution of AdV viremia will be presented for 
each treatment group, together with the 95% confidence interval for the true median. The number 
and percentage of censored and uncensored participants will be presented by treatment group. 
The null hypothesis for this endpoint is that the true distributions of time to resolution of AdV 
viremia are equal for posoleucel and placebo, and the alternative hypothesis is that the true 
distributions are different, with the time to resolution of AdV viremia being less for posoleucel. 
The null hypothesis will be tested using a one-sided log-rank test with a 0.025 significance level. 
10.3.1.4 
Cross-Over Analyses  
Undetectable viremia (less than LLOQ) at Day 29’ of the Cross-Over Period will be summarized 
by cross-over group using counts and percentages, together with exact (Clopper-Pearson) 95% 
confidence intervals for the true percentages. Achieving AdV viremia <400 copies/mL AdV 
DNA at Day 29’ of the Cross-Over Period and AdV disease recurrence during the 24-week 
Cross-Over Period among participants who had clearance of AdV viremia (after cross-over) will 
be analyzed in the same way.  


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The AAUC for plasma AdV viremia (log10 copies/mL AdV DNA), as assayed by qPCR, through 
Week 24’ of the Cross-Over Period will be summarized by cross-over group using descriptive 
statistics. 
The Kaplan-Meier estimated median time to resolution of AdV viremia will be presented for 
each cross-over group, together with the 95% confidence interval for the true median. Cross-over 
participants who do not achieve resolution of AdV viremia will be censored as of their last study 
visit. The number and percentage of censored and uncensored participants will be presented by 
cross-over group. 
Progression from viremia to target organ disease (for participants without target organ disease at 
screening, progression of target organ disease (for participants with target organ disease at 
screening), or non-relapse mortality during the 24-week Cross-Over Period will not be analyzed, 
because all cross-over participants must have already progressed to target organ disease prior to 
being crossed over.  
10.3.2 
Analysis of Safety  
Safety will be analyzed and compared between treatment received based on data from the 
Primary Study Period. In addition, for purposes of complete reporting, safety will be reported for 
data from the Cross-Over Period by treatment received in the Cross-Over Period, but no 
comparisons will be made between the two treatments. 
The primary safety endpoint is the incidence and severity of TEAEs, including individual AESIs, 
during the study. The safety profile will be further assessed based on changes in clinical 
laboratory assessments, vital signs, ECGs, and physical examinations. All safety analyses will be 
based on the Safety Population. 
Safety analyses in general will be descriptive and will be presented by study period (Primary 
Study Period or Cross-Over Period) and treatment group or cross-over group in a tabular format. 
Categorical endpoints will be summarized using number and percentage of participants within 
each category. Continuous endpoints will be summarized descriptively with summary statistics 
(number of non-missing observations, mean, standard deviation, median, minimum, and 
maximum). 
A TEAE is defined as an adverse event with a start date and time on or after the administration 
of investigational product or placebo or that worsened in severity after administration of 
investigational product or placebo through the end of the study. For AEs with a missing start 
date, the AE will be considered treatment-emergent unless there is additional information 
indicating that the AE started prior to study treatment. The number and percentage of 
participants with TEAEs will be tabulated by Medical Dictionary for Regulatory Activities 
(MedDRA) System Organ Class and Preferred Term for each treatment group/cross-over group. 
This will be done overall, by severity, and by relationship to treatment. Adverse events leading to 
discontinuation of the study, SAEs, and AESIs will be summarized by treatment group. By-
participant listings will also be provided for any deaths, SAEs, AESIs, and adverse events 
leading to discontinuation of study drug. 
The incidence and severity of acute GVHD during the study, the incidence and severity of 
chronic GVHD during the study, the incidence and severity of CRS during the study, and the 
incidence and severity of any treatment-emergent AESIs during the study will each be 


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summarized by treatment group for the Primary Study Period and by cross-over group for the 
Cross-Over Period using counts and percentages. 
Clinical laboratory data will be summarized by laboratory test, visit, and treatment group using 
descriptive statistics. The changes from baseline to each post-baseline visit will also be 
summarized.   
Vital signs data will be summarized by visit and treatment group for each vital sign using 
descriptive statistics. The changes from baseline to each post-baseline visit will also be 
summarized.   
ECG data will be summarized by visit and treatment group for each quantitative ECG parameter 
using descriptive statistics. The changes from baseline to each post-baseline visit will also be 
summarized.   
Abnormal physical examination findings will be presented in a by-participant data listing.  
10.3.1 
Interim Analyses  
A sample size re-estimation (SSRE) and a futility analysis will be performed after approximately 
40 participants have completed Day 29 of the Primary Study Period. The SSRE will be based on 
the conditional power (CP), ie, the conditional probability of rejecting the null hypothesis, using 
the method of Mehta and Pocock (2010) for a CP of 80%. For the futility analysis, a CP cutoff of 
10% will be applied. The interim analyses (SSRE and futility analysis) will both be conducted in 
a manner so as to minimize the risk of operational bias. It will be done under the auspices of the 
independent DSMB overseeing the study. The analyses will be performed by an independent 
statistician. The unblinded data generated and discussed by the DSMB for the interim analyses 
will be kept confidential. In particular, the information will not be accessible to the investigators 
and site staff, the Sponsor’s team and medical monitor, and CRO blinded team members, or the 
Adjudication Committee. 
 
 


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REFERENCES  
Al-Akioui-Sanz K, Pascual-Miguel B, et al. Donor selection for adoptive cell therapy with 
CD45RA memory T cells for patients with coronavirus disease 2019, and dexamethasone and 
interleukin-15 effects on the phenotype, proliferation and interferon gamma release. 
Cytotherapy. 2023 Mar;25(3):330-340. doi:10.1016/j.jcyt.2022.12.001 
Feghoul L, Chevret S, Cuinet A, et al. Adenovirus infection and disease in paediatric 
haematopoietic stem cell transplant patients: clues for antiviral pre-emptive treatment. Clin 
Microbiol Infect. 2015;21(7):701-709. doi:10.1016/j.cmi.2015.03.011 
Hiwarker P, Kosulin K, Cesaro S, et al. Management of adenovirus infection in patients after 
haematopoietic stem cell transplantation: state-of-the-art and real-life current approach: a 
position statement on behalf of the Infectious Diseases Working Party of the European Society of 
Blood and Marrow Transplantation. Rev Med Virol. 2018;28(3):e1980. 
Matthes-Martin S, Feuchtinger T, Shaw PJ, et al. European guidelines for diagnosis and 
treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL-4 
(2011). Transpl Infect Dis. 2012;14(6):555-563. 
Mynarek M, Ganzenmueller T, Mueller-Heine A, et al. Patient, virus, and treatment-related risk 
factors in pediatric adenovirus infection after stem cell transplantation: results of a routine 
monitoring program. Biol Blood Marrow Transplant. 2014;20(2):250-256. 
Sedláček P, Petterson T, Robin M, et al. Incidence of adenovirus infection in hematopoietic stem 
cell transplantation recipients: findings from the AdVance Study. Biol Blood Marrow Transplant. 
2019;25(4):810-8. 
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/wpcontent/uploads/2018/03/EBMT2018_Zecca-et-al_AdVance-AdV-
Outcomes-Presentation.pdf. Accessed 09 Nov 2020. 
Zecca M, Wynn R, Dalle JH, et al. Association between adenovirus viral load and mortality in 
pediatric allo-HCT recipients: the multinational AdVance study. Bone Marrow Transplant. 
2019;54(10):1632-1642.  
Mehta CR, Pocock SJ. Adaptive increase in sample size when interim results are promising:  
A practical guide with examples. Statistics in Medicine 2011; 30:3267-3284. 
 
 


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12 
APPENDICES  
 


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APPENDIX 1: ABBREVIATIONS  
Abbreviation 
Definition 
AAUC 
time-averaged area under the concentration-time curve 
AdV 
Adenovirus 
AE 
adverse event 
AESI 
adverse event of special interest 
allo-HCT 
allogeneic hematopoietic stem cell transplant 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATG 
anti-thymocyte globulin 
BAL 
bronchoalveolar lavage 
BKV 
 
BK virus 
BSA 
body surface area 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CIBMTR 
Center for International Blood and Marrow Transplant Research 
CMV 
Cytomegalovirus 
COA 
clinical outcome assessment 
COVID-19 
coronavirus disease 2019 
CP 
conditional power 
CR 
complete response 
CRA 
Clinical Research Associate 
CRS 
cytokine release syndrome 
CSF 
cerebrospinal fluid 
CT 
computed tomography 
CTA 
Clinical Trial Authorisation 
DNA 
deoxyribonucleic acid 
DRE 
disease-related event 
DSMB 
Data and Safety Monitoring Board 
EBV 
Epstein-Barr virus 
ECG 
Electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EQ-5D 
European Quality of Life 5 dimensions 
EQ-5D-5L 
5-level European Quality of Life 5 dimensions 
EQ-5D-Y 
European Quality of Life 5 dimensions Youth 
EQ VAS 
European Quality of Life Visual Analog Scale 
ET 
Early Termination 


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Abbreviation 
Definition 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume in the first second 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
GVHD 
graft versus host disease 
HCT 
hematopoietic stem cell transplant 
HHV-6 
human herpesvirus 6 
HLA 
human leukocyte antigen 
HRT 
hormone replacement therapy  
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
ICU 
intensive care unit 
I/E 
inclusion and exclusion 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Committee 
IRR 
infusion-related reaction 
IRT 
interactive response technology 
ITT 
Intent-to-Treat 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
IV 
intravenous(ly) 
JCV 
John Cunningham virus 
LFT 
liver function test 
LLOQ 
lower limit of quantitation 
MAGIC 
Mount Sinai Acute GVHD International Consortium 
MedDRA 
Medical Dictionary for Regulatory Activities 
NA 
not applicable 
NR 
no response 
PBMC 
peripheral blood mononuclear cell 
PP 
Per Protocol 
PR 
partial response 
qPCR 
quantitative polymerase chain reaction 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SoA 
Schedule of Activities 
SoC 
standard of care 
SpO2 
peripheral capillary oxygen saturation 


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Abbreviation 
Definition 
SSRE 
sample size re-estimation 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
US 
United States 
VST 
virus-specific T cell 
WBC 
white blood cell 
WOCBP 
woman/women of childbearing potential 
 
 


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APPENDIX 2: STUDY GOVERNANCE CONSIDERATIONS  
Regulatory and Ethical Considerations 
Ethical Conduct of the Study 
This study will be conducted in accordance with the protocol and with the consensus ethical 
principles derived from international guidelines, including the Declaration of Helsinki and 
Council for International Organizations of Medical Sciences International Ethical Guidelines, 
applicable International Council for Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines, and all applicable laws and regulations. 
Institutional Review Board/Independent Ethics Committee 
Institutional Review Board 
The IRB will review all appropriate study documentation in order to safeguard the rights, safety, 
and well-being of patients. 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 patients, safety updates, annual progress reports, and any revisions to these documents will 
be provided to the IRB by the Investigator.  
No drug will be released to the site for dosing until written IRB authorization has been received 
by the Sponsor. 
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. 
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 patient 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 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 Clinical Research Associate (CRA) will review the data for safety 
information, completeness, accuracy, and logical consistency. Computer programs that identify 


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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. 
Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by Medpace or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol, and protocol amendments will be submitted to regulatory authorities and ethics 
committees/IRBs as appropriate. A protocol amendment may be implemented after it has been 
approved by the IRB, unless immediate implementation of the change is necessary for patient 
safety. In this case, the situation must be documented and reported to the IRB within 5 working 
days. 
 
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. 
 
Informed Consent Process 
Informed Consent 
Prior to conducting any study-related activities, written informed consent to participate in the 
study must be provided by the patient, or a parent or legal guardian must provide written 
informed consent and the potential pediatric patient must provide assent in a manner approved by 
the IRB/IEC and local regulations. In some jurisdictions, legally effective informed consent must 
be obtained from all legal guardians for minor patients.  
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 prior to its use and 
must be in compliance with all ICH GCP, local regulatory requirements, and legal requirements.  
The Investigator must ensure that each study patient is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
patient has been informed of his/her rights to privacy. The Investigator will obtain written 
informed consent from each patient, or the patient’s parent/legal guardian and assent from the 
potential pediatric patient, 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 patient and his/her 
parent/legal guardian when applicable. 


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Subject Card 
On enrollment in the study, the patient will receive a subject card to be carried at all times. The 
subject card will state that the patient is participating in a clinical research study, type of 
treatment, and contact details in case of an SAE. 
 
Data Protection 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names or 
any information which would make the participant identifiable will not be transferred.  
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
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. 
 
Committees Structure 
Independent DSMB and Adjudication Committees will be convened for this study to routinely 
monitor patient safety and evaluate prespecified interim analyses for futility and sample size re-
estimation. 
Data and Safety Monitoring Board 
The DSMB will receive summary reports of all unexpected SAEs at least monthly. A DSMB 
charter, detailing all aspects of the DSMB’s composition, scope of review, and procedures will 
be provided separately. 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. 
Adjudication Committee 
The Adjudication Committee will be independent, and all members will remain blinded to the 
randomized treatment arm. The Adjudication Committee will adjudicate adenovirus target organ 
disease at Day 29 (Appendix 8). More details are provided in a separate Adjudication Committee 
charter.  
 


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Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. Each 
Investigator is obligated to keep data pertaining to the study confidential. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
 
Dissemination of Clinical Study Data 
Study-related information and study results may be posted on publicly accessible clinical study 
databases (eg, the US website www.clinicaltrials.gov or the EU website 
www.clinicaltrialsregister.eu), as appropriate, and in accordance with national, regional, and 
local regulations. 
 
Data Quality Assurance 
Data Handling 
Data will be recorded at the sites on eCRFs and reviewed by the CRA during monitoring visits. 
The CRAs will verify data recorded in the electronic data capture (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. 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory 
requirements. 
Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure user name 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. 
Medical Information Coding 
For medical information, the following thesauri will be used: 
• MedDRA (latest) for medical history and adverse events 
• World Health Organization Drug Dictionary for prior and concomitant medications 


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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. 
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 participating patients (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.  
 
Source Documents 
Records of patients, 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. 
 
Study and Site Closure 
The Sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at its sole discretion. 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: 


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• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study treatment development 
 
Insurance and Indemnity 
In accordance with the relevant national regulations, the Sponsor will take out patient liability 
insurance for all patients who give their consent to the clinical study. This cover is designed for 
the event that a fatality, physical injury, or damage to health occurs during the clinical study’s 
execution. 
 
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 Ethics 
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• Microscopy [2] 
• AdV viral load [3] 
Viral Load in Blood 
(Central 
Laboratory) 
AdV [4] 
BKV 
CMV 
EBV 
HHV-6 
JCV 
Viral Load in Stool 
(Central 
Laboratory) 
AdV 
Viral Load from 
Nasopharyngeal 
Swab (Central 
Laboratory) 
AdV 
Viral Load from 
BAL (Central 
Laboratory) [5] 
AdV 
Viral Load from 
CSF (Central 
Laboratory) [6] 
AdV 
Other Laboratory 
Assessments 
• SARS-CoV-2 PCR virus assessment (mid-turbinate nasal swab) 
• FSH [7] 
• Serum pregnancy test [8] 
• Urine pregnancy test [8] 
• PBMCs and plasma [9] 
1. Manual microscopic review of peripheral blood smears is performed only if WBC count and/or differential 
values are out of reference range. 
2. Urine microscopy is always performed (cannot be replaced with a dipstick analysis). 
3. While not a routine evaluation in this study, any participants who manifest clinical signs and/or symptoms of 
AdV hemorrhagic cystitis should have a urine sample sent to the central laboratory for determination of AdV 
viral load. For this subset of participants, AdV urine viral loads should be measured weekly at the central 
laboratory until resolution of hemorrhagic cystitis. 
4. Since AdV infections may progress rapidly, participants may be randomized and dosed (with Medical 
Monitor approval) based on local laboratory AdV viremia results if the central laboratory screening viremia 
result is not yet available at the time of intended dosing. 
5. For participants who require intubation and/or undergo bronchoscopy with BAL, the BAL fluid will be 
obtained for AdV viral load determination at the central laboratory. 
6. For participants who develop symptoms and/or signs of possible AdV-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 AdV viral load determination should, when possible, be sent 
to the central laboratory. 
7. 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. 
8. For female participants of childbearing potential only. A serum (human chorionic gonadotropin) pregnancy 
test will be performed at screening. Serum or urine pregnancy testing will be performed at other time points 
as indicated in Section 2. 
9. At each time point indicated in Section 2, blood will be collected into a cell separation tube and processed to 
generate a PBMC fraction and a plasma fraction. Genomic DNA will be extracted from the PBMC fraction. 


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The genomic 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). 
AdV = adenovirus; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BAL = bronchoalveolar 
lavage; BKV = BK virus; BUN = blood urea nitrogen; CMV = cytomegalovirus; CSF = cerebrospinal fluid; 
EBV = Epstein-Barr virus; FSH = follicle-stimulating hormone; HHV-6 = human herpesvirus 6; JCV = John 
Cunningham virus; PBMC = peripheral blood mononuclear cell; RBC = red blood cell; WBC = white blood cell. 
 
Investigators must document their review of each laboratory safety report. 
Study blood sampling volumes and sampling schedule by body weight are described in the 
Laboratory Manual. 
 














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• 
If the event meets serious criteria and it is not possible to access the EDC system, send an 
email to 
 at 
 or fax/email the 
completed paper SAE form to 
 (contact information listed in Section 9.2.6.1) 
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. 
• 
Initial notification via telephone does not replace the need for the Investigator to complete 
and sign the SAE data collection tool within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in Section 9.2.6.1. 
 
 
 


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APPENDIX 5: CONTRACEPTIVE GUIDANCE AND COLLECTION OF 
PREGNANCY INFORMATION  
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high FSH level in the postmenopausal range may be used to confirm 
a postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, a 
single FSH measurement is insufficient.  
• Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception Guidance 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% per year 
when used consistently and correctly. 
• Implantable progestogen-only hormone contraception associated within inhibition of 
ovulationc 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS)c 
• Bilateral tubal occlusion 
• Azoospermic partner (vasectomized or due to a medical cause) 


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Azoospermia is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the woman of childbearing potential and the absence of sperm has 
been confirmed. If not, an additional highly effective method of contraception should be 
used. Spermatogenesis cycle is approximately 90 days. 
Note: documentation of azoospermia for a male patient can come from the site personnel’s 
review of the patient’s medical records, medical examination, or medical history interview. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year when 
used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
- 
oral 
- 
intravaginal 
- 
transdermal 
- 
injectable 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
- 
oral 
- 
injectable 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the patient. 
Effective Methodsd That Are Not Considered Highly Effective Failure rate of ≥1% per 
year when used consistently and correctly. 
• Progestogen-only oral hormonal contraception where inhibition of ovulation is not the 
primary mode of action. 
• Male or female condom with or without spermicide 
• Cervical cap, diaphragm, or sponge with spermicide 
• A combination of male condom with either cervical cap, diaphragm, or sponge with 
spermicide (double-barrier methods)e 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c. 
If locally required, in accordance with Clinical Trial Facilitation Group guidelines, acceptable contraceptive 
methods are limited to those which inhibit ovulation as the primary mode of action. 
d. Considered effective, but not highly effective - failure rate of ≥1% per year. Periodic abstinence (calendar, 
symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational 
amenorrhea method are not acceptable methods of contraception. 
e. Male condom and female condom should not be used together (due to risk of failure from friction). 


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APPENDIX 6: 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). 
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 patients with acute 
GVHD. 2009. https://www.cibmtr.org/Meetings/Materials/GVHDworkshop/pages/index.aspx. Accessed 13 May 2019. 
 
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 
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). 
FEV1 = forced expiratory volume in the first second; 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 7:  CYTOKINE RELEASE SYNDROME SCALE  
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 principle factor leading to the outcome. 
a. Fever is defined as temperature 38.0C not attributable to any other cause. In patients 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 
patient 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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Adenovirus 
hepatitis  
• AdV identified via hepatic biopsy via antigen/IHC, 
or culture  
OR  
• AdV viremia/DNAemia (defined above)   
AND  
• Evidence of new or worsening transaminitis, 
defined as meeting the below criteria or if already 
met, then an increase by at least 100 IU/mL:  
o ALT >5xULN   
o AST >5xULN  
  
Available alternative etiology assessment results, 
both infectious (e.g. hepatitis viral tests) and non-
infectious (e.g. drug-induced-liver injury, GvHD) will 
be provided to the CAC.  
• Deteriorating liver function without alternative 
attribution:  
o Progression of transaminases   
o AST/ALT increase by >2-3X from baseline for 
progression of hepatitis  
o Decreasing AST/ALT with increasing bili and 
worsening synthetic function (>30% from 
baseline) – for burnt-out hepatitis  
o Progression of hyperbilirubinemia  
▪ >30% increase in dBili from baseline  
o Worsening of hepatic synthetic activity (e.g., 
PTT, pre-albumin, ammonia/lactate other)  
▪ >30% worsening from baseline  
o Development of clinical signs of hepatic 
decompensation  
Adenovirus 
enterocolitis  
• AdV detected on bowel biopsy via antigen/IHC 
and/or culture/PCR   
AND    
• Both of the following:  
o Suggestive signs or symptoms (e.g., 
diarrhea, abdominal pain, ileus, vomiting, GI 
bleeding)   
AND  
o Endoscopic evidence of lesions 
(macroscopic or microscopic) not attributed 
to GVHD (or other non-ADV effect) OR 
cytopathic adenoviral effect identified on 
biopsy  
OR  
• At least two suggestive signs or symptoms: 
diarrhea, abdominal pain, ileus, vomiting, GI 
bleeding   
AND  
• AdV isolated from the stool by culture or PCR    
  
Available alternative etiology assessment results 
(e.g., bacterial, viral, amebic, GVHD) will be 
provided to the CAC.    
• Worsening clinical signs or symptoms 
(better/worse/same) without alternative 
attribution:   
o diarrhea  
o abdominal pain  
o ileus, vomiting  
o GI hemorrhage  
AND  
• AdV in stool persistently positive (qualitative)  
  
Available alternative etiology assessment results 
(e.g. GI GVHD) will be provided to the CAC.    
 
Adenovirus 
pancreatitis  
• AdV identified by pancreatic biopsy or ERCP 
brushings/washings via antigen/IHC or culture   
AND  
• At least two clinical and imaging findings such 
as:  
o Suggestive signs or symptoms (abdominal 
pain, GI symptoms)   
o Amylase or lipase >5xULN  
o Imaging (e.g., CT scan) findings suggesting 
pancreatitis  
  
• Progression of clinical and/or imaging findings 
such as:  
o Suggestive signs or symptoms (abdominal 
pain, GI symptoms)  
o Amylase or lipase   
o Worsening systemic disease (DIC, sepsis, 
hemodynamic instability)  
o Imaging (eg, CT scan) findings suggesting 
progressive pancreatitis  


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Adenovirus 
hemorrhagic cystitis  
• Clinical symptoms of cystitis, including dysuria, 
lower abdominal pain, and/or other bladder-
associated pain or spasms   
AND  
• Grade ≥2 hematuria (per Bedi scale)  
AND  
• Documented AdV viruria  
Available alternative etiology assessment results 
(e.g. BK virus) will be provided to the CAC.  
• Worsening disease based on ≥1 grade increase 
in Bedi scale  
o E.g., Macroscopic hematuria to clots (Gr 2 to 
3) ; or clots to renal insufficiency (Gr 3 to 4)  
• Requirement for surgical intervention (e.g., 
nephrostomy tubes, cystectomy, arterial 
embolization)  
• Persistent AdV viruria  
Adenovirus 
nephritis  
• Suggestive signs or symptoms of nephritis 
(impaired renal function, proteinuria, microscopic 
hematuria, hypertension, flank pain)  
OR  
• Enlarged kidney on imaging   
OR  
• Renal obstruction  
AND  
• One of the following:  
o AdV identified via renal biopsy via 
antigen/IHC or culture   
OR  
o AdV viruria   
OR   
o If both AdV viruria and renal biopsy results 
are not available, then AdV viremia/DNAemia 
(defined above) may be considered.  
Available alternative etiology assessment results 
(e.g. BK virus, JC virus, bacterial and drug-induced) 
will be provided to the CAC.   
• Worsening of clinical signs/symptoms:  
o Impaired renal function   
o Proteinuria   
o Microscopic hematuria   
o Hypertension   
o Flank pain   
Adenovirus 
encephalitis/myelitis  
• At least one of the following signs/symptoms of 
encephalitis:  
o Abnormal CSF  
o Focal CNS deficit  
o Cognitive impairment  
o Visual symptoms  
o Seizure   
o Evidence of compatible lesions by CT scan 
or MRI   
AND  
• AdV identified in CSF via antigen/IHC, culture, 
PCR, or histopath from brain biopsy   
OR (if not possible to perform a lumbar puncture):  
• At least two of the following signs/symptoms of 
encephalitis:  
o Focal CNS deficit  
o Cognitive impairment  
o Visual symptoms  
o Seizure   
o Evidence of lesions by CT scan or MRI   
• Worsening signs/symptoms of encephalitis:  
o Worsening CSF findings  
o Increase in number/severity of focal CNS 
deficits  
o Worsening cognitive impairment   
o Worsening visual symptoms   
o New onset seizure, or worsening of existing 
seizures   


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AND  
• AdV viremia/DNAemia (defined above)  
Available alternative etiology assessment results 
(e.g. JC virus, bacterial, amebic infections and 
stroke/infarct/CSF leak) will be provided to the CAC. 
Adenovirus 
retinitis/ocular 
disease  
• Ophthalmologic exam demonstrating findings 
consistent with retinitis/ocular disease (e.g., 
retinitis, keratitis, keratoconjunctivitis sicca, 
iridocyclitis, retinopathy, visual field defects, 
papilledema, diplopia) and other possible causes 
(e.g., HIV, CMV, fungal, mycobacterial, bacterial 
infection, and/or neurologic etiology) not 
considered more likely as the only cause   
AND  
• Detection of AdV by PCR from the aqueous or 
conjunctiva   
• Clinical assessment (by ophthalmologist) of 
progressive ocular disease  
Adenovirus carditis  • Specimen from cardiac source (e.g., cardiac 
tissue biopsy, pericardial fluid) positive for AdV 
plus evidence of carditis, myocarditis, or 
pericarditis (e.g., ECHO findings or drained fluid 
reveals evidence of inflammation) WITHOUT 
microbiologic evidence of another infectious 
pathogen or evidence of concurrent GVHD at any 
site that could explain the presentation.   
• Worsening heart failure/ejection fraction on 
Echocardiography OR  
• New requirement for ECMO  
Death attributable to 
AdV disease  
• Proven: Autopsy with histopathologic evidence 
for human adenovirus presence associated with 
tissue destruction regardless of other etiologies 
for death.   
• Probable: Previously met criteria for probable or 
proven adenovirus-related disease within the 
preceding 8 weeks without resolution of 
symptoms consistent with adenovirus-associated 
disease and without other clear etiology for death 
and with no autopsy available  
• Not applicable  


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APPENDIX 9:  ESTIMATING FRACTION OF INSPIRED OXYGEN  
Method 
O2 Flow (L/min) 
Estimated FiO2 (%) 
Nasal cannula 
1 
24 
2 
28 
3 
32 
4 
36 
5 
40 
6 
44 
Nasopharyngeal catheter 
4 
40 
5 
50 
6 
60 
Face mask 
5 
40 
6-7 
50 
7-8 
60 
Face mask with reservoir 
6 
60 
7 
70 
8 
80 
9 
90 
10 
95 
Source: https://www.intensive.org/epic2/Documents/Estimation%20of%20PO2%20and%20FiO2.pdf; accessed 
16 December 2021 
Summary: 
• Nasal cannula oxygen at standard flow rates is acceptable (even at 6 L/min, FiO2 is 
expected to be <50%). 
• Standard face mask oxygen is acceptable at flow rates <7 L/min. 
• Face mask with reservoir is not acceptable since FiO2 is expected to exceed 50% at all 
flow rates. 
• Nasopharyngeal catheters at flow rates <5 L/min are acceptable. 


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APPENDIX 10:  AMENDMENT CHANGES AND RATIONALE  
Amendment history is provided below. 
Protocol Version 
Date 
Patient Enrollment 
Original, Version 1 
20 August 2021 
Yes 
Amendment 1, Version 2.0 
17 December 2021 
None 
Amendment 2, Version 3.0 
23 August 2022 
Yes 
Amendment 3, Version 4.0 
15 September 2023 
Not Used 
Amendment 3, Version 4.0 
21 September 2023 
Yes 
Amendment 4, Version 5.0 
30 November 2023 
None 
 
Amendment 4 Rationale 
Major Revisions include: 
• Addition of Interim analysis (sample size re-estimation and futility analysis) 
Rationale: AlloVir has decided to add back in the interim analysis for a sample size re-
estimation and futility analysis that were originally planned to address the lack of adequate 
published data on the natural history of AdV infection in a similar patient population as those 
enrolled into the AdV Ph3 study. The SSRE/futility assessment will provide an opportunity 
to increase the sample size and the study power to detect a treatment response based on the 
interim data. 
• Changes in Sample Size Determination  
Rationale: The assumptions in sample size determination were updated to be more 
conservative. The method of the sample size calculation is changed to a Chi-square test 
because the sample size is sufficient to use this method and it is consistent with the test used 
for logistic regression model of the primary analysis. Patients who drop out will be included 
in the analysis, therefore, the dropout rate is not considered in the calculation. 
• Changes in Primary Analysis  
Rationale: Based on published data absolute lymphocyte count is believed to be a strong 
predictor of clinical outcome, therefore it has been included as a covariate in the model for 
post-randomization adjustment. 
Amendment 3 Rationale 
There is a significant unmet medical need for an AdV treatment option in immunocompromised 
allo-HCT patients. The population of allo-HCT patients that develop clinically significant AdV 
infection, as defined by the AdV viral load eligibility criteria, post allo-HCT is limited. However, 
those that do reactivate or develop de novo AdV infection can rapidly progress to severe disease 
leading to an increase rate of mortality. Given the limited population of allo-HCT that develop 


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clinically significant AdV infection, enrollment into this trial is approximately 2-3 patients per 
month.  
The purpose of this amendment was to broaden eligibility criteria and modify study conduct to 
support acceleration of enrollment. Additional changes were made to correct errors and to 
provide additional clarity and consistency. 
Major Revisions include: 
• Revised Eligibility Criteria 
Revised Inclusion Criteria #1 to allow enrollment of patients <1 year of age. 
Rationale: DSMB has reviewed the safety data for patients between 1 and <6 years old and 
approved enrollment of patients under 1.  
Revised Exclusion Criteria # 2 to allow patients actively undergoing corticosteroid tapering 
to prednisone equivalent dose of 0.5 mg/kg/day to be dosed once they have reached ≤ 1 
mg/kg/day with Medical Monitor approval, with the expectation that the corticosteroid taper 
will continue. 
Rationale: AdV infections in immunocompromised HCT recipients can progress rapidly. 
Post allo-HCT, patients may be on high dose systemic steroids for prophylaxis of GvHD 
which would take time to taper down to 0.5 mg/kg/day. There is new literature support for 
minimal impact of VST function with steroids at typical clinical doses (Al-Akioui-Sanz 
2023). Modifying this criterion would provide patients earlier access to study treatment while 
they continue to taper steroids and minimize risk to efficacy response for dose 2.   
Revised Exclusion Criteria #4 to broaden the treatment population to patients with active 
malignancies that are slow growing and/or stable disease.  
Rationale: The intent was to exclude patients with unstable active malignancies that could 
potentially confound safety in this patient population. However, active malignancies that are 
stable on treatment or slow growing are not likely to confound the safety results collected 
during the 20-week safety follow up period. This change would not impact safety or efficacy 
for patients enrolled in the study.     
• Concomitant Medications: 
Revised medication restriction for cidofovir use to allow sites to use cidofovir at any time 
during the study  
Rationale: Cidofovir is not approved for the treatment of AdV infection and has been shown 
to be associated with an increased risk of nephrotoxicity. The antiviral activity of cidofovir 
and long-term efficacy has not been well studied and is felt to be poor in 
immunocompromised post allo-HCT patients. However, clinicians often administer cidofovir 
to patients with AdV infection because there are no available approved treatment options. 
The modified cidofovir usage language will provide clinical sites the ability to maintain their 
standard practice for initiation and stopping of cidofovir. Given the limited data to support 
efficacious use of cidofovir for AdV infection this change would support a real-world 
evaluation of current standard of care.  


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• Analysis updates: 
Removal of the Interim Analysis 
Rationale: The interim analysis that included an SSRE and futility assessment was removed. 
The study will continue enrollment per the current sample size as planned without an SSRE 
or futility given the slow rate of enrollment of this rare patient population.           
Change from ITT to mITT 
Rationale: The time from randomization to study treatment infusion is typically delayed by 
~5 days due to operational feasibility of shipping HLA matched VST or placebo to the study 
center and scheduling of treatment administration.  This delay has led to a larger than 
expected number of patients that have randomized and not been treated.  Given the smaller 
sample size in this rare patient population study, an ITT analysis that includes randomized 
but not treated patients has the potential to obscure the biological effects of VST versus 
placebo for the primary endpoint. Excluding randomized patients who did not receive at least 
1 infusion of study treatment (ie. modified ITT analysis) is not expected to introduce bias by 
performing the primary analysis on a post-randomization population. The reason patients 
were randomized and not treated was not influenced by treatment assignment as the study is 
blinded. The primary reasons for patient not to receive treatment are withdraw of consent 
from study or new data becoming available after randomization and prior to treatment that 
can lead to removal of the patient from the study, including clearance of AdV viremia. 
Excluding these patients will lead to a more informative analysis focused only on patients 
that received at least 1 dose of study treatment.  
The mITT analysis would better represent the treatment response in real-world clinical 
practice in which patients that clear AdV viremia or decide against treatment would not 
receive VSTs.  The primary efficacy endpoints will also be analyzed based on the ITT 
Population to assess the robustness of the primary analysis results. 
Added analysis window for primary and secondary AdV viral load endpoints 
Rationale: The rationale for selection of Day 29 for the primary and secondary AdV viral 
load endpoints were based on the results from the Phase 2 CHARMS study, reference 
Section 5.4 above. The two AdV assays used in CHARMS had a higher lower limit of 
quantitation (LLOQ) of 172 and 190 copies/mL as compared to the assay used in this Phase 3 
study with an LLOQ of 32 copies/mL. Review of blinded data in patients with declining AdV 
viremia showed a delay in reaching <LLOQ beyond Day 29 in some patients. This window 
would allow the last observed result to be used for primary endpoint analysis when applying 
this more sensitive assay.   
 
• Other changes: 
Modification of criteria for cell line assignment for the second dose (primary study 
period or cross-over) 
Rationale: 


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The current dose 2 criterion is based on an AdV viral load cutoff of 10,000 copies/mL to 
determine if a patient should switch to a second cell line (or placebo). The intent of a cell line 
switch criteria is to provide patients who have little to no response to Dose 1, as determined 
by their AdV viral load on Study Day 8 or Day 11, access to a second cell line (or placebo). 
The second cell line may provide the patient with different HLA matches increasing their 
chance of a treatment response.   
However, the current criteria do not consider the patient’s baseline AdV viral load. Upon 
review of blinded data, patients with high baseline AdV viral loads demonstrate a significant 
decline of over 0.5 log10 copies/mL by Day 8 were switching cell lines (or placebo) at Dose 2 
based on the current switch criteria. Given the initial cell line assigned to each patient is the 
best HLA matched cell line or placebo that is available, patients demonstrating a treatment 
response should maintain their current cell line. 
This change will consider a patient’s baseline AdV viral load when determining treatment 
response and allow patients that demonstrate a significant treatment response as defined by 
AdV viral load decline ≥0.5 log10 copies/mL the ability to stay on the initial cell line 
assigned.  
Section 7.2 Dose Modification 
Modified text and deleted GVHD text referencing treatment discontinuation section.   
Rationale: Text was modified to clarify no dose modifications were allowed in the study. 
Additional GVHD text was deleted, and the appropriate protocol section referenced for 
clarity.  
 
Updated CAC Definitions to reflect the changes as agreed upon by the committee members 
and finalized in the CAC Charter v2.0 17May2023 
Amendment 2 Rationale 
This amendment was made to address issues relating to study conduct that arose from 
investigators and study site personnel after study initiation. Additional changes were made to 
correct errors and to provide additional clarity and consistency. 
Major Revisions include: 
• Revised the order and timing of Study Objectives and Endpoints 
The order of the secondary objectives, relating to the progression to/of target organ 
disease, were switched, as indicated below, to make the assessment “during the study” 
the key secondary objective, and to make assessment “by Day 29” an other secondary 
assessment.  (Sections 1, 4, 10.3.1, and 10.3.1.2). 
Change to the timing of the key secondary objective of “to determine the percent of 
participants who develop target organ AdV disease (eg, lower tract respiratory disease 
documented radiographically, AdV-associated hemorrhagic cystitis, severe hepatitis) or 
whose target organ disease progresses” and its associated endpoint from “by Day 29” to 
“during the study” (Sections 1, 4, 10.3.1, and 10.3.1.2). 


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Changed the timing of the other secondary objective of “to determine the percent of 
participants who develop target organ AdV disease (eg, lower tract respiratory disease 
documented radiographically, AdV-associated hemorrhagic cystitis, severe hepatitis) or 
whose target organ disease progresses” and its associated endpoint from “during the 
study” to “by Day 29” (Sections 1 and 4). 
Rationale: An assessment of disease progression over the entire duration of the study has 
been considered to be more clinically important than an assessment of disease 
progression over the first 29 days of the study. As before, both of these objectives will be 
captured as secondary, the only change is in the ordering of the key secondary objective.   
Moved the secondary endpoints of proportion of participants with undetectable viremia 
(less than LLOQ) at Day 29 in participants without and with AdV disease at screening 
from key secondary endpoints to other secondary endpoints (Sections 1 and 4).  
Rationale: These secondary endpoints are not related to the key secondary endpoint and 
should be included in the other secondary endpoints. Their previous placement under key 
secondary endpoint was a typographical error. 
• Revised Eligibility Criteria  
Updated from Inclusion Criterion #2 to remove the requirement that participants had to 
have an absolute neutrophil count > 500/mm3 at screening and instead allowed absolute 
neutrophil count > 500/mm3 at any time post allogeneic cell transplantation and by 
screening (Sections 1 and 6.1).  
Rationale: Adenovirus infection itself may cause neutropenia in an otherwise engrafted 
HCT recipient, and in these cases, treating the adenovirus infection may be beneficial.  
Added “had a cord blood transplant” to Inclusion Criterion 2b.  
Rationale: Cord blood transplant are considered an independent high-risk criterion for 
progression of AdV infection (Feghoul, 2015; doi: 10.1016/j.cmi.2015.03.011) (Sections 
1 and 6.1). 
Updated the timing of allogeneic cell transplantation in Inclusion Criterion #2 from ≥21 
days prior to randomization to ≥21 days prior to dosing (Sections 1 and 6.1).  
Updated the exclusion on prior therapy with anti-thymocyte globulin, alemtuzumab 
(Campath®), or other immunosuppressive T cell monoclonal antibodies (Exclusion 
Criterion 8) to within 28 days prior to dosing (Sections 1 and 6.2). 
Updated the exclusion on prior donor lymphocyte infusion or CD34+ stem cell infusion 
(Exclusion Criterion 9) to within 21 days prior to dosing (Sections 1 and 6.2). 
Rationale: Dosing is a more appropriate milestone for inclusion/exclusion for the above 
criteria  
Updated Exclusion Criterion 11 and related text to allow the use of maribavir for CMV 
(Sections 1, 6.2, and 7.7.1).  
Rationale: Maribavir has recently been approved in some, but not all regulatory 
jurisdictions for the treatment of CMV infections and is therefore no longer considered to 
be an investigational antiviral agent. It is not considered to have anti-AdV activity.  
Updated Exclusion Criterion 12 to exclude pregnant females (Sections 1 and 6.2). 


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Updated Exclusion Criterion 14 and related text to provide more clarification on allergies 
to posoleucel or blood transfusion products that would preclude study participation 
(Sections 1, 5.1, and 6.2). 
Updated Exclusion Criterion 15 to provide an exception for patients with no clinical or 
radiological manifestations of COVID-19 if the Investigator and Sponsor Medical 
Monitor concur on their enrollment (Sections 1 and 6.2).  
Rationale: As the COVID-19 pandemic has evolved, investigators at clinical sites are 
reporting that they are treating HCT recipients who have persistently positive SARS-
CoV-2 laboratory tests, but who do not appear to have clinically-significant disease 
attributable to SARS-CoV-2. In select cases, these patients may be eligible to participate 
in this study, and the exclusion criterion has been updated to reflect this. 
• Added flexibility in blood specimen testing to allow blood specimen results from 
local laboratory results to be used for confirmation of eligibility and dosing if AdV 
viral load results from the central laboratory are not available (Sections 1, 2, and 
9.1.1). 
Simplified blood specimen collection and testing by allowing sites to initiate screening 
activities based off specimens collected locally within 3 days of screening  
Added language to allow participants to be randomized and dosed (with Sponsor Medical 
Monitor approval) based on local laboratory AdV viremia results if the central laboratory 
screening viremia result is not yet available at the time of intended dosing 
Rationale: AdV infections in HCT recipients may progress rapidly. In order to prevent 
delays in randomization or dosing of otherwise eligible patients that may be caused solely 
by delays in obtaining AdV viral load results from the central laboratory, patients may 
enter the study based on local laboratory viral load data. In all cases, as before, all 
assessments of efficacy relating to AdV viral load values will use values from the central 
laboratory.   
• Expanded the screening window 
Screening window expanded from 10 days to 21 days (Day -21 to Day -1) (Section 2).  
Rationale: This change was made based on feedback from clinical sites that indicated 
operational challenges in completing all screening procedures within the narrow 10 day 
window. 
• Added clarifying information regarding premature Crossover  
Added text to clarify that participants with premature cross-over (ie, prior to Day 29) will 
be expected to have received both infusions of study treatment before evaluation by the 
Adjudication Committee (Section 5.1).  
Rationale: Added at the request of the Adjudication Committee who will be adjudicating 
the eligibility of these participants for crossover. 
• Added DSMB review and recommendation of preliminary safety data from 5 
participants ≥1 and ≤6 years of age prior to enrolling participants under age 1 


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Rationale: Removed the requirement for a protocol amendment prior to enrolling pts <1yr 
to reduce the operational burden for the sites. In place of a protocol amendment to 
support this change, the safety data from patients in the 1 – 6 year old age range will be 
reviewed by the DSMB before opening the study to participants <1 year of age. Once this 
decision to proceed has been made by the DSMB, it will be communicated to clinical 
sites, IRBs/ERCs, and regulatory agencies as appropriate. 
• Statistical Updates 
Updated text to indicate that there will not be a separate SAP for the interim analysis, and 
that the study SAP will be finalized prior to the interim analysis (Sections 10.1 and 10.3).  
Rationale: Separate documents for these analyses are no longer considered to be 
necessary, and all the information will be consolidated into a single SAP document that 
will be finalized prior to any interim analysis. 
Added a sentence to indicate that the primary and key secondary efficacy endpoints will 
be analyzed under the estimand framework (Section 10.3.1). 
Removed details on missing data imputation and, instead, referred to the SAP for this 
information (Section 10.3.1.1). 
Added language to clarify that the key secondary efficacy endpoint will be tested 
sequentially after the primary endpoint reaches statistical significance (Sections 1 and 
10.3.1.2). 
Deleted the Other Analyses section (formerly Section 10.3.3), as these will be detailed in 
the SAP. 
Updated language regarding the interim analysis to indicate that there will not be a 
separate SAP for the interim analysis and clarified language regarding the roles of the 
independent statistician and the DSMB and on maintaining the blind (Section 10.3.3). 
• Added language regarding premedication with an antihistamine 
Text was added to allow premedication with an antihistamine similar to diphenhydramine 
that is preferred by the study site, and to allow diphenhydramine/acetaminophen doses 
that are routinely used at these sites to be used for participants with a prior history of 
reaction to blood products (Sections 7.1 and 7.1.1).  
Rationale: Some clinical sites routinely use antihistamines other than diphenhydramine 
for this purpose. In some cases, clinical sites routinely use standard doses for these pre-
medications that are slightly different than the doses indicated in the protocol. 
• Streamlined study drug administration and dosing instructions  
IP preparation and infusion procedure description has been removed from the protocol, 
and referral to the Cell Therapy Manual has been added. (Section 7.1) 
Rationale: Investigational product management is more extensively described in the Cell 
Therapy Manual. 
• Updated text to clarify that no subsequent infusion of blinded study treatment 
should occur in participants who develop new onset GVHD (Grade >2) or 
worsening of GVHD (Section 7.2). 


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• Added Clarifying information regarding Target Disease Endpoint Definitions  
Added AdV carditis as a manifestation that will be adjudicated by the Adjudication 
Committee for target organ disease (Section 9.1.2 and Appendix 8). 
Updated the target disease endpoint definitions and added text to indicate that the 
definitions may be modified by the Adjudication Committee and updated version will be 
recorded in the Adjudication Committee charter (Appendix 8). 
Rationale: Carditis was added as a manifestation after an initial meeting with the 
Adjudication Committee. The added text relating to clinically significant viremia is 
intended to provide clarification that the definition is intended to apply to those 
participants whose clinically-significant viremia at study entry resolves, but who 
subsequently develop a recurrence of AdV infection, which will need to be adjudicated 
using the criteria in Appendix 8 
Miscellaneous revisions to reflect administrative changes, correct typographical errors, 
correct inconsistencies within other study documents and addition of clarifying 
information 
• Updated the sponsor’s address and contact information (Title Page, Section 1). 
• Added clarifying information regarding “recurrence dose” timing and assessments  
• Added United States Adopted Name and International Nonproprietary Name, posoleucel, 
in lieu of ALVR105 
• Added clarification that AEs to be captured for the primary safety endpoint are those that 
are treatment-emergent (Sections 1, 4, and 10.3.2). 
• Minor changes involving grammar, wordsmithing, inconsistencies, and punctuation, as 
well as other minor editorial changes to improve clarity were made throughout the 
document 
Amendment 1 Rationale 
This amendment was made in response to regulatory agency feedback. Additional changes were 
made to correct errors and to provide additional clarity. 
Major revisions include: 
• Labeled safety objectives and endpoints as primary (Sections 1 and 4). 
• Added a requirement for participants who receive a third dose for recurrence to undergo 
safety follow-up for 20 weeks after the third dose of study treatment (Sections 1 and 5.1). 
• Added a statement that participating sites will adhere to the relevant safety standards of 
FACT and JACIE (Section 5.1). 
• Added a statement that participants will be approached for enrollment in a long-term 
registry study (Section 5.3). 
• Provided additional guidance on permitted and prohibited medications and the recording 
of concomitant medications (Section 7.7). 


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• Updated text such that any participant who develops irreversible, life-threatening, Grade 
3 to 4 acute GVHD or a Grade 3 to 4 non-hematologic adverse event between the first 
and any subsequent dose of posoleucel or placebo that is considered related to study 
treatment administration should discontinue study treatment (Section 8.1). 
• Added the Intent-to-Treat Population; all efficacy endpoints will be analyzed based on 
the Intent-to-Treat Population, and these analyses will be considered the primary analyses 
of efficacy (Sections 1, 10.2, and 10.3.1). 
• Deleted the Modified Intent-to-Treat Population (Sections 1, 10.2, and 10.3.1). 
• Updated the planned analysis of the primary efficacy endpoint to be analyzed based on 
logistic regression instead of Fisher’s exact test. The model will include a term for 
treatment and, in order to take the randomization stratification variables into account, the 
following covariates: level of viremia (≥10,000 copies/mL or <10,000 copies/mL AdV 
DNA) and age (≥12 years or <12 years) (Sections 1 and 10.3.1.1). 
• Provided justification for analysis of the primary efficacy endpoint at Day 29 and for 
durability of response assessments (Section 5.4). 
• Added weekly AdV viral load detection in urine for patients with clinical signs and/or 
symptoms of AdV hemorrhagic cystitis until resolution of hemorrhagic cystitis 
(Sections 2 and 9.1.1, and Appendix 3). 
• Added assessment of coagulation parameters (PT, INR, and PTT) at Days 1 and 29 of the 
Primary Study Period and Days 1’ and 29’ of the Cross-Over Period (Section 2 and 
Appendix 3). 
• Provided additional clarification on timing of pregnancy testing relative to study 
treatment administration on Day 15 and added pregnancy testing to the Week 10 (Week 
10’), Week 16 (Week 16’), Week 24 (Week 24’), and ET visits (Sections 2 and 9.3.1; 
Appendix 3). 
• Updated the timing of the first visit of the Cross-Over Period from Week -6’ to -1’ 
(Day -42’ to -1’) to Week -2’ to -1’ (Day -10’ to -1’) (Section 2). 
• Provided clarification that any evaluations required at the Day -10’ to -1’ visit of the 
Cross-Over Period do not have to be repeated if completed within 10 days as part of the 
Primary Study Period (Section 2). 
• Removed the assessment of adenovirus viral load in nasopharyngeal swab from the 
Day -10’ to -1’ visit of the Cross-Over Period (Section 2). 
• Added an assessment of aGVHD at Day 1 (Day 1’) (Section 2). 
• Updated language for stool collection to clarify that Screening, Day 1 (Day 1’) and 
Day 29 (Day 29’) collection is required for all patients, but collection at other timepoints 
is required only if the participant has symptoms; however, collection at these other 
timepoints should be collected in all participants if feasible (Section 2). 
• Provided clarity on timing of radiological imaging during the Cross-Over Period 
(Sections 1, 2, and 9.1.3). 


AlloVir 
Clinical Study Protocol P-105-303 
Confidential & Proprietary 
 
Version 5.0, 30 November 2023 
105 
• Provided details on interim analyses and timing of finalizing both the interim analysis 
SAP and the main SAP relative to conducting interim analyses (Sections 1, 10.3, 10.3.3, 
and 10.3.4). 
• Added additional guidance on post-infusion monitoring (Section 9.3.7). 
• Added a statement that all protocol amendments will be submitted to regulatory 
authorities and ethics committees/IRBs as appropriate (Appendix 2). 
• Added a statement that in some jurisdictions, legally effective informed consent must be 
obtained from all legal guardians for minor patients (Appendix 2). 
• Provided guidance on estimating fraction of inspired oxygen (Sections 1 and 6.2; 
Appendix 9). 



SAP_001.pdf: 
Protocol Number: P-105-303 
 
Official Title:  
Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, with Cross-Over, of Posoleucel 
(ALVR105) for the Treatment of Adenovirus Infection in Pediatric and Adult Participants Receiving 
Standard of Care Following Allogeneic Hematopoietic Cell Transplantation 
 
NCT Number: NCT05179057 
 
Document Date: 12 January 2024 


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        Version 1.0, 12 January 2024 
 
STATISTICAL ANALYSIS PLAN  
Protocol Title: 
Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, 
with Cross-Over, of Posoleucel (ALVR105) for the Treatment of 
Adenovirus Infection in Pediatric and Adult Participants 
Receiving Standard of Care Following Allogeneic 
Hematopoietic Cell Transplantation 
 
Protocol Number: 
P-105-303 
Protocol Version/Date: 
Amendment 4, 30 November 2023 
Investigational Product: 
Posoleucel (ALVR105) 
 
 
Sponsor: 
AlloVir 
1100 Winter Street 
Waltham, MA  02451 
United States 
 
 
SAP Version/Date: 
V1.0/12 January 2024 
 
CONFIDENTIAL 
The information in this document is confidential and is not to be disclosed without the written 
consent of 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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Statistical Analysis Plan 
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        Version 1.0, 12 January 2024 
 
SIGNATURE PAGE  
Protocol Title: 
Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial, 
with Cross-Over, of Posoleucel (ALVR105) for the Treatment of 
Adenovirus Infection in Pediatric and Adult Participants 
Receiving Standard of Care Following Allogeneic Hematopoietic 
Cell Transplantation 
Protocol Number: 
P-105-303 
SAP Version/Date: 
V1.0/12 January 2024 
We, the undersigned, have reviewed and approved this Statistical Analysis Plan: 
 
 
Signature 
 
 
 
 
 
 
 
 
 
AlloVir, LLC 
 
 
 
 
 
 
 
 
 
 
AlloVir, LLC  
 
 
 
 
 


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Statistical Analysis Plan 
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        Version 1.0, 12 January 2024 
 
TABLE OF CONTENTS 
1 
INTRODUCTION ...................................................................................................5 
2 
STUDY OVERVIEW .............................................................................................5 
2.1 
Study Objectives ......................................................................................................5 
2.1.1 
Primary Objective ...................................................................................................5 
2.2 
Study Design ............................................................................................................5 
2.2.1 
Overview ..................................................................................................................5 
2.2.2 
Method of Treatment Assignment .........................................................................7 
2.2.3 
Blinding ....................................................................................................................7 
2.2.4 
Sample Size Determination ....................................................................................7 
2.3 
Study Endpoints ......................................................................................................8 
2.3.1 
Primary Efficacy Endpoint ....................................................................................8 
2.3.2 
Safety Endpoints .....................................................................................................8 
3 
STATISTICAL METHODOLOGY ......................................................................8 
3.1 
General Considerations ..........................................................................................8 
3.1.1 
Study Day .................................................................................................................8 
3.1.2 
Analysis Visits ..........................................................................................................9 
3.1.3 
Definition of Baseline ..............................................................................................9 
3.1.4 
Handling of Dropouts and Missing Data ..............................................................9 
3.2 
Analysis Populations ...............................................................................................9 
3.2.1 
Intent-to-Treat (ITT) Population ..........................................................................9 
3.2.2 
Modified Intent-to-Treat (mITT) Population .......................................................9 
3.2.3 
Safety Population ....................................................................................................9 
3.3 
Participant Data and Study Conduct ..................................................................10 
3.3.1 
Participant Disposition .........................................................................................10 
3.3.2 
Demographic and Baseline Characteristics ........................................................10 
3.3.3 
Prior and Concomitant Medications/Procedures ...............................................10 
3.4 
Efficacy Analyses ...................................................................................................11 
3.4.1 
Primary Efficacy Endpoint Analysis ...................................................................11 
3.4.2 
Primary Analysis of Primary Efficacy Endpoint ...............................................11 
3.5 
Safety Analyses ......................................................................................................11 
3.5.1 
Adverse Events (AEs) ...........................................................................................12 
3.5.2 
AEs of Special Interest ..........................................................................................12 
3.5.3 
Clinical Laboratory Tests .....................................................................................13 
3.6 
Data Safety Monitoring Board .............................................................................13 
3.7 
Interim Analysis ....................................................................................................13 
 
 
 


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LIST OF ABBREVIATIONS  
Abbreviation 
Definition 
AdV 
Adenovirus 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
CRF 
Case Report Form 
CRS 
Cytokine Release Syndrome 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events  
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
GVHD 
Graft Versus Host Disease 
HCT 
Hematopoietic Cell Transplant 
HHV-6 
Human Herpesvirus 6 
HLA 
Human Leukocyte Antigen 
JCV 
JC Virus 
LFT 
Liver Function Test 
LLOQ 
Lower Limit of Quantitation 
MedDRA 
Medical Dictionary for Regulatory Activities 
OL 
Open Label 
PBMC 
Peripheral Blood Mononuclear Cell 
PT 
Preferred Term 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
WHO 
World Health Organization 
 
 


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1 
INTRODUCTION  
This document details the analysis plan for the study entitled “Phase 3, Randomized, Double-
Blind, Placebo-Controlled Trial, with Cross-Over, of Posoleucel (ALVR105) for the Treatment of 
Adenovirus Infection in Pediatric and Adult Participants Receiving Standard of Care Following 
Allogeneic Hematopoietic Cell Transplantation”. It is based on Protocol P-105-303 Amendment 
4 dated 30 November 2023 and describes the proposed efficacy and safety analyses. Since the 
study is terminated due to futility, only the primary efficacy endpoint and selected safety endpoints 
will be analyzed.  
The Statistical Analysis Plan (SAP) will be finalized prior to interim database lock. After the 
database lock, any deviation from the SAP will be documented in the final Clinical Study Report 
(CSR).  
2 
STUDY OVERVIEW  
2.1 
Study Objectives  
2.1.1 
Primary Objective  
The primary efficacy objective of this trial is to compare the percentage of participants who have 
clearance of Adenovirus (AdV) viremia at Day 29 in participants receiving posoleucel and 
standard of care (SoC) to that in participants receiving placebo and SoC. 
The primary safety objective is to determine the safety and tolerability of posoleucel cells by 
analyzing the incidence and severity of treatment-emergent adverse events (TEAEs), including 
individual AEs of special interest (AESIs). 
2.2 
Study Design  
2.2.1 
Overview  
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to assess the 
safety and efficacy of posoleucel as compared to placebo for the treatment of AdV infection in 
pediatric and adult recipients of HCT with AdV infections receiving SoC.  
Approximately 80 participants may be randomized 
 to receive 
 infusions of 
posoleucel or placebo 
). Randomization will be stratified 
 
 
It is expected that no more than 30% of participants, but at least 10% of participants, will be 
 
 Enrollment of participants <1 year of age will occur once preliminary safety data are 
available from 5 participants ≥1 and ≤6 years of age. The Data Safety Monitoring Board (DSMB) 
will review data through Day 29 from these 5 participants once available and make a 
recommendation. A formal memo will be provided to ethics committees and sites once the DSMB 
approves enrollment of participants <1 year of age. 
The Primary Study Period is 4 weeks (28 days) for evaluation of efficacy, including the primary 
endpoint, plus 20 weeks for safety follow-up, for a total study duration of 24 weeks. For 
participants who cross over, the Cross-Over Period is 4 weeks (28 days), plus 20 weeks for safety 


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follow-up. Participants who experience recurrence and receive an additional dose will have safety 
follow-up for 20 weeks after the final dose.  
Participants who progress to active target organ disease or whose existing target organ disease 
progresses (as assessed by the Investigator and Sponsor Medical Monitor and based on the criteria 
in Appendix 8 of the protocol) between Day 29 and Week 10 will be considered to have 
experienced progression and will have the option to be crossed over to the alternate treatment arm. 
Participants can cross over before Day 29 only if they progress with target organ disease as 
adjudicated by the Adjudication Committee. Cross-over participants will receive the alternate 
treatment to which they were originally randomized, posoleucel or placebo 
 sequential infusions 
separated by 
 ± 3 days), but study treatment will remain blinded.  
Participants who demonstrate viral clearance by Day 29 of the Primary Study Period but later 
exhibit a clinically significant recurrence of AdV viremia (i.e., ≥10,000 copies/mL AdV DNA at 
the central laboratory) and/or progression of or to active organ disease, will be eligible for an 
additional dose of the last received therapy (posoleucel or placebo) for recurrence prior to 20 
weeks. These participants will continue to have safety follow-up for an additional 20 weeks after 
administration of the additional dose.  
A summary of the study design is shown in Figure 1.  
 
Figure 1. Summary of Study Design 
 


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2.2.2 
Method of Treatment Assignment  
Participants who meet all the inclusion criteria and none of the exclusion criteria will be 
randomized to the study prior to Day 1 of the Primary Study Period. Participants will be 
randomized 
 to receive 
 infusions of posoleucel or placebo. 
Randomization will be stratified 
 
 
2.2.3 
Blinding  
The Sponsor designee (e.g., interactive response technology [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 (e.g., staff involved in suspected unexpected serious adverse reaction (SUSAR) 
reporting). 
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 (AE) 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. 
2.2.4 
Sample Size Determination  
The required sample size is 82 participants based on the below specifications that have received at 
least 1 dose of posoleucel or PBO.  
The sample size was determined based on the following specifications: 
1. Superiority study comparing posoleucel plus SoC to placebo plus SoC 
2. Primary endpoint is success or failure based on clearance of AdV viremia at Day 29 visit 
of the Primary Study Period 
3. Allocation (posoleucel:placebo) is
 
4. Chi-square test  
5. Two-sided alpha = 0.05 
6. True success rate (defined as clearance of virus) for posoleucel = 0.50 
7. True success rate (defined as clearance of virus) for placebo = 0.25 
8. Power = 80% 


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A SSRE and futility analysis will be performed after approximately 40 participants have completed 
Day 29 of the Primary Study Period. Details of the SSRE and futility analysis will be provided in 
the SSRE Plan prior to conducting the interim analyses. 
2.3 
Study Endpoints  
2.3.1 
Primary Efficacy Endpoint  
The primary efficacy endpoint is the proportion of participants with undetectable viremia (less 
than lower limit of quantitation [LLOQ]) at Day 29.  
2.3.2 
Safety Endpoints  
The safety endpoint is the incidence and severity of TEAEs, including adverse events of special 
interest (AESIs), during the study. 
The clinical laboratory evaluations (hematology, chemistry, and urinalysis) will also be 
summarized. 
3 
STATISTICAL METHODOLOGY  
3.1 
General Considerations  
The statistical analysis of the data obtained from this study will be performed using SAS® version 
9.4 or higher.   
Data collected in this study will be documented using summary tables and subject data listings. 
Continuous variables will be summarized using descriptive statistics, specifically the number of 
non-missing observations, mean, standard deviation, median, minimum, and maximum. 
Categorical variables will be summarized using the frequency count and the percentage of 
participants in each category. For continuous data, the minimum and the maximum will use the 
same decimal place accuracy as the raw data.  The mean, median, and standard deviation will use 
one more decimal place than the raw data.  For categorical data, percentages will be reported to 
one decimal place.   
Summary statistics will be presented by randomized or actual treatment group for the Primary 
Study Period. The key efficacy and selected safety endpoints will be summarized for the Primary 
Study Period.  
No hypothesis tests will be performed.   
3.1.1 
Study Day  
Study day will be calculated from the date of first dose of study drug, as actual visit date – first 
dose date for dates before the first dose date and +1 for dates on or after the first dose date. The 
day of the first dose of study drug will be Day 1, and the day immediately before and after Day 1 
will be Day -1 and Day 2.  
For participants who crossed over, the first dosing date of the Cross-Over Period will be Day 1’ 
for that period. Study day of the Cross-Over Period will be calculated as actual visit date in the 
Cross-Over Period – Cross-Over Period Day 1’ + 1.  


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3.1.2 
Analysis Visits  
Subject visits might not occur on protocol-specified days. Therefore, for the purpose of analysis, 
all scheduled, unscheduled, and early termination visits will be assigned to analysis visits 
according to the analysis windows (Appendix 1) based on study days. If there is more than 1 
assessment in an analysis window, the assessment closest to the target day will be used in the 
analysis. If there are 2 assessments in a window equidistant from the target day, the later 
assessment will be used in the analysis.  
3.1.3 
Definition of Baseline  
Baseline is defined as the last non-missing measurement prior to the first dose of study treatment. 
This can be on Day 1 as long as the measurement is taken prior to the first dose. 
3.1.4 
Handling of Dropouts and Missing Data  
In general, data will be analyzed and presented as observed and will not be imputed for the analysis 
of efficacy and safety, unless otherwise specified. The missing data handling for the primary 
efficacy endpoints is discussed in Section 3.4. 
In case the start and end dates for adverse events and concomitant medications/procedures are 
missing or incomplete, the missing component(s) will be assumed as the most conservative value 
possible. For example, AEs with missing start dates, but with stop dates either overlapping into 
the treatment period or missing, will be counted as treatment-emergent, taking the worst-case 
approach. When partial dates are present in the data, both a partial start date and/or a partial stop 
date will be evaluated to determine whether it can be conclusively established that the AE started 
prior to the start of study treatment or ended prior to the start of study treatment. If the above 
cannot be conclusively established based on the partial and/or present dates, then the AE will be 
considered as treatment-emergent. Actual data values as they appear in the original case report 
forms (CRFs) will be presented in the data listings. 
3.2 
Analysis Populations  
3.2.1 
Intent-to-Treat (ITT) Population  
The ITT Population will include all randomized participants and will be used for listings.  
3.2.2 
Modified Intent-to-Treat (mITT) Population  
The mITT Population will include all randomized participants who receive at least one dose of 
posoleucel or placebo. All efficacy endpoints will be analyzed based on the mITT Population. 
Participants will be analyzed according to the randomized study treatment.  The efficacy analysis 
will be based on the mITT population.  
3.2.3 
Safety Population  
The Safety Population will include all participants who receive any amount of posoleucel or 
placebo. All safety analyses will be based on the Safety Population. Participants will be analyzed 
according to the actual study treatment received. All safety analyses will be based on the Safety 
Population.  


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3.3 
Participant Data and Study Conduct  
3.3.1 
Participant Disposition  
Participant disposition information will be summarized using the Enrolled Population (all 
participants who sign the informed consent form). The numbers and percentages of participants 
who were screened, screen failure along with the reasons of screen failure, randomized, 
randomized and not dosed, dosed, completed study drug, discontinued study drug early along with 
the reasons for early discontinuation of study drug, entered Cross-Over, completed the study, and 
discontinued the study early along with the reasons for early discontinuation of study. The study 
and study drug disposition will be summarized for the Primary Study Period and the Cross-Over 
Period. The numbers and percentages of recurrence participants will be summarized. The number 
of participants who received any study treatment will be summarized by the number of infusions. 
By-participant listings will also be provided for participant disposition. 
3.3.2 
Demographic and Baseline Characteristics  
Demographic (age and age subgroups [e.g. 0 to <2y; 2-<6y; 6 to <12y; 12 to <18; <65, >=65, sex, 
race, and ethnicity), baseline characteristics (height, weight, BMI), and randomization 
stratification factors will be summarized with descriptive statistics or counts and percentages of 
participants as appropriate for mITT Population.  
The following disease characteristics will also be summarized using frequencies and percentages 
or descriptive statistics:  
• Baseline Weight (kg) (overall, Age >/≤ 18 years) 
• Baseline Height (cm) (overall, Age >/≤ 18 years) 
• Baseline BMI (kg/m²) (overall, Age >/≤ 18 years) 
• Baseline Target Organ Disease Diagnosis, n (%) 
• Screening AdV Viremia, n (%) 
• Baseline AdV Viremia, n (%) 
• Baseline Viremia, n (%) 
• Use of Cidofovir at Baseline, n (%) 
• Hematopoietic Cell Transplantation Donor Type, n (%) 
• Time (Days) from Hematopoietic Cell Transplantation at Screening 
• Type of Conditioning Regimen, n (%) 
• Reduced intensity conditioning regimen  
• Any aGVHD at Screening, n (%) 
• Any cGVHD at Screening, n (%) 
• Donor Recipient HLA Match, n (%) 
3.3.3 
Prior and Concomitant Medications/Procedures  
Concomitant medications will be coded to anatomical therapeutic chemical (ATC) class and 
preferred term using the WHODrug Dictionary. All medications taken prior to the first dose of 
study treatment will be considered as prior medications. The medications taken prior to the first 
dose of study treatment and were ongoing or started on or after the first dose of study treatment 
will be considered as concomitant medications. 


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The numbers and percentages of participants taking prior and concomitant medications by ATC 
class and preferred term will be summarized based on the Safety Population. 
3.4 
Efficacy Analyses  
Only the primary efficacy endpoint will be summarized for the primary treatment period based on 
the mITT Population.  
For AdV viral endpoints at Day 29 or Week 4 visit, a +14-day window will be applied to the Day 
29 visit. The last observed plasma AdV DNA result through Day 29 + 14 days (up to 43 days 
post first infusion) will be used for the analysis for all the participants including those who 
crossover from PSL to placebo. For participants who crossover from placebo to PSL, the pre-
dose cross-over Day 1 viral load may be used. Participants who cross over on or before Day 29 
will be treated as failure. 
3.4.1 
Primary Efficacy Endpoint Analysis  
3.4.2 
Primary Analysis of Primary Efficacy Endpoint  
The primary efficacy endpoint, undetectable viremia (less than LLOQ) at Day 29 of the Primary 
Study Period, will be summarized by treatment group using the count and percentage, together 
with an exact (Clopper-Pearson) 95% confidence interval for the true percentage. The difference 
in percentages between the two treatments (posoleucel – placebo), together with a 95% exact 
confidence interval for the true difference, will be presented.  
This endpoint will be analyzed using logistic regression. The model will include a term for 
treatment and the following covariates: level of viremia at Baseline (≥10,000 copies/mL or 
<10,000 copies/mL AdV DNA), age (≥12 years or <12 years) and absolute lymphocyte count at 
Baseline. For participants who discontinued treatment but remain on the study, data collected after 
treatment discontinuation will be included in the analysis.  If a participant doesn’t have plasma 
AdV DNA result in the Day 29 through Day 43 window but has undetectable viremia before Day 
29 and after Day 43, it will be imputed as success for the primary endpoint. The deaths related to 
adenovirus infection on or before Day 29 will be imputed as failure.   
Subgroup analyses of the primary endpoint will be performed for both of the randomization 
stratification variables: (1) level of viremia: ≥10,000 copies/mL and <10,000 copies/mL AdV 
DNA and (2) age: ≥12 years or <12 years. 
3.5 
Safety Analyses  
Safety will be analyzed and compared between treatments received based on data from the Primary 
Study Period. No formal comparisons will be made between these groups. 
All safety analyses will be based on the Safety Population. 
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 of non-missing observations, arithmetic mean, standard deviation, median, minimum, and 
maximum). 


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3.5.1 
Adverse Events (AEs)  
All AEs will be coded to system organ class and preferred term using MedDRA. A treatment-
emergent adverse event (TEAE) is defined as an adverse event with a start date and time on or 
after the administration of investigational product or placebo or that worsened in severity after 
administration of investigational product or placebo through the end of the study.  
An overall summary of AEs will be provided with the number and percentage of participants who 
experienced at least one (1) AE or TEAE in the following categories: 
• 
Any TEAEs 
• 
Any TEAEs by severity 
• 
Any treatment-related TEAEs 
• 
Any treatment-related TEAEs by severity  
• 
Any treatment-emergent AESI (TEAESIs) 
• 
Any treatment-emergent serious AEs (TESAEs) 
• 
Any treatment-related TESAEs 
• 
Any TEAEs leading to discontinuation of study treatment 
• 
Any TEAEs leading to discontinuation of study, and 
• 
Any AEs leading to death 
The numbers and percentages of participants will also be presented by system organ class (SOC) 
and preferred term (PT) for each of the TEAE categories in the summary. Participants with 
multiple AEs will be counted only once per SOC and PT. 
Listings will be presented specifically for any AEs, SAEs, AESIs, and AEs leading to 
discontinuation of study treatment and study. 
3.5.2 
AEs of Special Interest  
The AESIs will be reviewed by the DSMB as per the DSMB Charter. Criteria for acute and chronic 
GVHD and CRS can be found in Protocol Appendix 6 and 7, respectively.  
The number and percentage of participants who had the treatment-emergent AESIs will be 
summarized by treatment group for the Primary Study Period and by cross-over treatment group 
for the Cross-Over Period: 
• 
Severity and incidence of acute GVHD 
• 
Severity and incidence of chronic GVHD 
• 
Severity and incidence of CRS (ASTCT Score) 
• 
Severity and incidence of infusion-related AEs 
• 
Severity and incidence of graft failure and rejection 


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3.5.3 
Clinical Laboratory Tests  
Clinical laboratory data (hematology, clinical chemistry, and routine urinalysis) from the Primary 
Study Period will be summarized by laboratory test, visit, and treatment group using descriptive 
statistics. The changes from baseline to each post-baseline visit will also be summarized.    
Listings will be presented for selected laboratory data and the test values outside the normal range 
will be flagged.  
3.6 
Data Safety Monitoring Board  
An independent Data and Safety Monitoring Board (DSMB) will be convened for this study to 
routinely monitor participant safety. The DSMB will receive summary reports of all unexpected 
SAEs at least monthly. A DSMB charter, detailing all aspects of the DSMB’s composition, scope 
of review, and procedures will be provided separately. 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. 
3.7 
Interim Analysis  
A Sample Size Re-Estimation (SSRE) and futility analysis will be performed after approximately 
40 participants have completed Day 29 of the Primary Study Period. Details of the SSRE and 
futility analysis will be provided in the SSRE Plan prior to conducting the interim analyses. 


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Appendix 1 
Analysis Visit Windows  
Table 1 
Analysis Visit Windows for Adenovirus Viral Load Data 
Nominal Visit 
Nominal Study Day 
Visit Window Study Day 
Lower Limit 
Upper Limit 
Day 1/Baseline 
1 
 
≤1 
Week 1 
8 
2 
11 
Week 2 
15 
12 
18 
Week 3 
22 
19 
25 
Week 4 
29 
26 
32 
Week 5 
36 
33 
39 
Week 6 
43 
40 
57 
Week 10 
71 
58 
92 
Week 16 
113 
93 
141 
Week 24 
169 
>141 
 
Table 2. 
Analysis Visit Windows for Other Viral Load and Clinical Lab 
Nominal Visit 
Nominal Study Day 
Visit Window Study Day 
Lower Limit 
Upper Limit 
Day 1/Baseline 
1 
 
≤1 
Week 1 
8 
2 
11 
Week 2 
15 
12 
22 
Week 4 
29 
23 
36 
Week 6 
43 
37 
57 
Week 10 
71 
58 
92 
Week 16 
113 
93 
141 
Week 24 
169 
>141 
 
 


Signature Page for P-105 303 Final SAP v1.0 for abbreviate CSR
VV-CLIN-000364 v1.0
Signature Page for P-105 303 Final SAP v1.0 for abbreviate CSR
VV-CLIN-000364 v1.0
Approval Task
ics
12-Jan-2024 19:11:42 GMT+0000
Approval Task
12-Jan-2024 21:26:04 GMT+0000