Phase 1/2, Double-Blind, Placebo-Controlled, Dose Escalation and Expansion Study of ALVR106 in Addition to Standard of Care for the Treatment of High-Risk Patients With Respiratory Viral Infections After Hematopoietic Cell and Solid Organ Transplant
Phase: PHASE1
Conditions: Respiratory Tract Viral Infections, Human Metapneumovirus (hMPV) Infection, Parainfluenza (PIV) Infection, Respiratory Syncytial Viral (RSV) Infection, Influenza Infection
Sponsor: AlloVir

Protocol Number: P-106-001 
 
Official Title:  
 Phase 1/2, Double-Blind, Placebo-Controlled, Dose Escalation and Expansion Study of ALVR106 in 
Addition to Standard of Care for the Treatment of High-Risk Patients with Respiratory Viral 
Infections After Hematopoietic Cell or Solid Organ Transplant 
 
NCT Number: NCT04933968 
 
Document Date: 19 May 2022 

 
 
 
 
 
 
 
 
 
 
CLINICAL STUDY PROTOCOL 
 
Phase 1/2, Double-Blind, Placebo-Controlled, Dose Escalation and 
Expansion Study of ALVR106 in Addition to Standard of Care for 
the Treatment of High-Risk Patients with Respiratory Viral 
Infections After Hematopoietic Cell or Solid Organ Transplant 
Investigational Product: ALVR106 
Protocol Number: P-106-001 
 
 
 
Sponsor: 
AlloVir 
Kirby Grove 
2925 Richmond Avenue, Suite 1200 
Houston, TX 77098 
United States 
Telephone: 936-662-3626 
Fax: 979-289-7437 
 
 
Version Number: 5.0 
Date:  19 May 2022 
 
 
 
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 and study personnel 
directly involved with conducting this protocol. Persons to whom the information is disclosed 
must be informed that the information is confidential and proprietary to AlloVir and that it may 
not be further disclosed to third parties. 
 

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

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SYNOPSIS 
TITLE:  Phase 1/2, Double-Blind, Placebo-Controlled, Dose Escalation and Expansion Study of 
ALVR106 in Addition to Standard of Care for the Treatment of High-Risk Patients with 
Respiratory Viral Infections After Hematopoietic Cell or Solid Organ Transplant 
PROTOCOL NUMBER:  P-106-001 
IND NUMBER:  19723 
INVESTIGATIONAL PRODUCT:  ALVR106 
PHASE:  1/2 
OBJECTIVES: 
Part A (Dose Escalation) 
The primary objective of Part A is to determine the safety and tolerability of ascending doses of 
ALVR106 when administered to high-risk adult patients with upper respiratory tract infections 
(URTIs) caused by respiratory syncytial virus (RSV), influenza virus (IFV), human 
metapneumovirus (hMPV), and/or parainfluenza virus (PIV) following HCT or SOT. 
The secondary objectives of Part A are the following: 
• To identify the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) 
of ALVR106 in patients with URTIs 
• To characterize the individual patient antiviral response as measured by change in viral load 
from nasal swab specimens from baseline through Day 28 following the patient’s first 
ALVR106 infusion  
Part B (Recommended Phase 2 Dose Cohort Expansion) 
The primary objective of Part B is to determine the antiviral activity of the RP2D of ALVR106, 
as compared to placebo, when administered to high-risk adult patients with URTIs caused by RSV, 
IFV, hMPV, and/or PIV following HCT or SOT. 
The secondary objectives of Part B are the following: 
• To determine the safety and tolerability of the RP2D of ALVR106 when administered to 
high-risk adult patients with URTIs caused by RSV, IFV, hMPV, and/or PIV following HCT 
or SOT 
• To characterize the individual patient antiviral response as measured by the percent reduction 
in viral load from nasal swab specimens and a reduction in clinical signs and symptoms from 
baseline through Day 28, Day 60, Day 90, and Month 6 following the patient’s first ALVR106 
infusion  
Reference Protocol Section 2 for additional study objectives. 

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POPULATION: 
Key Inclusion Criteria 
• Aged 17 to 75 years at screening. 
• Undergone hematopoietic cell transplantation (HCT) ≥21 days or solid organ transplantation 
(SOT) ≥28 days prior to study treatment administration  
• Detection of at least 1 target virus of interest (ie, RSV, IFV, hMPV, and/or PIV) in the 
respiratory tract  
• Diagnosis of respiratory tract infection, defined by new onset of symptoms 
Key Exclusion Criteria 
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose 
>0.5 mg/kg/day) within 7 days prior to screening  
• Prior therapy with abatacept or belatacept, within 3 months of screening; or antithymocyte 
globulin (ATG), alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted 
monoclonal antibodies within 28 days of study treatment administration  
• Infection with coronavirus disease 2019 (COVID-19) within 28 days prior to study treatment 
administration 
• For HCT patients, evidence of Grade >2 acute graft versus host disease (aGVHD); and for 
SOT patients, any history or evidence of aGVHD at Screening  
• Significant hypoxemia (ie, oxygen saturation <90% while breathing ambient air at rest)   
• Requirement for continuous infusions of inotropes or vasopressors for blood pressure support 
• Systolic blood pressure <90 mmHg, except for patients with normal resting SBP <90 mmHg 
confirmed by investigator  
• Requirement for mechanical ventilation or noninvasive ventilation 
• Resting respiratory rate ≥30 breaths/min  
• Evidence of encephalopathy or confusion 
• For HCT or non-lung SOT recipients, chest X-ray and/or CT scan with multifocal 
consolidation or diffuse alveolar consolidation. For lung transplant recipients, any new 
abnormalities on a chest X-ray and/or CT scan, other than patchy atelectasis, hyperinflation, 
and/or bronchial wall thickening, caused by LRTI.     
Reference Protocol Section 4 for detailed inclusion and exclusion criteria. 
STUDY DESIGN AND DURATION: 
This is a Phase 1/2, double-blind, placebo-controlled, dose escalation and expansion study to 
assess the safety and dose selection of ALVR106 in addition to standard of care for the treatment 
of high-risk patients with respiratory tract infections (RTIs) and clinical manifestations caused by 
RSV, IFV, hMPV, and/or PIV following HCT or SOT. This study will be conducted in 2 parts:  

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• Part A: Dose Escalation  
• Part B: Recommended Phase 2 Dose Cohort Expansion 
Throughout the study, all patients may receive standard of care as determined by the Investigator 
(or designee). Reference Protocol Section 5.7 for additional information on concomitant 
medications. 
The specific ALVR106 drug product for infusion selected for each participant will be determined 
by an electronic software system (CytoMatch™) based on 
 
. 
Reference the JUDI Manual for additional details.  
An independent Safety Review Committee (SRC) will be convened for this study to routinely 
monitor safety in a blinded fashion, unless the SRC makes a specific request for individual patient 
unblinding. Further details can be found in the SRC Charter. 
Part A (Dose Escalation) 
Part A will include up to 4 cohorts, with 4 high-risk adult patients per cohort (potentially 
expanding to 8 patients per cohort), randomized in a
ratio to ALVR106 or placebo in a -double-
blind fashion. Patients in each cohort will receive an infusion of ALVR106 cells or placebo on 
Day 1 and will return to the clinical site for assessment on Days 3, 7, 10, and 14 or more frequently 
as determined by the patient’s clinical condition at the discretion of the Investigator and in 
collaboration with the Medical Monitor.  
Patients who have not fully recovered should receive a second dose of blinded study treatment 
approximately 14 days following the first dose (reference DOSAGE FORMS AND ROUTE OF 
ADMINISTRATION below or Protocol Section 5.6.3 for additional administration information). 
Follow-up visits will occur at Day 28 (Week 4), Day 60 (Week 8), Day 180 (Month 6), and 
Day 365 (Month 12) following the patient’s first study treatment infusion. All patients will follow 
the same schedule of follow-up visits, including any patients who receive a partial infusion (less 
than the recommended dose for the patient). 
The planned doses for Cohorts 1 through 4 are presented below. Intra-patient dose escalation is 
not permitted. Reference Protocol Section 5.1 for Table on weight range dose to be administered. 
  
Planned Doses for Cohorts 1 Through 4 
Dose Cohort 
ALVR106 Dose Level 
1 
  
2 
 
3 
 
4 
 
In the event of toxicity at a planned dose, the doses may be de-escalated, based on 
recommendations from the SRC, to an interpolated intermediate dose from the planned cohorts as 
presented below. 
 

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Intermediate Doses  
Dose Cohort 
ALVR106 Dose Level 
Toxicity adjusted dose 
between Dose Cohort 1 
and 2 
)  
Toxicity adjusted dose 
between Dose Cohort 2 
and 3 
 
For each dosing cohort in Part A, the SRC will review the safety and available efficacy data after 
the first two patients have completed at least 7 days of safety monitoring following the initial dose. 
No additional patients will be dosed until that review is completed. Once review of the first two 
patients is complete (and the SRC has endorsed continuation of the study) the study enrollment of 
the remaining patients in the cohort will continue. 
At least one week after the last patient’s first dose in each cohort, the SRC will convene to assess 
blinded safety data from the current cohort and, if applicable, previous cohorts. This will allow 
for a consolidated safety review, with patients within the cohort averaging at least 14 days post 
the last dose. 
Dose escalation will proceed to identify the maximum tolerated dose (MTD) within the planned 
dose range and a recommended Phase 2 dose (RP2D) that may be the MTD or a lower dose within 
the tested dose range.  
Based on routine safety reviews, the SRC may recommend escalating the dose as planned, 
recommend an intermediate dose, recommend expansion of the current cohort, recommend 
stopping dose escalation (Part A), or stop the study. In the event of cohort expansion, up to 
4 additional patients may be enrolled and randomized in a 
 ratio to ALVR106 or placebo. In 
addition, the SRC will make a recommendation for the RP2D and starting enrollment of Part B. 
The Sponsor will determine the final RP2D based on SRC recommendation and after review of 
all available relevant safety and available efficacy data through at least Day 28 following the first 
ALVR106 or placebo infusion. Reference the SRC Charter for additional information.  
Part B (Recommended Phase 2 Dose Cohort Expansion) 
Following the determination of the RP2D in Part A, based on review of relevant safety and 
efficacy data, approximately 45 high-risk adult patients with URTIs will be randomized in a 
 
ratio to ALVR106 or placebo in a double-blind fashion.  
Patients in the ALVR106 group will receive an infusion of the RP2D as determined in Part A. 
Patients will receive an infusion of ALVR106 cells or placebo on Day 1 and will return to the 
clinical site for assessment on Days 3, 7, 10, and 14.  
Patients who have not fully recovered should receive a second dose of blinded study treatment 
approximately 
 following the first dose (reference DOSAGE FORMS AND ROUTE OF 
ADMINISTRATION below or Protocol Section 5.6.3 for additional administration information). 
Additional follow-up visits will occur at Day 28 (Week 4), Day 60 (Week 8), Day 90 (Month 3), 
Day 180 (Month 6), and Day 365 (Month 12). All patients will follow the same schedule of 
follow-up visits, including any patients who receive a partial infusion (less than the recommended 
dose for the patient). 

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The SRC will continue to routinely monitor safety in the expansion cohort. Further details can be 
found in the SRC Charter.  
During the study, the severity of adverse events will be graded by the Investigator according to 
the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 
v5.0. All hospitalizations, intensive care unit (ICU) admissions and SAEs will be reported and 
will be assessed as to whether they were caused by the RTI.   
Changes in patient reported respiratory status will be captured in the patient reported respiratory 
clinical symptoms form (reference Appendix D) and not as adverse events. A new diagnosis of 
lower respiratory tract infection (LRTI) will be captured as an AE. Any respiratory events that 
meet SAE criteria will be captured as both AEs and SAEs. Respiratory status with imaging will 
be assessed by the investigator and graded using the Radiation Therapy Oncology Group Lung 
Toxicity Scale presented below.  
Radiation Therapy Oncology Group Lung Toxicity Scale 
Organ 
Tissue 
0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Lung 
None 
Asymptomatic 
or mild 
symptoms (dry 
cough) 
Slight 
radiographic 
appearances 
Moderate 
symptomatic 
fibrosis or 
pneumonitis 
(severe cough) 
Low grade fever 
Patchy 
radiographic 
appearances 
Severe 
symptomatic 
fibrosis or 
pneumonitis 
Dense 
radiographic 
changes 
Severe 
respiratory 
insufficiency/ 
Continuous 
oxygen/ 
Assisted 
ventilation 
 
Dose-Limiting Toxicity 
DLTs are defined as treatment-related Grade ≥3 SAEs and/or Grade >3 adverse event of special 
interest (AESI) that emerge or worsen during the study. Treatment-related AE are those that occur 
after the administration of study drug and cannot be reasonably attributed to the patient’s 
underlying disease, other medical condition, or concomitant medications. 
For this study, AESI include the following as reported by the Investigator: 
• New (HCT and SOT patients) or worsening (HCT patients) of acute or chronic GVHD  
• Graft failure or rejection 
• Cytokine release syndrome (for the CRS grading scale, see Appendix C) 
• Infusion related reactions (IRRs) 
• New or worsening interstitial pneumonitis as reported by the Investigator from review of 
radiologic findings  
• Progressive dyspnea   
Focusing on AESI will provide further assurance that emergent safety issues are identified 
promptly. The AESI for this study, noted above, were selected based on the need to identify 
potential worsening in the underlying disease being targeted, as well as theoretical complications 

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of virus-specific T cells (VSTs). 
Stopping Rules 
Stopping rules in Parts A and B are defined as: 
• A patient with a DLT that is a Grade ≥3 SAE or considered a Grade ≥3 AESI that emerges 
or worsens during the study period following the patient’s initial dose and cannot be 
reasonably attributed to the patient’s underlying disease, other medical condition, or 
concomitant medications.  The study enrollment would pause to allow time for a safety 
review by the SRC. 
Focusing on AESI will provide further assurance that emergent safety issues are identified 
promptly. The AESI for this study, noted above, were selected based on the need to identify 
potential worsening in the underlying disease being targeted, as well as theoretical complications 
of virus-specific T cells (VSTs). 
The SRC will consist of an external chair and two additional independent experts in the field, at 
least one of the members will be a transplant physician and at least one member will be an 
infectious disease expert.  
The SRC will meet at least every 2 weeks to review emerging safety data and will conduct both 
open and closed meetings. Should any safety issues require review by the SRC, an emergency 
meeting will be scheduled within 72 hours. Should a death occur in the study that is considered to 
be definitely or probably related to the study product by the Investigator, the SRC will meet on an 
urgent basis, within 72 hours, to review the data available and make an assessment. Further dosing 
will be stopped until the SRC makes an assessment.  
The SRC will also convene following any Grade 4 or 5 SAE, irrespective of relatedness, or a 
Grade ≥3 SAE that may possibly, probably, or definitely be related to study treatment. 
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
For detailed instructions on ALVR106 or matching placebo administration reference the Cell 
Therapy Manual. For additional dose administration information reference Protocol Section 5.1.  
All eligible participants will be randomized to receive: 
ALVR106 cells or matching placebo administered IV over approximately 
minutes as a slow 
push on Day 1 and 
 if applicable. 
Administration of the 
 dose will be based on 
 visit assessments, as follows: 
• Patients who have demonstrated an initial objective clinical response, and a decrease in 
viral load defined by at least 50% reduction of viral load in nasal swab, will receive a 
 with the first cell line (or second dose of placebo) as initially administered, if 
available.   
• Patients who have not demonstrated either clinical improvement or decrease in viral load 
in nasal swab following the first dose will receive a new partially HLA-matched drug 
product from a different donor or placebo, if available.  If another partially HLA-matched 
drug product is not available, they will receive the same initial partially HLA-matched 
drug product or placebo.  

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• Patients who have fully recovered will not receive a second dose. Full recovery is defined 
as undetectable viral load in nasal swab by qPCR post first study treatment infusion, 
absence of respiratory symptoms, and, as applicable, normalization of imaging. 
• Patients who have experienced new onset of systemic GVHD (HCT and SOT patients), a 
Grade ≥3 worsening of GVHD (HCT patients) or Grade ≥3 infusion related reaction will 
not receive a second dose.  
Premedication can be administered to any participant at the investigator’s discretion but is not 
required, except for patients with a prior history of reaction to blood products (reference Section 
5.7.2 for premedication options).    
EFFICACY VARIABLES:  
Primary Efficacy Endpoint 
The primary efficacy endpoints include the following: 
• The reduction in viral load from nasal swab specimens from pre-dose through Day 28. Time-
weighted average change from baseline to Day 28 in log10 viral load will be measured by 
qPCR (based on the central laboratory) for Part A. 
• Proportion of patients with ≥50% reduction in viral load from nasal swab specimens and 
improvement in clinical signs and symptoms through Day 28 following the patient’s first 
ALVR106 infusion for Part B. 
Reference Protocol Section 6.1 for efficacy endpoints. 
SAFETY VARIABLES: 
The safety endpoints include the incidence of the following AESI as reported by the Investigator: 
• New (HCT and SOT patients) or worsening (HCT patients) of acute or chronic 
GVHD  
• Graft failure or rejection 
• Cytokine release syndrome (for the CRS grading scale, see Appendix C) 
• Infusion related reactions (IRRs) 
• New or worsening interstitial pneumonitis as reported by the Investigator from 
review of radiologic findings  
• Progressive dyspnea   
Safety assessments also include treatment-emergent adverse events (TEAEs); infusion site 
reactions; clinical laboratory assessments; changes in corticosteroid dosage; and abnormalities in 
vital signs or physical examination findings (including heart and lung auscultation, skin, and 
ears/nose/throat). Treatment-emergent is defined as adverse events from the first dose of study 
drug to the last dose of study drug plus 12 weeks.  
Reference Protocol Section 7.1 for safety endpoints. 
STATISTICAL ANALYSES: 

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A Statistical Analysis Plan (SAP) will be finalized before database lock. Any changes to the 
methods described in the final SAP will be described and justified as needed in the Clinical Study 
Report. 
Data from Part A and Part B of the study will be summarized and analyzed separately.  All the 
safety and efficacy endpoints will be summarized using descriptive statistics by treatment group. 
Categorical data will generally be summarized with counts and percentages of patients. 
Continuous data will generally be summarized with descriptive statistics, including the number of 
non-missing values, mean, median, standard deviation, minimum, and maximum. 
 
Treatment-emergent adverse events will be summarized by System Organ Class and Preferred 
Term and further by severity (according to the NCI CTCAE v5.0) and relationship to study 
treatment. The incidence of AESI and the corresponding 95% exact binomial confidence 
intervals will be presented by treatment group. Descriptive statistics will be provided for 
relevant laboratory and vital sign data.  
The SRC will review the cumulative safety and available efficacy data from each previous cohorts 
to recommend dose level and regimen for the subsequent cohorts. 
SAMPLE SIZE DETERMINATION: 
No formal sample size determination was performed due to the exploratory nature of this study. 
The sample size has been set for an initial assessment of the safety and antiviral activity of 
ALVR106. 
For the Part A dose escalation portion of the study, approximately 16 to 32 patients will be 
randomized. The actual number of patients randomized will depend on the safety profile for each 
cohort and when the MTD is reached. 
For Part B, the RP2D cohort expansion, a total of approximately 45 patients will be randomized.  
SITES:  Approximately 45 sites 
SPONSOR: 
AlloVir 
Kirby Grove 
2925 Richmond Avenue, Suite 1200 
Houston, TX 77098 
United States 
Telephone: 936-662-3626 
Fax: 979-289-7437 
 

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SCHEDULE OF PROCEDURES – PART A 
Schedule of Procedures – Part A (Dose Escalation)  
Study Week/Month 
Weeks 
-
 
 
 
 
  
  
 
  
] 
Study Day 
-
  
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±2 
±3 
±5 
±5 
±28 
±28 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
I/E criteria 
X 
X [1] 
 
 
 
 
 
 
 
 
Demographics and medical 
history [2] 
X 
 
 
 
 
 
 
 
 
 
HLA match and/or typing for 
drug product selection  
X 
 
 
 
 
 
 
 
 
 
Randomization [3] 
 
X 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hospital information [4] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination [5] 
X 
X  
X 
X 
X 
X 
X 
 
 
 
Height and weight [7] 
X 
X 
 
 
 
 
 
 
 
 
Vital signs including SpO2 [8] 
X 
X 
X 
X 
X 
X 
X 
 
 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
Chest X-ray and/or CT scan [9] 
X 
 
 
 
X  
 
X 
 
 
 
Clinical laboratories (CBC with 
differential, chemistry, LFTs 
[10]) 
X 
X 
 
 
 
X 
X 
 
 
 
Urinalysis 
X 
X 
 
 
 
 
X 
 
 
 
RSV, IFV, hMPV, and PIV viral 
load measured [11] 
X 
X  
X 
X 
X 
 
X 
X 
X 
 

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Study Week/Month 
Weeks 
 
 
 
 
  
  
 
  
 
Study Day 
  
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±2 
±3 
±5 
±5 
±28 
±28 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
Blood sample for viremia 
assessment (stored for possible 
analysis) 
X 
X  
 
X 
 
X 
X 
X 
X 
 
SARS-CoV-2 assessment  
X 
 
 
 
 
 
 
 
 
 
Pregnancy test [12] 
X 
X 
 
 
 
X 
 
 
X 
 
Donor-specific antibody sample 
(SOT only) 
 
X 
 
 
 
 
 
X 
 
 
Bank PBMCs for virus-specific 
immunity and plasma for 
cytokine evaluation [13] 
 
X 
 
 
 
X 
X 
X 
X 
 
Patient (or caretaker)-reported 
respiratory clinical 
signs/symptoms [14] 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Investigator assessment of 
respiratory status and, if 
applicable, may include 
assessment of spirometry [15] 
X 
X 
X 
X 
X 
X 
X 
 
X [15] 
X [15] 
Acute GVHD evaluation [16] 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Chronic GVHD evaluation [16] 
 
X 
 
 
 
 
X 
X 
X 
X 
Study treatment administration 
[17] 
 
X 
 
 
 
X 
 
 
 
 
Infusion site evaluation [18] 
 
X 
X 
X 
X 
X 
X 
 
 
 
Post-infusion monitoring [19] 
 
X  
 
 
 
X  
 
 
 
 
Health Status (Survival) 
 
 
 
 
 
 
 
 
 
X 
Note: Patients 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. 
Patient eligibility must be reconfirmed prior to study treatment administration. See Section 4.3. 
2. 
Medical history will include diagnosis of underlying disease requiring transplant, underlying disease state at the time of RTI diagnosis, type of donor and cell source of the HCT 
received (HCT participants only), type of SOT, date of transplant, conditioning regimen, CMV serostatus, presence of GVHD, and smoking status. 
3. 
Randomization will occur after all screening procedures are complete and prior to study treatment administration. 

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4. 
Includes information on hospital admission and discharge, ICU transfer, oxygen supplementation, and mechanical or noninvasive ventilation. 
5. 
A complete physical examination will be performed at screening and Baseline/Day 1. Abbreviated physical examinations will be performed at all subsequent visits. 
6. 
On Day 1, all assessments should be performed before dosing, except treatment administration, infusion site evaluation and post-infusion monitoring 
7. 
Height should be collected at screening only. The patient’s screening weight will be used to calculate the 1st and 2nd doses and the dose will remain the same for both infusions.  
8. 
Vital signs include body temperature, heart rate, respiratory rate, SpO2, and systolic and diastolic blood pressure. Vital signs will be collected after the patient has rested for at 
least 5 minutes in the supine position. 
9. 
All patients will have screening imaging performed and analyzed locally as long as the imaging can be transmitted to the central reader. Imaging will be repeated at Days 10 
and 28 for all patients, and as needed in cases of suspected progression to LRTI. Patient management will be based on the local reading, but the final analysis of radiologic 
progression will be based on the central reader’s assessment.  
10. LFTs will include alkaline phosphatase, total and direct bilirubin, AST, and ALT. 
11. Confirmation of RTI associated with the 4 target viruses will be done through a nasal swab. Local laboratory results obtained within 3 days of Screening or during the screening 
period will be acceptable for eligibility determination. However, a central nasal swab sample must be collected and submitted to the central laboratory prior to dosing. Nasal 
swabs for Screening and Baseline should also be analyzed for SARS-CoV-2. All eligible participants will have a nasal swab collected at Baseline and post-treatment visits and 
sent to Central Laboratory for analysis. Samples will be stored for potential future viral genotypic or viral load analysis.   
12. 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 and Day 
14 for females of childbearing potential, only if the pregnancy test performed at screening was not completed within 48 hours prior to study treatment administration. These 
tests may be performed at the local laboratory. 
13. Day 1 blood will be collected predose. Blood will be collected into a cell separation tube and processed to generate a PBMC fraction and a plasma fraction. Plasma should be 
aliquoted into two samples and frozen for potential future evaluation. PBMC should be aliquoted into at least 2 aliquots or at 5x106 cells/vial.  
14. The patient will complete the electronic respiratory clinical signs questionnaire (see Appendix D) 
15. The Investigator will assess patient’s respiratory status and complete the Respiratory Tract Infection Status eCRF in EDC at each visit through Week 4 post-initial infusion for 
all patients. For lung transplant recipients, the Investigator will complete additional assessments at Month 6 and 12 post-initial infusion. For lung transplant recipients, if required 
by the investigator to support assessment of respiratory status, a spirometry assessment may be completed by the patient at Baseline, Week 4, Months 6 and 12. Spirometry 
should be collected in line with local standard clinical practice. Reference P-106-001 eCRF Completion Guidelines for additional information.    
16. If any patient develops GVHD, that patient may receive standard GVHD treatment at the discretion of the Investigator. Staging and grading of acute GVHD will be reported 
using MAGIC guidelines; for HCT patients, response to treatment will be assessed as per CIBMTR modifications to the CIBMTR response index. For HCT patients, 
manifestations of chronic GVHD and response to treatment will be assessed as per National Institutes of Health consensus guidelines for chronic GVHD. 
17. Patients randomized to the ALVR106 group will receive ALVR106 cells or placebo as an infusion (administered IV over approximately  minutes as a slow push). Based on 
treatment response on Day
patients may receive a 
 dose of blinded study treatment approximately 
 following the first dose.  
18. Includes pain, tenderness, erythema, swelling, and induration. On infusion days, performed pre-dose and at 1 hour post-dose. 
19. Patients will be monitored closely and must remain in the clinic for 1 hour after the end of each infusion. Vital signs and pulse oximetry will be measured at the end of the 
infusion (+/- 5 minutes), and at 15 minutes (+/- 5 minutes), 30 minutes (+/- 10 minutes), 45 minutes (+/- 15 minutes), and 60 minutes (+/- 15 minutes) after the end of the 
infusion. Post-infusion monitoring should be completed for all infusions of study treatment. 
20. Patients who discontinue the study before the Month 12 visit should complete all assessments in the Month 12/Early Termination visit either in clinic or virtually via phone or 
telemedicine. At a minimum a follow-up should occur within 2 weeks of the last study dose.  
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; CIBMTR = Center for International Blood and Marrow Transplant Research; 
CMV = cytomegalovirus; COA = clinical outcome assessment; CT = computed tomography; DNA = deoxyribonucleic acid; ECG = electrocardiogram; ET = Early Termination;; 
GVHD = graft versus host disease; HCT = hematopoietic cell transplant; HLA = human leukocyte antigen; hMPV = human metapneumovirus; ICU = intensive care unit; 
I/E = inclusion and exclusion; IV = intravenous(ly); LFT = liver function test; LRTI = lower respiratory tract infection; MAGIC = Mount Sinai Acute GVHD International 
Consortium; NA = not applicable; PBMC = peripheral blood mononuclear cell; PIV = parainfluenza virus;; qPCR = quantitative polymerase chain reaction; RSV = respiratory 
syncytial virus; RTI = respiratory tract infection; SOT=Solid Organ Transplant; SpO2 = peripheral capillary oxygen saturation; URTI = upper respiratory tract infection; VC = vital 
capacity; VST = virus-specific T cell. 

 
 
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SCHEDULE OF PROCEDURES – PART B 
Schedule of Procedures – Part B (RP2D Cohort Expansion) 
Study Week/Month 
Weeks -
2
 
 
 
 
 
 
 
 
 
 
Study Day 
-10 
  
 
 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±2 
±3 
±5 
±5 
±28 
±28 
±28 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
I/E criteria 
X 
X 
[1] 
 
 
 
 
 
 
 
 
 
Demographics and medical 
history [2] 
X 
 
 
 
 
 
 
 
 
 
 
HLA match and/or typing for 
drug product selection 
X 
 
 
 
 
 
 
 
 
 
 
Randomization [3] 
 
X 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hospital information [4] 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination [5] 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
 
Height and weight [7] 
X 
X 
 
 
 
 
 
 
 
X 
 
Vital signs including SpO2 [8] 
X 
X  
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG 
X 
 
 
 
 
 
 
 
 
 
 
Chest X-ray and/or CT scan 
[9] 
X 
 
 
 
X 
 
X 
 
 
 
 
Clinical laboratories (CBC 
with differential, chemistry, 
LFTs [10]) 
X 
X 
 
 
 
X 
X 
X 
 
X 
 
Urinalysis 
X 
X 
 
 
 
 
X 
 
 
X 
 

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Study Week/Month 
 
 
 
 
 
 
 
 
 
 
Study Day 
 
  
 
 
 
 
 
 
 
 
 
 
 
Visit Window (Days) 
NA 
NA 
±2 
±2 
±2 
±3 
±5 
±5 
±28 
±28 
±28 
Study Procedures 
 
 
 
 
 
 
 
 
 
 
 
RSV, IFV, hMPV, and PIV 
viral load measured [11] 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
Blood sample for viremia 
assessment (stored for possible 
analysis) 
X 
X 
 
X 
 
X 
X 
X 
 
X 
 
SARS-CoV-2 assessment  
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy test [12] 
X 
X 
 
 
 
X 
 
 
 
X 
 
Donor specific antibody 
sample (SOT only) 
 
X 
 
 
 
 
 
 
X 
 
 
Bank PBMCs for virus-specific 
immunity and plasma for 
cytokine evaluation [13] 
 
X 
 
 
 
X 
X 
X 
X 
X 
 
Patient (or caretaker)-
reported respiratory clinical 
signs/symptoms [14] 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Investigator assessment of 
respiratory status and, if 
applicable, may include 
assessment of spirometry [15] 
X 
X 
X 
X 
X 
X 
X 
 
 
X [15] 
X [15] 
Acute GVHD evaluation [16] 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Chronic GVHD 
evaluation [16] 
 
X 
 
 
 
 
X 
X 
 
X 
X 
Study treatment 
administration [17] 
 
X 
 
 
 
X 
 
 
 
 
 
Infusion site evaluation [18] 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
Post-infusion monitoring [19] 
 
X  
 
 
 
X 
 
 
 
 
 
Health Status (Survival) 
 
 
 
 
 
 
 
 
 
 
X 

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Note: Patients 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. 
Patient eligibility must be reconfirmed prior to study treatment administration. See Section 4.3. 
2. 
Medical history will include diagnosis of underlying disease requiring transplant, underlying disease state at the time of RTI diagnosis, type of donor and cell source of the HCT 
received (HCT participants only), type of SOT, date of transplant, conditioning regimen, CMV serostatus, presence of GVHD, and smoking status. 
3. 
Randomization will occur after all screening procedures are complete and prior to study treatment administration. 
4. 
Includes information on hospital admission and discharge, ICU transfer, oxygen supplementation, and ventilation. 
5. 
A complete physical examination will be performed at screening and Baseline/Day 1. Abbreviated physical examinations will be performed at all subsequent visits. 
6. 
On Day 1, all assessments should be performed before dosing, except treatment administration, infusion site evaluation and post-infusion monitoring 
7. 
Height should be collected at Screening only. The patient’s screening weight will be used to calculate the 1st and 2nd doses and the dose will remain the same for both infusions. 
8. 
Vital signs include body temperature, heart rate, respiratory rate, SpO2, and systolic and diastolic blood pressure. Vital signs will be collected after the patient has rested for at 
least 5 minutes in the supine position. 
9. 
All patients will have screening imaging performed and analyzed locally as long as the imaging can be transmitted to the central reader. Imaging will be repeated at Days 10 
and 28 for all patients, and as needed in cases of suspected progression to LRTI. Patient management will be based on the local reading, but the final analysis of radiologic 
progression will be based on the central reader’s assessment.  
10. LFTs will include alkaline phosphatase, total and direct bilirubin, AST, and ALT. 
11. Confirmation of RTI associated with the 4 target viruses will be done through a nasal swab. Local laboratory results obtained within 3 days of Screening or during the screening 
period will be acceptable for eligibility determination. However, a central nasal swab sample must be collected and submitted to the central laboratory prior to dosing. Nasal 
swabs for Screening and Baseline should also be analyzed for SARS-CoV-2. All eligible participants will have a nasal swab collected at Baseline and post-treatment visits and 
sent to Central Laboratory for analysis. Samples will be stored for potential future viral genotypic or viral load analysis.   
12. 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 and Day 
14 for females of childbearing potential, only if the pregnancy test performed at screening was not completed within 48 hours prior to study treatment administration. These 
tests may be performed at the local laboratory 
13. Day 1 blood will be collected predose. Blood will be collected into a cell separation tube and processed to generate a PBMC fraction and a plasma fraction. Plasma should be 
aliquoted into two samples and frozen for potential future evaluation. PBMC should be aliquoted into at least 2 aliquots or at 5x106 cells/vial.  
14. The patient will complete the electronic respiratory clinical signs questionnaire (see Appendix D). 
15. The Investigator will assess patient’s respiratory status and complete the Respiratory Tract Infection Status eCRF in EDC at each visit through Week 4 post-initial infusion for 
all patients. For lung transplant recipients, the Investigator will complete additional assessments at Month 6 and 12 post-initial infusion. For lung transplant recipients, if required 
by the investigator to support assessment of respiratory status, a spirometry assessment may be completed by the patient at Baseline, Week 4, Months 6 and 12. Spirometry 
should be collected in line with local standard clinical practice. Reference P-106-001 eCRF Completion Guidelines for additional information. 
16. If any patient develops GVHD, that patient may receive standard GVHD treatment at the discretion of the Investigator. Staging and grading of acute GVHD will be reported 
using MAGIC guidelines; for HCT patients, response to treatment will be assessed as per CIBMTR modifications to the CIBMTR response index. For HCT patients, 
manifestations of chronic GVHD and response to treatment will be assessed as per National Institutes of Health consensus guidelines for chronic GVHD. 
17. Patients randomized to the ALVR106 group will receive ALVR106 cells or placebo as an infusion (administered IV over approximately  minutes as a slow push). Based on 
treatment response on Day
 patients may receive a
 dose of blinded study treatment approximately 
 following the first dose.  
18. Includes pain, tenderness, erythema, swelling, and induration. On infusion days, performed pre-dose and at 1 hour post-dose. 
19. Patients will be monitored closely and must remain in the clinic for 1 hour after the end of each infusion. Vital signs and pulse oximetry will be measured at the end of the 
infusion (+/- 5 minutes), and at 15 minutes (+/- 5 minutes), 30 minutes (+/- 10 minutes), 45 minutes (+/- 15 minutes), and 60 minutes (+/- 15 minutes) after the end of the 
infusion. Post-infusion monitoring should be completed for all infusions of study treatment. 
20. Patients who discontinue the study before the Month 12 visit should complete all assessments in the Month 12/Early Termination visit either in clinic or virtually via phone or 
telemedicine. At a minimum a follow-up should occur within 2 weeks of the last study dose.  
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; CIBMTR = Center for International Blood and Marrow Transplant Research; 
CMV = cytomegalovirus; COA = clinical outcome assessment; CT = computed tomography; ECG = electrocardiogram; ET = Early Termination; GVHD = graft versus host disease; 
HCT = hematopoietic cell transplant; HLA = human leukocyte antigen; hMPV = human metapneumovirus; ICU = intensive care unit; I/E = inclusion and exclusion; 
IV = intravenous(ly); LFT = liver function test; LRTI = lower respiratory tract infection; MAGIC = Mount Sinai Acute GVHD International Consortium; NA = not applicable; 

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PBMC = peripheral blood mononuclear cell; PIV = parainfluenza virus; qPCR = quantitative polymerase chain reaction; RP2D = recommended Phase 2 dose; RSV = respiratory 
syncytial virus; SOT=Solid Organ Transplant; SpO2 = peripheral capillary oxygen saturation; URTI = upper respiratory tract infection; VC = vital capacity; VST = virus-specific T 
cell. 
 

 
 
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TABLE OF CONTENTS 
Investigator Agreement ................................................................................................................... 2 
Synopsis .......................................................................................................................................... 3 
Schedule of Procedures – Part A .................................................................................................. 11 
Schedule of Procedures – Part B ................................................................................................... 14 
Table of Contents .......................................................................................................................... 18 
List of Tables ................................................................................................................................ 22 
List of Figures ............................................................................................................................... 22 
List of Abbreviations and Definition of Terms............................................................................. 23 
1 Introduction and Background Information ............................................................................. 25 
1.1 
Viral Infection Following Transplant ............................................................................ 25 
1.2 
Adoptive Immunotherapy for Viral Infections Following Hematopoietic Cell 
Transplant ...................................................................................................................... 25 
1.3 
Adoptive Immunotherapy for Viral Infections Following Solid Organ Transplant ...... 26 
1.4 
ALVR106 ...................................................................................................................... 26 
1.4.1 Overview of Nonclinical Studies ...................................................................... 27 
1.5 
Overview of Clinical Experience with Similar VST Platforms to ALVR106 .............. 27 
1.5.1 ALVR109: VST in the Treatment of COVID-19 Lower Respiratory Tract 
Infection ............................................................................................................ 27 
1.5.2 Posoleucel (ALVR105): VST in the Treatment of Viral Infection in HCT 
Patients 28 
1.5.3 Posoleucel: VSTs in the Treatment of Viral Infection in SOT Patients ............ 29 
1.6 
Rationale ........................................................................................................................ 30 
1.7 
Risk/Benefit ................................................................................................................... 31 
1.7.1 Potential Risks ................................................................................................... 31 
1.7.2 Potential Benefits .............................................................................................. 32 
2 Study Objectives ..................................................................................................................... 33 
2.1 
Part A (Dose Escalation) ............................................................................................... 33 
2.1.1 Primary Objective ............................................................................................. 33 
2.1.2 Secondary Objectives ........................................................................................ 33 
2.1.3 Exploratory Objectives ...................................................................................... 33 
2.2 
Part B (Recommended Phase 2 Dose Cohort Expansion) ............................................. 34 

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2.2.1 Primary Objective ............................................................................................. 34 
2.2.2 Secondary Objectives ........................................................................................ 34 
2.2.3 Exploratory Objectives ...................................................................................... 34 
3 Study Description.................................................................................................................... 36 
3.1 
Summary of Study Design ............................................................................................ 36 
3.1.1 Part A (Dose Escalation) ................................................................................... 37 
3.1.2 Part B (Recommended Phase 2 Dose Cohort Expansion) ................................. 39 
3.2 
Dose-Limiting Toxicity ................................................................................................. 39 
3.3 
Stopping Rules .............................................................................................................. 39 
4 Selection and Withdrawal of Patients ..................................................................................... 41 
4.1 
Inclusion Criteria ........................................................................................................... 41 
4.2 
Exclusion Criteria .......................................................................................................... 42 
4.3 
Eligibility Confirmation ................................................................................................ 43 
4.4 
Withdrawal Criteria ....................................................................................................... 44 
4.5 
Screen Failures .............................................................................................................. 44 
5 Study Treatments .................................................................................................................... 45 
5.1 
Treatment Groups .......................................................................................................... 45 
5.2 
Cohort Progression and Dose Escalation ...................................................................... 46 
5.3 
Rationale for Dosing ..................................................................................................... 46 
5.4 
Randomization and Blinding ......................................................................................... 46 
5.5 
Breaking the Blind at Investigational Sites ................................................................... 47 
5.6 
Drug Supplies ................................................................................................................ 47 
5.6.1 Formulation and Packaging ............................................................................... 47 
5.6.2 Study Treatment Preparation and Dispensing ................................................... 47 
5.6.3 Study Treatment Administration ....................................................................... 47 
5.6.4 Treatment Compliance ...................................................................................... 48 
5.6.5 Storage and Accountability ............................................................................... 48 
5.7 
Prior and Concomitant Medications and/or Procedures ................................................ 49 
5.7.1 Excluded Medications and/or Procedures ......................................................... 49 
5.7.2 Permitted Medications and/or Procedures ......................................................... 49 
5.7.3 Documentation of Prior and Concomitant Medication Use .............................. 50 
6 Efficacy Assessments.............................................................................................................. 51 

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6.1 
Efficacy Endpoints ........................................................................................................ 51 
6.2 
Viral Load Assessment .................................................................................................. 52 
6.3 
Imaging .......................................................................................................................... 52 
6.4 
Reconstitution of Antiviral Immunity ........................................................................... 52 
6.5 
Respiratory Clinical Signs/Symptoms .......................................................................... 52 
7 Safety Assessments ................................................................................................................. 54 
7.1 
Safety Endpoints ........................................................................................................... 54 
7.2 
Adverse Events .............................................................................................................. 54 
7.2.1 Adverse (Drug) Reaction .................................................................................. 55 
7.2.2 Unexpected Adverse Drug Reaction ................................................................. 55 
7.2.3 Assessment of Adverse Events by the Investigator .......................................... 55 
7.2.4 Adverse Events of Special Interest .................................................................... 57 
7.3 
Serious Adverse Events ................................................................................................. 57 
7.4 
Serious Adverse Event Reporting – Procedures for Investigators ................................ 58 
7.5 
Pregnancy Reporting ..................................................................................................... 58 
7.6 
Expedited Reporting ...................................................................................................... 59 
7.7 
Special Situation Reports .............................................................................................. 59 
7.8 
Clinical Laboratory Evaluations .................................................................................... 60 
7.9 
Vital Signs ..................................................................................................................... 61 
7.10 Electrocardiograms ........................................................................................................ 61 
7.11 Physical Examinations .................................................................................................. 61 
7.12 Graft Versus Host Disease ............................................................................................ 61 
7.12.1 Acute Graft Versus Host Disease ...................................................................... 61 
7.12.2 Chronic Graft Versus Host Disease (HCT Only) .............................................. 62 
7.13 Infusion Site Evaluation ................................................................................................ 62 
7.14 Post-Infusion Monitoring .............................................................................................. 62 
8 StatisticAL Consideration ....................................................................................................... 63 
8.1 
Analysis Populations ..................................................................................................... 63 
8.1.1 Intent-to-Treat Population ................................................................................. 63 
8.1.2 Safety Population .............................................................................................. 63 
8.2 
Statistical Methods ........................................................................................................ 63 
8.2.1 Analysis of Efficacy Endpoints ......................................................................... 63 

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8.2.2 Analysis of Safety Endpoints ............................................................................ 63 
8.2.3 Interim Analysis ................................................................................................ 64 
8.2.4 Safety Review Committee ................................................................................. 64 
8.2.5 Sample Size Determination ............................................................................... 64 
9 Data Management and Record Keeping ................................................................................. 65 
9.1 
Data Management ......................................................................................................... 65 
9.1.1 Data Handling ................................................................................................... 65 
9.1.2 Computer Systems ............................................................................................. 65 
9.1.3 Data Entry ......................................................................................................... 65 
9.1.4 Medical Information Coding ............................................................................. 65 
9.1.5 Data Validation ................................................................................................. 65 
9.2 
Record Keeping ............................................................................................................. 65 
9.3 
End of Study .................................................................................................................. 66 
10 Investigator Requirements and Quality Control ..................................................................... 67 
10.1 Ethical Conduct of the Study ........................................................................................ 67 
10.2 Institutional Review Board/Independent Ethics Committee ......................................... 67 
10.2.1 Institutional Review Board ................................................................................ 67 
10.2.2 Independent Ethics Committee ......................................................................... 67 
10.3 Informed Consent .......................................................................................................... 67 
10.4 Study Monitoring Requirements ................................................................................... 68 
10.5 Disclosure of Data ......................................................................................................... 68 
10.6 Retention of Records ..................................................................................................... 68 
10.7 Publication Policy ......................................................................................................... 69 
10.8 Financial Disclosure ...................................................................................................... 69 
10.9 Insurance and Indemnity ............................................................................................... 69 
10.10 Legal Aspects ................................................................................................................ 69 
11 Study Administrative Information .......................................................................................... 70 
11.1 Protocol Amendments ................................................................................................... 70 
12 References ............................................................................................................................... 71 
Appendix A:  Clinical Laboratory Analytes ................................................................................. 75 
Appendix B:  Graft Versus Host Disease Scales .......................................................................... 76 
Appendix C:  Cytokine Release Syndrome Grading Scale and Management .............................. 79 

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Appendix D:  Patient-Reported Assessment of Respiratory Clinical Symptoms ......................... 81 
Summary of changes ..................................................................................................................... 82 
LIST OF TABLES 
Table 1. 
Radiation Therapy Oncology Group Lung Toxicity Scale ......................................... 36 
Table 2. 
Planned Doses for Cohorts 1 Through 4 ..................................................................... 38 
Table 3. 
Planned Weight-Based Doses for Cohorts 1 Through 4 ............................................. 45 
 
LIST OF FIGURES 
Figure 1. Summary of Study Design .......................................................................................... 37 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
Abbreviation 
Definition 
AdV 
Adenovirus  
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BKV 
BK virus 
CAR 
Chimeric antigen receptor 
CARV 
Community-acquired respiratory virus 
CFR 
Code of Federal Regulations 
CIBMTR 
Center for International Blood and Marrow Transplant Research 
CMV 
Cytomegalovirus  
CRA 
Clinical Research Associate 
CRS 
Cytokine release syndrome 
CT 
Computed tomography 
CTA 
Clinical trial authorization 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLI 
Donor lymphocyte infusion 
DLT 
Dose-limiting toxicity 
EBV 
Epstein-Barr virus 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EIU 
Exposure In Utero 
FDA 
Food and Drug Administration 
FEV1 
Forced expiratory volume in the first second 
FVC 
Forced vital capacity 
GCP 
Good Clinical Practice 
GVHD 
Graft versus host disease 
HCT 
Hematopoietic cell transplant 
HHV-6 
Human herpes virus-6 
HLA 
Human leukocyte antigen 
hMPV 
Human metapneumovirus 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
ICU 
Intensive Care Unit 
IFV 
Influenza virus 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 

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Abbreviation 
Definition 
IV 
Intravenous(ly) 
LRTI 
Lower respiratory tract infection 
mITT 
Modified Intent-to-Treat 
MTD 
Maximum tolerated dose 
NCI 
National Cancer Institute 
PBMC 
Peripheral blood mononuclear cell 
PIV 
Parainfluenza virus 
qPCR 
Quantitative polymerase chain reaction 
RP2D 
Recommended Phase 2 dose 
RSV 
Respiratory syncytial virus 
RTI 
Respiratory tract infection 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
sCRS 
Severe cytokine release syndrome 
SRC 
Safety Review Committee 
SOT 
Solid Organ Transplant  
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
URTI 
Upper respiratory tract infection 
VAS 
Visual analog scale 
VC 
Vital capacity 
VST 
Virus-specific T cell 
 

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1 
INTRODUCTION AND BACKGROUND INFORMATION  
1.1 
Viral Infection Following Transplant 
Respiratory infections are among the most common types of tissue-invasive infections in 
immunocompromised patients (eg, hematopoietic cell transplantation (HCT) and solid organ 
transplantation (SOT)). Community-acquired viruses such as respiratory syncytial virus (RSV), 
influenza (IFV), parainfluenza virus (PIV), and human metapneumovirus (hMPV) are global 
leading causes of morbidity and mortality during the period prior to immune recovery after HCT 
or in the setting of potent immunosuppressive regimens following HCT or SOT. 
Young children, the elderly, and patients with compromised immune systems are particularly at 
risk. Respiratory tract infections (RTIs) affect up to 40% of allogeneic HCT and up to 21% SOT 
recipients, with symptoms ranging from mild to severe.1,2,3 While initial symptoms of these viruses 
in transplant patients may be limited to the upper respiratory tract and include rhinorrhea, cough, 
and/or fever, approximately 50% of cases progress to the lower respiratory tract,4 leading to more 
severe conditions such as pneumonia, bronchiolitis, and specific to lung transplant recipients, 
bronchiolitis obliterans syndrome (BOS) or chronic lung allograft dysfunction (CLAD).4 Mortality 
rates in HCT recipients due to these conditions are as high as 23% to 50%.1 In SOT, especially 
lung transplant recipients, mortality rates due to these conditions are as high as 20%.5 
Currently, there are no approved vaccines or antiviral drugs for hMPV or PIV. For IFV, treatment 
with antiviral agents such as neuraminidase inhibitors is available, however, immunocompromised 
patients are at greater risk for developing infection with drug resistant IFV. While prophylactic 
IFV vaccines are available annually, they are not recommended for HCT and SOT patients until 
at least 3-6 months following transplant.6,7 For RSV, aerosolized ribavirin has been approved by 
the FDA for the treatment of RSV, but it is costly and difficult to administer.  
In healthy individuals, T cell immunity defends against RSV, IFV, PIV, and hMPV. In HCT and 
SOT recipients, the use of potent immunosuppressive regimens leaves patients susceptible to 
severe viral infections. There is a significant unmet need for treatment options that can address 
these common community-acquired respiratory infections in immunocompromised transplant 
patients. Cellular immunotherapy to restore viral-specific immunity has been investigated as a 
potential therapeutic option in immunocompromised patients’ post-transplant.   
1.2 
Adoptive Immunotherapy for Viral Infections Following Hematopoietic Cell 
Transplant 
The first virus to be targeted using an adoptive T cell transfer approach was cytomegalovirus 
(CMV).8 This was followed by numerous studies with not only CMV-directed T cell products 
(eg, ex vivo expanded polyclonal lines, interferon γ-captured cells, and multimer-selected 
products),9,10,11,12,13,14,15 but also T cell products directed toward other viruses, including Epstein-
Barr virus (EBV) and adenovirus (AdV). These clinically implemented immunotherapeutic 
strategies are considered safe and are associated with clinical benefit.16,17,18,19,20,21,22,23,24 
Adoptive transfer of HCT donor-derived VSTs (ie, VSTs expanded or selected from a transplant 
donor) has been successfully used to prevent and treat viral infections,25 including CMV and AdV 
infections, as well as drug-refractory EBV-positive lymphomas, that complicate HCT.26 However, 
despite the successful use of various stem cell donor-derived VSTs over more than 20 years, there 

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are significant limitations to this approach, making it unsuitable for a potential commercial 
product. 
An alternative to preparing stem cell donor-derived VSTs for individual patients is to bank 
partially human leukocyte antigen (HLA)-matched allogeneic VSTs, obtained from healthy third-
party donors (not the stem cell donor) with demonstrated immunity to virus(es), that could be 
available as an “off-the-shelf” product for immediate use. This approach theoretically overcomes 
some of the limitations of HCT donor-derived VSTs. Specifically, patients do not have to wait for 
the drug product to be produced, and, taking the multivirus approach (ie, deriving drug products 
by antigenically stimulating against peptides from multiple viruses of interest), results in a 
ready-for-use drug product specific for multiple viruses of interest. A potential concern with this 
approach is that the mismatched product may not persist long enough in vivo to control the viral 
infection, because the recipient may generate an immune response to the non-shared 
transplantation antigens. Despite this theoretical concern, several studies have demonstrated that 
third-party VSTs are associated with clinical benefit.27,28,29,30 
1.3 
Adoptive Immunotherapy for Viral Infections Following Solid Organ 
Transplant 
Adoptive transfer of donor-derived VSTs (ie, VSTs expanded or selected from a transplant donor) 
has been successfully used to treat EBV-associated post-transplant lymphoproliferative disease 
(PTLD) in SOT recipients. Haque T et al.31 conducted a phase 2 multicenter clinical trial aimed to 
test the safety and efficacy of banked allogeneic EBV-specific VSTs used on a best HLA-match 
basis to treat PTLD. Thirty-three PTLD patients who had failed on conventional therapy were 
enrolled. Transplant types were as follows: stem cell, 2; heart, 2; kidney, 13; liver, 10; liver and 
small bowel, 3; lung, 2; heart and lung, 1. The response rate (complete or partial) in 33 patients 
was 64% at 5 weeks and 52% at 6 months. Fourteen patients achieved a complete remission, 3 
showed a partial response, and 16 had no response at 6 months (5 died before completing 
treatment). The response rate in this poor prognosis patient group were encouraging. No adverse 
effects of VST infusions were observed; the infusions were well tolerated with no evidence of 
acute infusion reactions. No adverse effect on the transplanted organ or evidence of VST-host 
disease was observed. Their results demonstrated that allogeneic VSTs for the treatment of PTLD 
in SOT recipients was safe and well tolerated.  
1.4 
ALVR106 
ALVR106 is a novel, allogeneic, off-the-shelf, multi-virus specific T cell (VST) therapy for the 
treatment of respiratory infection caused by RSV, IFV, PIV, and hMPV. ALVR106 is a 
polyclonal (CD4+ and CD8+) VST product containing cells that are reactive against 4 viruses 
(RSV, IFV, PIV, and hMPV). Virus specific T cells are generated by exposing peripheral blood 
mononuclear cells (PBMCs) to peptide mixtures (pepmixes) and cytokines
, in 
culture medium followed by ex vivo expansion. 
 
 
A bank of VSTs from eligible third-party healthy, pre-screened (for infectious agents and disease 
risk factors as mandated by Food and Drug Administration [FDA] 21 Code of Federal 
Regulations [CFR] part 1271, subpart C) donors that have prior exposure to the 4 target viruses 

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(RSV, IFV, PIV, and hMPV) were generated. These donors were carefully chosen to reflect and 
accommodate the HLA diversity of the allogeneic HCT population to be enrolled in this study. 
ALVR106 is cryopreserved for use as a partially HLA-matched “off the shelf” product. 
Please reference the Investigator Brochure (IB) for additional information on ALVR106 
including: 
• Nonclinical Studies 
1.4.1 
Overview of Nonclinical Studies   
AlloVir previously demonstrated that the adoptive transfer of in vitro expanded VSTs can be safely 
administered to treat infections associated with EBV, CMV, BK virus (BKV), human 
herpesvirus-6 (HHV-6), and AdV in allogeneic HCT recipients (ALVR105, IND 015092). To 
determine whether a similar strategy could be applied to treat community-acquired respiratory 
viruses (CARVs), AlloVir conducted the following studies: 1) explored the cellular immune 
response directed against RSV, IFV, PIV, and hMPV; 2) assessed the feasibility of expanding T 
cells reactive against immunodominant antigens within each of the target viruses; 3) performed in 
vitro characterization studies to assess the effector and safety profile of such cells; and 4) sought 
evidence that T cell immunity played a protective role by examining the endogenous immune 
response in allogeneic HCT recipients with active infections. 
See the Investigator’s Brochure for further information regarding the nonclinical studies conducted 
with ALVR106. 
1.5 
Overview of Clinical Experience with Similar VST Platforms to ALVR106 
No clinical data with ALVR106 is currently available. This study is the first study evaluating 
ALVR106 in humans.  
The use of virus-specific T cells developed using the same platform as ALVR106 has been in the 
clinic for the treatment of viral infections in immunocompromised patients including HCT and 
SOT recipients. The below preliminary clinical data offers some guidance on what we would 
anticipate the safety of ALVR106 to be in HCT and SOT patient populations for the treatment of 
respiratory viral infection associated with 1 or more of the target viruses.  
1.5.1 
ALVR109: VST in the Treatment of COVID-19 Lower Respiratory Tract Infection    
ALVR109, is an allogeneic, VST targeting SARS-CoV-2 virus. ALVR109 
 
 
 cells 
 has been administered to 12 immunocompromised patients with 
lower respiratory tract infection (LRTI) associated with COVID-19 infection.32 Of the 12 patients, 
4 patients were enrolled in a Phase 1 study (IND # 23426) and 8 patients were administered 
ALVR109 as compassionate use under emergency INDs.  Preliminary data was available in 9 
LRTI participants (4 Phase 1 patients and 5 compassionate use patients) that had received at least 
1 infusion with at least 28 days of follow up post-initial infusion. Of the 9 patients the mean age 
was 60 y old and 5 were male. The risk factors included: 6 post-transplant patients (1 heart 
transplant, 2 lung transplants, and 3 bone marrow transplants), 2 patients were >65y old with 
comorbidities, and 1 patient was pre-transplant with diffuse large B cell lymphoma (DLBCL). A 

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majority of patients (n=8) had received and failed treatment with remdesivir and corticosteroids, 
and 6 were receiving supplemental oxygen, with one of these patients being on a ventilator at the 
time of first ALVR109 infusion. Of the 9 LRTI patients, all showed clinical improvement post-
ALVR109 infusion with 8 of 9 achieving suppression of SARS-CoV-2. No patients experienced a 
treatment-related adverse event. One post-BMT patient experienced cytokine release syndrome 
(CRS) on Day 13 post infusion but was considered by the investigator to be related to COVID-19 
disease progression and not ALVR109. Three LRTI patients died during follow up for reasons 
related to underlying disease: 1 post-BMT patient showed initial signs of viral decline and clinical 
improvement before worsening with progression of COVID-19 on Day 26, and ultimately died; 1 
patient with DLBCL died due to the cancer, and 1 lung transplant patient died of organ failure. 
Autopsy of the lung transplant patient showed no evidence of SARS-CoV-2 infection by lung in-
situ hybridization (ISH).  Overall, the preliminary safety profile has demonstrated VST are 
generally safe and well tolerated in immunocompromised patients with lower respiratory tract 
infection and support further evaluation of VSTs for treatment of respiratory tract infection. 
1.5.2 
Posoleucel (ALVR105): VST in the Treatment of Viral Infection in HCT Patients 
To investigate the safety and clinical efficacy of posoleucel, a multivirus-specific T cell product 
reactive for BKV, AdV, HHV-6, EBV, and CMV generated from third-party, healthy, eligible 
donors, a Phase 2 clinical study was conducted in recipients of allogeneic HCT with drug- 
refractory infections with ≥1 of the 6 viruses targeted by posoleucel (patients infected with JCV 
were also eligible) (Tzannou, 2017). In this open-label study, patients received a single IV infusion 
of 
 
 HLA-matched posoleucel cells
, with the option to receive a second infusion 
 and additional infusions 
 
thereafter. Therapy with standard antiviral medications could be continued at the discretion of the 
treating physician. 
Of the 82 patients screened for participation in this study, two (2.4%) could not be enrolled due to 
inability to provide an appropriately HLA-matched posoleucel drug product. A total of 58 patients 
with persistent and/or refractory virus infections following allogeneic HCT were infused with 
posoleucel drug products matched at 1 to 6 HLA antigens (the first 38 patients to complete the 
study are reported in Tzannou et al, 2017). Thirty (n=30) participants were male and 28 (n=28) 
were female. Participant ages ranged from 2 to 73 years with a mean age of 32.7 years.  
Thirty-nine participants (67.2%) each received 1 infusion of posoleucel, 15 (25.9%) received 
2 infusions (including one participant who was enrolled twice, each for a different viral infection), 
and 4 (6.8%) received 3 infusions. All infusions were administered in full. Of the 58 participants 
who received at least 1 infusion of posoleucel, 46 participants had a single target virus identified 
at study entry for their initial infusion of posoleucel (including the one participant who was 
enrolled twice in the study, each time for a single target virus), 11 participants had two, and 
one participant had three target viruses identified concomitantly at the time of initial infusion of 
posoleucel. Of the 70 target virus infections confirmed at study entry, 27 (38.6%) infections were 
BKV, 12 (17.1%) were AdV, 4 (5.7%) were HHV6, 2 (2.9%) were EBV, 1 (1.4%) was JCV, and 
24 (34.3%) infections were CMV.  

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Infusion with posoleucel was generally well tolerated, with an adverse event profile reflective of 
the underlying clinical status of a patient population that had undergone allogeneic HCT that was 
subsequently complicated by infection/reactivation by one or more of the viruses targeted by 
posoleucel (AdV, BKV, CMV, EBV, and HHV6), and/or JCV. None of the patients developed 
cytokine release syndrome (CRS). Thirteen of 58 (22%) participants were documented with acute 
GVHD within 42 days of their last VST infusion; the majority of these were mild and resolved, 
and 1 of these (1.7% of all 58 participants) developed acute GVHD Grade III, the only participant 
with an acute GVHD severity exceeding Grade II, a primary safety endpoint. Seven of the 36 
(19%) participants with chronic GVHD assessments recorded were diagnosed with chronic GVHD 
at 3, 6, and/or 12 months after infusion of posoleucel. These rates are consistent with the expected 
published incidence of acute and chronic GVHD in this patient population.33 
The antiviral efficacy of posoleucel was demonstrated by the high proportion of participants with 
persistent and/or refractory viral infections that achieved a clinical antiviral response to 
posoleucel infusion. Of the 46 participants with a single target virus at study entry, 45 (97.8%) 
were reported to have either a partial response, PR (37/45, 82.2%) or complete response, CR 
(8/45, 17.8%) at the 6-week assessment after their initial infusion of posoleucel. Of the 
12 participants with more than 1 target virus identified concomitantly at study entry, 10 (83.3%) 
were reported to have either a PR or CR for all evaluable target viruses at the 6-week assessment 
after their initial infusion of posoleucel. Taken together, 55 of all 58 participants (94.8%) 
experienced a PR or CR by the 6-week assessment after their initial infusion of posoleucel. 
Overall, this study supports the feasible, safe, and effective use of posoleucel, a partially HLA-
matched, allogeneic, banked VST cell product for the treatment of clinically important viral 
infections in the hematopoietic cell transplant recipient population. 
1.5.3 
Posoleucel: VSTs in the Treatment of Viral Infection in SOT Patients 
This ongoing Phase 2 randomized, placebo-controlled, proof-of-concept study evaluating the 
safety, tolerability and effectiveness of posoleucel (ALVR105) to treat BK viremia in kidney 
transplant recipients. The study consists of 3 blinded treatment arms: 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blinded preliminary safety data review from this ongoing study was available in 37 participants 
that have been randomized and received at least 1 infusion with a median follow up of 41 days. 
There have been 12 adverse events considered treatment related by the investigator: headache 

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(n=6), chills (n=3), nausea (n=2), and dizziness (n=1); all were Grade 1 (mild) in severity. There 
have been no SAEs, deaths, or early treatment discontinuations reported. No AE of special 
interest (e.g. cytokine release syndrome (CRS), infusion related reactions (IRR) or acute/chronic 
GvHD) have been reported and no adverse effect on the transplanted organ or evidence of VST 
versus host disease has been observed to date. The safety profile to date is consistent with other 
published studies that have demonstrated VST are safe and well tolerated in SOT patients.   
Overall, the preliminary safety data in this Phase 2 study which demonstrates the lack of VST 
versus host disease, acute GVHD, and CRS, to date, supports the safe use of VSTs to target viral 
infection in a transplanted organ and in SOT patients in general.  
1.6 
Rationale 
Community acquired respiratory viruses are a significant cause of morbidity and mortality among 
immunocompromised transplant (e.g. HCT and SOT) recipients. Effective therapies are available 
only for IFV, and also to some extent for RSV infection, but no options exist for hMPV or PIV. 
Even with the current IFV options, immunocompromised patients are at increased risk of 
developing drug resistant IFV infections due to the increase in viral replication and shedding that 
occurs in the absence of an immune response. Preventive measures are also lacking, as vaccination 
is only available against IFV at this time. Given the severe implications respiratory viral infections 
have on the immunocompromised population, development of new treatment options is needed.  
In healthy individuals, T cell immunity defends against RSV, IFV, PIV, and hMPV. In HCT and 
SOT recipients, the delay in immune reconstitution post HCT and the use of potent 
immunosuppressive regimens to prevent GvHD or organ rejection leaves patients susceptible to 
severe viral infections. Co-infections in the context of immunocompromised HCT or SOT 
recipients can occur and there exists a significant unmet need for new cellular therapy to address 
these infections.34   
AlloVir’s approach is to restore T cell immunity by the administration of ex vivo expanded, 
non-genetically modified VSTs that may control viral infections and alleviate/eliminate symptoms 
until the transplant patient’s innate immunity is restored.  To achieve this goal, AlloVir will use 
VSTs manufactured from PBMCs procured from healthy, pre-screened (for infectious agents and 
disease risk factors as mandated by FDA 21 CFR part 1271, subpart C) donors that have had prior 
exposure to the 4 target viruses (RSV, IFV, PIV, and hMPV). These VSTs will be available as a 
partially HLA-matched “off the shelf” product.  
The aim of this two-part study is to evaluate the safety and tolerability of ascending doses of 
ALVR106 in combination with the current standard of care for the treatment of RTI in 
immunocompromised patients (Part A) and the antiviral activity of a selected ALVR106 dose in 
an expansion cohort (Part B). This study will enroll both HCT and SOT immunocompromised 
patient populations. Treatment response to ALVR106 in HCT and SOT immunocompromised 
patients with RTI is not anticipated to be impacted by the type of transplant a patient had undergone 
prior to enrollment. Preclinical data has demonstrated that ALVR106 consists of CD4+ and CD8+ 
memory T cells targeting the 4 respiratory viruses. Stimulation of ALVR106 in the presence of 
antigen would lead to a virus specific immune response and not a generalized immune response, 
lowering the risk of off-target effects in transplant patients, including risks of organ rejection, graft 
versus host disease, and cytokine release syndrome. Current data in VSTs (Section 1.5, posoleucel 

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and ALVR109) would support the use of ALVR106 VSTs in immunocompromised patients after 
HCT or SOT for treatment of RTI.  
1.7 
Risk/Benefit 
1.7.1 
Potential Risks 
ALVR106 specifically targets cells infected with RSV, IFV, PIV, and/or hMPV. The main 
potential risks of administration are enhanced inflammation at sites of viral infection and graft 
versus host disease (GVHD) due to cross reactivity with alloantigens in HCT recipients. 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 clinical study, in which ALVR105 (a multivirus-specific T cell product reactive for 
BKV, AdV, HHV-6, EBV, and CMV) was administered to allogeneic HCT recipients with drug-
refractory infections with 1 of the 5 target viruses.35   
The risk that adoptively transferred partially HLA-matched ALVR106 will cause Grade 2 or higher 
acute GVHD has been demonstrated to be low, according to data from previous studies with third 
party multivirus-specific T cells. If any patient develops GVHD, that patient will receive standard 
GVHD treatment at the discretion of the Investigator. The risk that adoptively transferred VST can 
cause VST versus host disease in SOT patients is low as the VST will target only target virus 
infected cells. As stated above, there have been no cases of GVHD in 37 kidney transplant patients 
with BK viremia administered up to 8 doses of posoleucel (ALVR105).    
Studies of donor-derived VSTs suggest that VSTs do not persist in patients who receive 
methylprednisolone in doses of 1 mg/kg. Therefore, if patients develop severe inflammatory 
reactions thought to be attributable to ALVR106, a therapeutic option is to administer 
methylprednisolone (1 to 2 mg/kg). In patients who develop skin rash or skin GVHD, excellent 
responses have been seen with administration of topical steroids.   
Cytokine release syndrome (CRS) is the most common serious complication arising from infusion 
of chimeric antigen receptor (CAR) T cells; however, the infused T cells in this study do not 
express a CAR and are not genetically modified. Thus, the risk of CRS is low. However, case 
reports of CRS with VSTs have been reported in the setting of bulky EBV disease.23 Therefore, 
CRS remains a theoretical possibility, at least in patients who are infected with EBV and have 
expansive disease. To ensure that any potential cases of CRS are discovered in a timely manner, 
CRS has been included as an AE of special interest. Patients will be closely monitored for signs 
or symptoms of CRS, which include constitutional symptoms (fever, rigors, headache, malaise, 
fatigue, nausea, vomiting, and arthralgia), vascular (hypotension), cardiac (arrhythmia), 
respiratory compromise, renal (kidney failure and uremia), and laboratory (including coagulopathy 
and a hemophagocytic lymphohistiocytosis-like syndrome). The development of CRS of any grade 
will necessitate urgent medical assessment and immediate notification of the Medical Monitor. 
Multiple reports have established that IL-6 is a key cytokine involved in severe cytokine release 
syndrome (sCRS). Infusion of tocilizumab (an IL-6R monoclonal antibody) has rapidly eradicated 
symptoms of sCRS. The established dose of tocilizumab for treatment of CRS is 8 mg/kg 
intravenously (IV) infused over 1 hour for children and adults (maximum single dose of 800 mg). 
A lower dose can be administered at the discretion of the physicians caring for the patient. Doses 
can be repeated if symptoms are not improved within 12 to 24 hours. 

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Possible side effects of infusion include allergic reaction (anaphylaxis), decreased oxygenation, 
nausea/vomiting, arrhythmia, and hypertension. 
1.7.2 
Potential Benefits 
A serious unmet medical need exists for immunocompromised patients experiencing viral 
infections following HCT or SOT. Community acquired respiratory viral infections involving IFV, 
RSV, PIV, and hMPV have been attributed to mortality caused by progression to lower respiratory 
tract infection (LRTI) such as pneumonia and bronchiolitis in immunocompromised HCT and SOT 
patients, and specific to lung transplant recipients, bronchiolitis obliterans syndrome (BOS) or 
chronic lung allograft dysfunction (CLAD).4,36,37 With changes in transplant practices, their 
severity is increasing and the timeframe when patients are subjected to potentially fatal infections 
has expanded. Mortality from these infections can be as high as 23% to 50% for HCT patients with 
pneumonitis. In SOT, especially lung transplant recipients, mortality rates due to progression to 
LRTI are as high as 20%.38 ALVR106 has the potential to address such a serious unmet medical 
need.   
The nonclinical data have shown that it is feasible to generate a single preparation of polyclonal 
multi-respiratory VSTs with specificities directed to IFV, RSV, PIV, and hMPV in clinically 
relevant numbers using Good Manufacturing Practice compliant methodologies. These results 
support the clinical importance of T cell immunity in mediating protective antiviral effects against 
CARVs and demonstrate the feasibility of utilizing a broad-spectrum immunotherapeutic in 
immunocompromised patients 
with 
uncontrolled 
infections. Such a 
broad-spectrum 
immunotherapeutic may provide an important treatment benefit to immunocompromised 
individuals suffering from respiratory infections.  

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2 
STUDY OBJECTIVES 
2.1 
Part A (Dose Escalation) 
2.1.1 
Primary Objective 
The primary objective of Part A is to determine the safety and tolerability of ascending doses of 
ALVR106 when administered to high-risk adult patients with upper respiratory tract infections 
(URTIs) caused by RSV, IFV, hMPV, and/or PIV following HCT or SOT. 
2.1.2 
Secondary Objectives 
The secondary objectives of Part A are the following: 
• To identify the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) 
of ALVR106 in patients with URTIs 
• To characterize the individual patient antiviral response as measured by change in viral load 
from nasal swab specimens from baseline through Day 28 following the patient’s first 
ALVR106 infusion  
2.1.3 
Exploratory Objectives 
The exploratory objectives of Part A are the following: 
• To characterize the individual patient antiviral response as measured by change in viral load 
from nasal swab specimens from baseline through Day 60 following the patient’s first 
ALVR106 infusion 
• To describe the individual patient antiviral response as measured by the percent change in 
viremia from baseline through Day 28 and Day 60 following the patient’s first ALVR106 
infusion 
• To assess the effect of ALVR106 on time to resolution of viremia. 
• To assess the effect of ALVR106 on target viral reinfection. 
• To determine improvement and resolution of clinical symptoms of URTI following the 
patient’s first ALVR106 infusion 
• To determine the proportion of patients with progression from URTI to LRTI or worsening 
LRTI as defined by new onset LRTI symptoms (eg, shortness of breath, fever, fatigue, 
coughing, chest discomfort, production of mucus, coarse crackles) and either a sustained 
oxygen saturation <90% while breathing ambient air at rest, or new findings on chest X-rays 
and/or CT scans suggestive of progressive lung involvement.  
• To describe overall and LRTI-related mortality in adult patients treated with ALVR106 
• To determine the duration of oxygen dependency, defined as the inability to maintain an 
oxygen saturation 90% in the absence of supplemental oxygen, in adult patients treated with 
ALVR106 
• To determine viral genotypic changes from baseline associated with single and/or multiple 
infusions of ALVR106, when applicable 

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• To assess the effect of ALVR106 for resolution, improvement, stability, or progression of 
LRTI as measured by imaging 
2.2 
Part B (Recommended Phase 2 Dose Cohort Expansion) 
2.2.1 
Primary Objective 
The primary objective of Part B is to determine the antiviral activity of the RP2D of ALVR106, 
as compared to placebo, when administered to high-risk adult patients with URTIs caused by RSV, 
IFV, hMPV, and/or PIV following HCT or SOT. 
2.2.2 
Secondary Objectives 
The secondary objectives of Part B are the following: 
• To determine the safety and tolerability of the RP2D of ALVR106 when administered to high-
risk adult patients with URTIs caused by RSV, IFV, hMPV, and/or PIV following HCT or 
SOT  
• To characterize the individual patient antiviral response as measured by the percent reduction 
in viral load from nasal swab specimens and a reduction in clinical signs and symptoms from 
baseline through Day 28, Day 60, Day 90, and Month 6 following the patient’s first ALVR106 
infusion  
2.2.3 
Exploratory Objectives 
The exploratory objectives of Part B are the following: 
• To characterize the individual patient antiviral response as measured by the percent change in 
viremia from baseline through Day 28, Day 60, and Month 6 following the patient’s first 
ALVR106 infusion 
• To assess the effect of ALVR106 on time to resolution of viremia. 
• To assess the effect of ALVR106 on target viral reinfection. 
• To determine viral genotypic changes from baseline associated with single and/or multiple 
infusions of ALVR106, when applicable 
• To determine improvement and resolution of clinical symptoms of URTI following the 
patient’s first ALVR106 infusion 
• To determine the proportion of patients with progression from URTI to LRTI or worsening 
LRTI as defined by new onset LRTI symptoms (eg, shortness of breath, fever, fatigue, 
coughing, chest discomfort, production of mucus, coarse crackles) and either a sustained 
oxygen saturation <90% while breathing ambient air at rest, or new findings on chest X-rays 
and/or CT scans suggestive of progressive lung involvement.  
• To describe overall and LRTI-related mortality in adult patients treated with ALVR106 
• To assess long-term safety of ALVR106 through Day 365 

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• To determine the duration of oxygen dependency, defined as the inability to maintain an 
oxygen saturation 90% in the absence of supplemental oxygen, in adult patients treated with 
ALVR106 
• To assess the effect of ALVR106 for resolution, improvement, stability, or progression to 
LRTI as measured by imaging 

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3 
STUDY DESCRIPTION 
3.1 
Summary of Study Design 
This is a Phase 1/2, double-blind, placebo-controlled, dose escalation and expansion study to 
assess the safety and dose selection of ALVR106 in addition to standard of care for the treatment 
of high-risk patients with RTIs and clinical manifestations caused by RSV, IFV, hMPV, and/or 
PIV following transplant. This study will be conducted in 2 parts:  
• Part A (Dose Escalation)   
• Part B (RP2D Cohort Expansion)   
Throughout the study, all patients may receive standard of care as determined by the Investigator 
(or designee). Reference Protocol Section 5.7 for additional information on concomitant 
medications. 
The specific ALVR106 drug product for infusion selected for each participant will be determined 
by an electronic software system (CytoMatch™) based on the 
 
 
Reference the JUDI Manual for additional details.  
During the study, the severity of adverse events will be graded by the Investigator according to 
the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) v5.0. All hospitalizations, intensive care unit (ICU) admissions and SAEs will be 
reported and will be assessed as to whether caused by the RTI.   
Changes in patient reported respiratory status will be captured in the patient reported respiratory 
clinical symptoms form (reference Appendix D) and not as adverse events. A new diagnosis of 
lower respiratory tract infection (LRTI) will be captured as an AE. Any respiratory events which 
meet SAE criteria will be captured as both an AE and SAEs. Respiratory status with imaging 
will be assessed by the investigator and graded using the Radiation Therapy Oncology Group 
Lung Toxicity Scale presented in Table 2.  
Table 1. Radiation Therapy Oncology Group Lung Toxicity Scale 
Organ 
Tissue 
0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Lung 
None 
Asymptomatic or 
mild symptoms 
(dry cough) 
Slight 
radiographic 
appearances 
Moderate 
symptomatic 
fibrosis or 
pneumonitis 
(severe cough) 
Low grade 
fever 
Patchy 
radiographic 
appearances 
Severe 
symptomatic 
fibrosis or 
pneumonitis 
Dense 
radiographic 
changes 
Severe 
respiratory 
insufficiency/ 
Continuous 
oxygen/ 
Assisted 
ventilation 
 

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An independent Safety Review Committee (SRC) will be convened for this study to routinely 
monitor safety in a blinded fashion, unless the SRC makes a specific request for individual patient 
unblinding. Further details can be found in the SRC Charter. 
Figure 1 provides a summary of the study design. 
Figure 1. Summary of Study Design 
 
3.1.1 
Part A (Dose Escalation)   
Part A will include up to 4 cohorts, with 4 high-risk adult patients per cohort (potentially expanding 
to 8 patients per cohort), randomized in a 
 ratio to ALVR106 or placebo in a double-blind 
fashion. Patients in each cohort will receive an infusion of ALVR106 cells or placebo on Day 1 
and will return to the clinical site for assessment on Days 3, 7, 10, and 14 or more frequently as 
determined by the patient’s clinical condition at the discretion of the Investigator and in 
collaboration with the Medical Monitor.  
Administration of the 
 dose will be based on 
 visit assessments (reference 
Sections 5.1 and 5.6.3 for additional information on dose administration). 
Follow-up visits will occur at Day 28 (Week 4), Day 60 (Week 8), Day 180 (Month 6), and 
Day 365 (Month 12) following the patient’s first study treatment infusion. All patients will follow 
the same schedule of follow-up visits, including any patients who receive a partial infusion (less 
than the recommended dose for the patient). 
The planned doses for Cohorts 1 through 4 are presented in Table 2. Intra-patient dose escalation 
is not permitted. 

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Table 2. Planned Doses for Cohorts 1 Through 4 
Dose Cohort 
ALVR106 Dose Level 
1 
 
 
  
2 
 
 
 
3 
 
 
 
4 
 
 
 
In the event of toxicity at a planned dose, the doses may be de-escalated, based on 
recommendations from the SRC, to an interpolated intermediate dose from the planned cohorts as 
presented below. 
Intermediate Doses  
Dose Cohort 
ALVR106 Dose Level 
Toxicity adjusted dose 
between Dose Cohort 1 
and 2 
 
 
  
Toxicity adjusted dose 
between Dose Cohort 2 
and 3 
 
 
 
 
For each dosing cohort in Part A, the SRC will review the safety and available efficacy data after 
the first two patients have completed at least 7 days of safety monitoring following the initial 
dose. No additional patients will be dosed until that review is completed. Once review of the first 
two patients is complete (and the SRC has endorsed continuation of the study) the study 
enrollment of the remaining patients in the cohort will continue. 
At least one week after the last patient’s first dose in each cohort, the SRC will convene to assess 
blinded safety data from the current cohort and, if applicable, previous cohorts. This will allow 
for a consolidated safety review, with patients within the cohort averaging at least 14 days post 
the last dose. 
Dose escalation will proceed to identify the maximum tolerated dose (MTD) within the planned 
dose range and a recommended Phase 2 dose (RP2D) that may be the MTD or a lower dose 
within the tested dose range.  
Based on routine safety reviews, the SRC may recommend escalating the dose as planned, 
recommend an intermediate dose, recommend expansion of the current cohort, recommend 
stopping dose escalation (Part A), or stop the study. In the event of cohort expansion, up to 4 
additional patients may be enrolled and randomized in a 
 ratio to ALVR106 or placebo. In 
addition, the SRC will make a recommendation for the RP2D and starting enrollment of Part B.  
The Sponsor will determine the final RP2D based on SRC recommendation and after review of 
all available relevant safety data through at least Day 28 following the first ALVR106 or placebo 
infusion. Reference the SRC Charter for additional information.  

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3.1.2 
Part B (Recommended Phase 2 Dose Cohort Expansion)   
Following the determination of the RP2D in Part A, based on review of safety and efficacy data, 
approximately 45 high-risk adult patients with URTIs will be randomized in a 
 ratio to 
ALVR106 or placebo in a double-blind fashion.  
Patients in the ALVR106 group will receive an infusion of the RP2D as determined in Part A. 
Patients will receive an infusion of ALVR106 cells or placebo on Day 1 and will return to the 
clinical site for assessment on Days 3, 7, 10, and 14.  
Administration of the 
 visit assessments (reference 
Section 5.6.3 for additional information on dose administration). 
Additional follow-up visits will occur at Day 28 (Week 4), Day 60 (Week 8), Day 90 (Month 3) 
Part B only, Day 180 (Month 6), and Day 365 (Month 12). All patients will follow the same 
schedule of follow-up visits, including any patients who receive a partial infusion (less than the 
recommended dose for the patient). 
The SRC will continue to routinely monitor safety in the expansion cohort. Further details can be 
found in the SRC Charter.  
3.2 
Dose-Limiting Toxicity 
DLTs are defined as treatment-related Grade ≥3 SAEs and/or Grade >3 adverse event of special 
interest (AESI) that emerge or worsen during the study. Treatment-related AEs are those that 
cannot be reasonably attributed to the patient’s underlying disease, other medical condition, or 
concomitant medications.  
The AESI for this study are included in Section 7.2.4. 
3.3 
Stopping Rules 
Stopping rules for Parts A and B are defined as 
A patient with a DLT which is a Grade ≥3 SAE or a Grade ≥3 AESI that emerges or worsens 
during the study period following the patient’s initial dose and cannot be reasonably attributed to 
the patient’s underlying disease, other medical condition, or concomitant medications.  The study 
enrollment would pause to allow time for a safety review by the SRC. 
Focusing on AESI will provide further assurance that emergent safety issues are identified 
promptly. The AESI for this study were selected based on the need to identify potential worsening 
in the underlying disease being targeted, as well as theoretical complications of VSTs.  
The AESI for this study are included in Section 7.2.4. 
The SRC will consist of an independent Chairperson and two additional independent experts in 
the field, at least one of the members will be a transplant physician and at least one member will 
be an infectious disease expert. In addition, an unblinded statistician (responsible for generating 
and submitting unblinded data of individual adverse events to the SRC upon request) will also be 
members of the SRC.  
 
The SRC will meet at least every 2 weeks to review emerging safety data and will conduct both 
open and closed meetings. Should any safety issues require review by the SRC, an emergency 

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meeting will be scheduled within 72 hours. Should a death occur in the study that is considered to 
be definitely or probably related to the study product by the Investigator, the SRC will meet on an 
urgent basis, within 72 hours, to review the data available and make an assessment. Further dosing 
will be stopped until the SRC makes an assessment.  
 
The SRC will also convene following any Grade 4 or 5 SAE, irrespective of relatedness, or a Grade 
≥3 SAE that may possibly, probably, or definitely be related to study treatment. 
 

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4 
SELECTION AND WITHDRAWAL OF PATIENTS  
4.1 
Inclusion Criteria 
Patients must meet all of the following criteria in order to be eligible to participate in the study: 
1. Willing and able to provide written informed consent to participate in the study. 
2. Aged 17 to 75 years at screening. 
3. Undergone hematopoietic cell (HCT) or solid organ (SOT) transplantation.   
a. HCT must have been performed ≥21 days prior to study treatment administration and 
demonstrated engraftment with an absolute neutrophil count >500/µL. 
b. SOT includes kidney, liver, heart, lung, pancreas, and/or intestines must have been 
performed ≥28 days prior to study treatment administration. Other SOT that requires 
immunosuppression to prevent organ rejection may be allowed with medical monitor 
approval. 
4. Detection of at least 1 target virus of interest (ie, RSV, IFV, hMPV, and/or PIV) in the 
respiratory tract obtained by nasal swab. For Screening, a local laboratory result obtained ≤3 
days before or during the screening period will be acceptable for eligibility determination in 
place of a central laboratory result. However, a baseline central nasal swab sample must be 
collected and submitted to the central laboratory prior to dosing on Day 1 for all eligible 
patients. 
5. Has at least 1 suitably matched ALVR106 drug product for infusion available. HLA Class I 
and II typing can be obtained during Screening.    
Note: If an ALVR106 drug product is not available, demographic data and HLA type will be 
collected. 
6. Diagnosis of respiratory tract infection, defined as new onset of at least 1 of the following 
respiratory symptoms prior to screening: nasal congestion, runny nose, cough, or sore throat, 
or worsening of 1 of these chronic respiratory symptoms (associated with a previously existing 
diagnosis, eg, chronic rhinorrhea, seasonal allergies, or chronic lung disease). Sign(s) or 
symptom(s) of respiratory tract infection must be present at the time of initial study drug 
administration on Day 1. 
7. Immunocompromised HCT or SOT patients considered by the investigator to be at high risk 
of viral respiratory disease progression. High risk may be determined based on the HCT 
transplant type (e.g. haploidentical donor, unrelated donor, undergone cord blood HCT, or ex 
vivo HCT graft manipulation), delay in immune reconstitution in HCT patients (e.g. 
lymphocyte count <180/mm3 or CD4 T cell count <50/mm3), time from transplant (e.g. <100 
days from transplant), and/or immunosuppressive regimens required post-transplant.    
8. A negative serum pregnancy test for female patients of childbearing potential. 
9. Female patients of childbearing potential and male patients with female partners must agree to 
use an effective contraceptive method during the study and for a minimum of 90 days after 
study treatment. 

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Note: A female is considered to be of “childbearing potential” if she has experienced menarche 
and is not permanently sterile or postmenopausal (postmenopausal is defined as 12 consecutive 
months with no menses without an alternative medical cause). 
Note: In addition to routine contraceptive methods, “effective contraception” also includes 
heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of 
pregnancy prevention), defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal 
ligation; however, if at any point a previously celibate patient chooses to become 
heterosexually active during the time period for use of contraceptive measures outlined in the 
protocol, he/she is responsible for beginning contraceptive measures. 
4.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from participation in the study: 
1. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose 
>0.5 mg/kg/day) within 7 days prior to screening. 
2. Prior therapy with abatacept or belatacept, within 3 months prior to screening; or 
antithymocyte globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-
targeted monoclonal antibodies within 28 days prior to study treatment administration. 
3. Infection with novel coronavirus disease 2019 (COVID-19) defined as positive antigen or 
detectable PCR result within 28 days prior to study treatment administration 
4. Significant hypoxemia (ie, oxygen saturation <90% while breathing ambient air at rest)   
5. Requirement for continuous infusions of inotropes or vasopressors for blood pressure support 
6. Systolic Blood Pressure <90 mmHg, except for patients with normal resting SBP <90 mmHg 
confirmed by investigator  
7. Requirement for mechanical ventilation or noninvasive ventilation  
8. Resting respiratory rate ≥30 breaths/min  
9. Evidence of encephalopathy or confusion 
10. For HCT or non-lung SOT, chest X-ray and/or CT scan with multifocal consolidation or diffuse 
alveolar consolidation. For lung transplant recipients, any new abnormalities on a chest X-ray 
and/or CT scan, other than patchy atelectasis, hyperinflation, and/or bronchial wall 
thickening39, caused by LRTI.  Images obtained within 3 days of screening will be acceptable 
to determine eligibility. All chest X-rays and/or CT scans will also be submitted for central 
reading, which will be used for analysis purposes.  
11. For HCT patients, evidence of Grade >2 acute GVHD; and for SOT patients, any history or 
evidence of GVHD (see Appendix B). 
12. For SOT patients, ABO incompatible or complement-dependent lymphocytotoxic crossmatch 
positive transplant (isolated positive B cell crossmatches are not an exclusion criterion) 
13. Presence of uncontrolled or progressive bacterial or fungal infections (ie, evidence of 
bacteremia, fungemia, disseminated, and/or organ-specific infection not well controlled by 
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14. Presence of progressive, uncontrolled viral infections not targeted by ALVR106 with evidence 
of end organ disease. 
15. Known or presumed non-viral pneumonia or sinusitis secondary to any organism. 
16. Known history or current (suspected) diagnosis of CRS associated with the administration of 
peptides, proteins, and/or antibodies. 
17. Receipt of any investigational agents, including antiviral treatment (not ALVR106 or placebo) 
targeting RSV, IFV, PIV, and/or hMPV, from 28 days or 5 half-lives (whichever is longer) 
prior to study treatment administration, unless approved by Medical Monitor.  
18. Donor lymphocyte infusion or other T cell therapies performed <21 days prior to study 
treatment administration. 
19. Aspartate aminotransferase or alanine aminotransferase serum levels >5 × the upper limit of 
normal (ULN) or direct bilirubin serum levels >2 × the ULN reference per central laboratory. 
20. Renal dysfunction, defined as estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 
m2 or require ongoing dialysis and/or renal replacement therapy at screening  
21. Relapse of primary malignancy other than minimal residual disease. 
22. Pregnant, breastfeeding, or planning to become pregnant during the study. 
23. Significant underlying lung disease that confounds the assessment of the URTI or LRTI 
episode or any condition that, in the opinion of the Investigator, would prevent full 
participation in this study or would interfere with the evaluation of any study endpoints. 
4.3 
Eligibility Confirmation 
Patients may receive up to 2 doses of study treatment. On Day 1, prior to dosing, the following 
eligibility criteria must be assessed. Patients who meet any of the following criteria on Day 1 will 
be excluded from participation in the study: 
1. No sign(s) or symptom(s) of respiratory tract infection present at the time of initial study drug 
administration. 
2. Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose 
>0.5 mg/kg/day). 
3. For HCT patients, evidence of Grade >2 acute GVHD; and for SOT patients, evidence of any 
GVHD (see Appendix B) 
4. Receipt of any investigational agents, including antiviral treatment (not ALVR106 or placebo) 
targeting RSV, IFV, PIV, and/or hMPV, not approved by Medical Monitor  
Prior to administration of the second dose, the following criteria must be assessed by the 
Investigator: 
1. Last available viral load result from nasal swab specimens analyzed at central lab 
2. Clinical status, specifically respiratory symptoms   
3. Last available imaging 
4. Evidence of GVHD and grade  

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If needed, Investigator should contact the Medical Monitor to discuss patient’s status. 
4.4 
Withdrawal Criteria 
Participation of a patient in this clinical study may be discontinued for any of the following 
reasons: 
• The patient withdraws consent 
• The patient requests discontinuation from study treatment for any reason 
• Occurrence of any medical condition or circumstance that exposes the patient to substantial 
risk and/or does not allow the patient to receive additional study treatment 
• Any SAE, clinically significant adverse event, severe laboratory abnormality, intercurrent 
illness, or other medical condition which indicates to the Investigator that continued receipt of 
study treatment is not in the best interest of the patient 
• Pregnancy 
• Requirement of prohibited concomitant medication 
• Patient failure to comply with protocol requirements or study-related procedures 
• Termination of the study by the Sponsor or the regulatory authority 
If a patient discontinues from the study early, before the Month 12 visit, due to the above criteria 
or any other reason, the patient should return to complete all assessments in the Month 12/early 
termination visit. If patient is not able to return to the site to complete the early termination visit, 
all efforts will be made to gather available information via a phone call. 
The reason for patient withdrawal must be documented in the electronic case report form (eCRF). 
In the case of patients lost to follow-up, attempts to contact the patient must be made and 
documented in the patient’s medical records. 
Withdrawn patients due to AE will not be replaced. 
4.5 
Screen Failures 
Screen failures are defined as participants 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 
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 SAE. 

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5 
STUDY TREATMENTS 
5.1 
Treatment Groups 
For Part A, patients who meet all of the inclusion criteria and none of the exclusion criteria will be 
enrolled and randomized in a 3:1 ratio to ALVR106 or placebo in a double-blind fashion. In a 
similar fashion, patients in Part B will be enrolled and randomized in a 2:1 ratio. The planned doses 
for Part A (dose escalation) are listed in Table 2. For Part B, ALVR106 will be administered at the 
RP2D as determined in Part A. The dosage in this study will be on a bracket-based per kg basis, 
as per Table 3. 
All patients will receive an infusion of ALVR106 cells or placebo on Day 1 and may receive 
additional infusions of blinded study treatment as detailed in Section 5.6.3. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In the event of toxicity at a planned dose, the doses may be de-escalated, based on 
recommendations from the SRC, to an interpolated intermediate dose from the planned cohorts as 
presented below. 
  
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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5.2 
Cohort Progression and Dose Escalation 
For each dosing cohort in Part A, the SRC will review the safety and available efficacy data after 
the first two patient have completed at least 7 days of safety monitoring following the initial dose. 
No additional patients will be dosed until that review is completed. Once review of the first two 
patients is complete (and the SRC has endorsed continuation of the study) the enrollment of the 
remaining patients in the cohort will continue. 
At least one week after the last patient’s first dose in each cohort, the SRC will convene to assess 
blinded safety data from the current cohort and, if applicable, previous cohorts. This will allow for 
a consolidated safety review, with patients within the cohort averaging at least 14 days post the 
last dose. 
The SRC may recommend escalating the dose as planned, recommend an intermediate dose, 
recommend expansion of the current cohort, recommend stopping dose escalation, or recommend 
stopping the study. In the event of cohort expansion, up to 4 additional patients may be enrolled 
and randomized in a 
 ratio to ALVR106 or placebo. Further details can be found in the SRC 
Charter. 
Dose escalation will proceed to identify the MTD within the planned dose range and, for Part A, 
an RP2D that may be the MTD or a lower dose within the tested dose range.  
5.3 
Rationale for Dosing 
The starting dose was chosen based on 1) previous human experience using adoptively-transferred 
donor-derived T cells18,19,20,23 and third-party–derived VSTs and 2) clinical precedent established 
using donor leukocyte infusions in the haploidentical stem cell transplant setting. 
Patients will receive no more than  doses in total. Patients that demonstrated improvement 
following the first dose but not resolution will receive the 
 
. 
 
 dose for patients that did not 
demonstrate improvement following the first dose. Data collected in real-time will be analyzed to 
monitor safety of ascending doses cumulatively. Should there be untoward effects of any of the 
doses, subsequent doses would not be administered to that patient. This is a first-in-man study, so 
the rationale for this dosing schema is derived from prior experience with other VSTs. 
5.4 
Randomization and Blinding 
For Part A, patients who meet all of the inclusion criteria and none of the exclusion criteria will be 
enrolled and randomized in a 
 ratio to ALVR106 or placebo in a double-blind fashion. In a 
similar fashion, patients in Part B will be enrolled and randomized in a 
 ratio. Randomization 
assignments will be performed by the Interactive Response Technology (IRT) system.  
The Sponsor designee (ie, IRT vendor) will have a designated randomization administrator who 
will maintain the randomization codes in accordance with standard operating procedures to ensure 
the blind integrity is properly maintained. Care should be exercised to ensure that only Sponsor 
personnel who require knowledge of treatment assignments will be unblinded (eg, staff involved 
in SAE reporting). Randomization information will be concealed from the Investigators and the 

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patients until the end of the study, with the exception of an emergency situation involving a patient 
who requires unblinding of the treatment assignment. 
5.5 
Breaking the Blind at Investigational Sites 
Unblinding should only occur in the event of an emergency or adverse event for which it is 
necessary to know the study treatment to determine an appropriate course of therapy. If possible, 
the Investigator should attempt to contact the site monitor or the Medical Monitor prior to 
unblinding in order to obtain additional information about the study treatment. If not possible, the 
Investigator should notify the site monitor or Medical Monitor as soon as possible of the 
unblinding without disclosing the treatment assignment of the unblinded patient. 
If the patient’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 patient’s source documentation in such a way as to avoid 
unblinding the treatment assignment to other site- or Sponsor-blinded personnel. The Investigator 
must document the patient’s identification, reason for breaking the blind, and the date and time of 
breaking the blind. 
5.6 
Drug Supplies 
5.6.1 
Formulation and Packaging 
ALVR106 is a third-party, donor-derived, “off-the-shelf” VST product with specificity for RSV, 
IFV, PIV, and hMPV. ALVR106 drug products will be checked for identity, phenotype, and 
sterility. The final product will be cryopreserved and ready for immediate use.  
ALVR106 drug product is cryopreserved under controlled rate conditions in cryovials and stored 
in the vapor phase of liquid nitrogen. Drug product vials will be 
 
 
. 
Cryopreservation media (without cells) will serve as the placebo and will be identical in volume 
and appearance to ALVR106. Cryopreservation media contains 
 
 
5.6.2 
Study Treatment Preparation and Dispensing 
ALVR106 (or placebo) will be supplied in a cryovial which is to be transported from vapor phase 
liquid nitrogen storage at the Current Good Manufacturing Practice BioStorage facility to the site 
of infusion location in a liquid nitrogen dewar or other suitable container. No additional 
preparation is required. 
5.6.3 
Study Treatment Administration 
The specific ALVR106 drug product for infusion selected for each participant will be determined 
by an electronic software system (CytoMatch™) based on the 
 
 
Reference the JUDI Manual for additional details.  
 

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For detailed instructions on ALVR106 or matching placebo administration reference the Cell 
Therapy Manual and Section 5.1 above for Part A, weight range-based dose to be administered.  
All eligible participants will be randomized to receive: 
ALVR106 cells or matching placebo administered IV over approximately minutes as a slow 
push on 
 if applicable. 
Administration of the 
 visit assessments, as follows: 
• Patients who have demonstrated an initial objective clinical response, and a decrease in 
viral load defined by at least 50% reduction of viral load in nasal swab, 
 
, if 
available.   
• Patients who have not demonstrated either clinical improvement or decrease in viral load 
in nasal swab following the first dose will receive 
 
.  If another partially HLA-matched 
drug product is not available, they will receive the same initial partially HLA-matched drug 
product or placebo.  
• Patients who have fully recovered will not receive
 Full recovery is defined 
as undetectable viral load in nasal swab by qPCR post first study treatment infusion, 
absence of respiratory symptoms, and, as applicable, normalization of imaging. 
• Patients who have experienced new onset of systemic GVHD (HCT and SOT patients), a 
Grade ≥3 worsening of GVHD (HCT patients) or Grade ≥3 infusion related reaction will 
not receive
  
Premedication can be administered to any participant at the investigators discretion but is not 
required, except for patients with a prior history of reaction to blood products (reference Section 
5.7.2 for premedication options).   
Post-infusion monitoring will be performed as indicated in Section 7.14. 
5.6.4 
Treatment Compliance 
ALVR106 (or placebo) will be administered IV and under the supervision of clinical study 
personnel at the site. 
5.6.5 
Storage and Accountability 
ALVR106 will be stored in the vapor phase of liquid nitrogen in a continuously monitored storage 
freezer. 
All material containing ALVR106 will be treated and disposed of as hazardous waste in 
accordance with governing regulations and clinical site procedures. 
ALVR106 accountability is the responsibility of the Principal Investigator and Sponsor. However, 
this responsibility may be delegated to a suitably qualified Investigator.   
Detailed records will be maintained to allow for accurate accountability of ALVR106. For further 
details and specifications, see the Study Investigational Medicinal Product Manual. 

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5.7 
Prior and Concomitant Medications and/or Procedures 
5.7.1 
Excluded Medications and/or Procedures 
The following medications and/or procedures are prohibited as specified below or from Screening, 
and through study Week 24: 
• Ongoing therapy with high-dose systemic corticosteroids (ie, prednisone equivalent dose 
>0.5 mg/kg/day) from 7 days prior to screening    
• Prior therapy with abatacept or belatacept, from 3 months prior to screening; or antithymocyte 
globulin, alemtuzumab (Campath-1H), or other immunosuppressive T cell-targeted 
monoclonal antibodies from 28 days prior to study treatment administration  
• Receipt of any investigational agents, including antiviral treatment (not ALVR106 or placebo) 
targeting RSV, IFV, PIV, and/or hMPV, from 28 days or 5 half-lives (whichever is longer) 
prior to study treatment administration, unless approved by Medical Monitor.  
• Donor lymphocyte infusion or other T cell therapies performed <21 days prior to study 
treatment administration      
• Mechanical ventilation  of any type within 1 month or noninvasive ventilation during screening 
prior to the administration of ALVR106 
• Ongoing dialysis and/or requirement for renal replacement therapy at screening 
5.7.2 
Permitted Medications and/or Procedures 
The following medications and/or procedures are permitted: 
• Throughout the study, all patients may receive standard of care as determined by the 
Investigator (or designee). This may include antivirals targeting RSV (eg, oral, IV, or inhaled 
ribavirin), IFV (eg, oseltamivir, zanamivir, peramivir, baloxavir), hMPV, and/or PIV, as well 
as other viruses; polyclonal IV immunoglobulin; antibiotics; or antifungals; in addition to 
standard of care treatment for the patient’s underlying disease (eg, immunosuppressants), 
which should be kept as stable as possible during the study. However, as noted in the exclusion 
criteria, the dose of systemic corticosteroids may not exceed a prednisone equivalent dose of 
0.5 mg/kg/day. 
• If respiratory exacerbation not related to bacterial or fungal infections and requiring systemic 
corticosteroids is observed, then high-dose systemic corticosteroids (ie, prednisone equivalent 
dose >0.5 mg/kg/day) may be initiated at the Investigator’s discretion. If acute GVHD Grade 3 
or 4 is observed, a standard protocol will be followed per the site (see Appendix B). If CRS is 
observed, a standard protocol will be followed per the site (see Appendix C). 
• Premedication can be administered to any participant at the investigators discretion but is not 
required, except for patients with a prior history of reaction to blood products who will receive 
premedication with 0.25 to 0.5 mg/kg (maximum dose of 25 mg) diphenhydramine (IV or 
oral), 5 to 10 mg/kg (maximum dose of 650 mg) acetaminophen (IV or oral), and/or Dipyrone 
0.5 to 1.0 g (IV) where approved (e.g. Brazil), prior to study treatment administration. 
Dipyrone, a nonsteroidal anti-inflammatory drug, should be used with caution in renally 
impaired patients. The use of corticosteroids as premedication is prohibited. 

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• Female patients of childbearing potential and male patients with female partners must agree to 
use an effective contraceptive method during the study and for a minimum of 90 days after 
study treatment. In addition to routine contraceptive methods, “effective contraception” also 
includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect 
of pregnancy prevention), defined as a hysterectomy, bilateral oophorectomy, or bilateral tubal 
ligation; however, if at any point a previously celibate patient chooses to become 
heterosexually active during the time period for use of contraceptive measures outlined in the 
protocol, he/she is responsible for beginning contraceptive measures. 
5.7.3 
Documentation of Prior and Concomitant Medication Use 
All medications used within 30 days of screening will be recorded. However, the following 
medications used within 30 days before screening do not need to be recorded: 
• Fluids 
• Electrolytes 
• Vitamins 
• Supplements  
• Mouth care 
• Laxatives 
• “As needed” medications   
At screening, all concomitant medications and concurrent therapies, including the ones listed 
above, will be documented as indicated in Appendix A. Dose, route, unit frequency of 
administration, indication for administration, and dates of medication will also be captured in 
source documents and on the appropriate eCRF. 

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6 
EFFICACY ASSESSMENTS 
6.1 
Efficacy Endpoints 
The primary efficacy endpoints include the following: 
• The reduction in viral load from nasal swab specimens from pre-dose through Day 28. Time-
weighted average change from baseline to Day 28 in log10 viral load will be measured by qPCR 
(based on the central laboratory) for Part A. 
• Proportion of patients with 50% reduction in viral load from nasal swab specimens and 
improvement in clinical signs and symptoms by least 1 grade for clinical signs and symptoms 
abnormal at baseline through Day 28 following the patient’s first ALVR106 infusion for Part 
B. 
The secondary efficacy endpoints include the following: 
• The reduction in viral load from nasal swab specimens (measured by qPCR) from baseline to 
Day 60, Day 90 (Part B only), and Month 6 (based on the central laboratory). 
The exploratory efficacy Endpoints include the following: 
• Percentage of patients needing oxygen supplementation or ventilation throughout the study.  
• Number of days with oxygen supplementation. 
• Length of hospital stay for RTI defined as time between the first dose of study treatment and 
discharge for patients initially hospitalized for RTI at inclusion. 
• Change from baseline in viral load area under the curve will be measured by qPCR (based on 
the central laboratory). 
• Time to resolution of viral load from nasal swab specimens for all target viruses (ie, RSV, IFV, 
hMPV, and/or PIV) over the 6-month study period. 
• Persistence of infused VSTs. 
• Incidence of target viral reinfections (ie, RSV, IFV, hMPV, and/or PIV). 
• Time to resolution of viremia for all target viruses (ie, RSV, IFV, hMPV, and/or PIV) over the 
6-month study period (only for patients with detectable viremia at baseline). Resolution of 
viremia will be defined by the lower limits of detection of the assays used. 
• Incidence of use of any other antiviral therapies targeting ALVR106 viruses during the study. 
• Proportion of patients with progression from URTI to LRTI or worsening LRTI as defined by 
new onset LRTI symptoms (eg, shortness of breath, fever, fatigue, coughing, chest 
discomfort, production of mucus, coarse crackles) and either a sustained oxygen saturation 
<90% while breathing ambient air at rest, or new findings on chest X-rays and/or CT scans 
suggestive of progressive lung involvement.  
• Proportion of patients with resolution, improvement, stability, or progression of LRTI as 
measured by imaging. 
• Overall survival, defined as time to death (from any cause) from the first dose of study 
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• LRTI-related mortality, defined as time to LRTI-related death from the first dose of study 
treatment. 
• Incidence of relapse or progression of the primary malignancy. 
6.2 
Viral Load Assessment 
Reference the laboratory manual for detailed instructions on nasal swab sample collection. 
Viral load from nasal swab specimens (measured by qPCR and analyzed in a central laboratory) 
will be assessed as indicated in the Schedule of Procedures. Central tests will be performed from 
baseline through the end of study. A nasal swab of both nostrils will be performed and sent to the 
central laboratory for analysis.  
Blood samples for assessment of viremia will be collected as indicated in the Schedule of 
Procedures and stored for possible analysis. 
An aliquot of the blood and nasal swab turbinate will be stored for possible viral genotypic or viral 
load analysis. 
6.3 
Imaging 
All patients will have screening imaging performed and analyzed locally as long as the imaging 
can be transmitted to the central reader. For Parts A and B, imaging will be repeated as needed in 
cases of suspected progression to LRTI. Patient management will be based on the local reading, 
but the final analysis of radiologic progression will be based on the central reader’s assessment. 
For Parts A and B imaging will be repeated at Days 10 and 28 for all patients, and as needed if 
clinically indicated. The central reader will compare subsequent imaging to the screening 
measurement to assess resolution, improvement, stability, or progression. Additional details will 
be provided in the study manual. Imaging performed to assess the RTI at non-protocol required 
visits will also be collected and sent to the central reader. 
Chest X-rays and/or CT scans will be performed as indicated in the Schedule of Procedures. 
6.4 
Reconstitution of Antiviral Immunity 
Patient plasma and PBMCs will be tested for virus-specific activity by functional studies including 
enzyme-linked immunospot assay with appropriate viral -specific peptide mixtures and available 
HLA -restricted epitope peptides, intracellular cytokine staining, cytokine profiling, and/or other 
assays as they become available for immune profiling purposes. 
Persistence of infused T cells will be tested using deep sequencing and additional tests to track the 
T cell receptor v-beta repertoire in the patient peripheral blood prior to and post-infusion. 
Sequencing will be limited to evaluation of the persistence of VSTs and not any other genetic 
evaluations. 
Patient plasma and PBMCs will be collected as indicated in the Schedule of Procedures. 
6.5 
Respiratory Clinical Signs/Symptoms 
The evolution of respiratory clinical signs/symptoms will be as assessed by the Investigator (or 
designee) and the patient (or caretaker) (see Appendix D) as indicated in the Schedule of 

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Procedures. Reference P-106-001 eCRF Completion Guidelines for additional information on both 
the investigator’s assessment and patient reported respiratory assessment.     
For lung transplant recipients, if required by the investigator to support assessment of respiratory 
status, a spirometry assessment may be completed by the patient at Baseline, Week 4, Months 6 
and 12. Spirometry should be collected in line with local standard clinical practice. 
Additionally, oxygen use and duration and outcome of hospitalization for LRTI will be captured. 

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7 
SAFETY ASSESSMENTS 
7.1 
Safety Endpoints 
Safety endpoints will include review of adverse events (AEs); adverse events of special interest 
(AESI), clinical laboratory abnormalities; changes in corticosteroid dosage; abnormalities in vital 
signs or physical examination findings (including heart and lung auscultation, skin, and 
ears/nose/throat). The AESI as reported by the Investigator include: 
• New (HCT and SOT patients) or worsening (HCT patients) of acute or chronic GVHD  
• Graft failure or rejection 
• Cytokine release syndrome (for the CRS grading scale, see Appendix C) 
• Infusion related reactions (IRRs) 
• New or worsening interstitial pneumonitis as reported by the Investigator from review of 
radiologic findings  
• Progressive dyspnea   
On treatment data will be analyzed separately and include treatment-emergent safety data from the 
first dose of study drug to the last dose of study drug plus 12 weeks.  
7.2 
Adverse Events 
An adverse event is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment. An adverse event can therefore be any unfavorable and/or unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of an investigational medicinal product, whether or not related to the investigational medicinal 
product. All adverse events, including observed or volunteered problems, complaints, or 
symptoms, are to be recorded on the appropriate eCRF. 
Adverse events, which include clinical laboratory test variables, will be monitored and 
documented from the time of informed consent. Patients should be instructed to report any adverse 
event that they experience to the Investigator, whether or not they think the event is due to study 
treatment. 
Wherever possible, a specific medical diagnosis rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if a 
medical diagnosis is not initially known the Investigator should record the sign or symptom as  
separate adverse event on the eCRF. Additionally, the underlying condition that led to a medical 
or surgical procedure (eg, surgery, endoscopy, tooth extraction, or transfusion) should be recorded 
as an adverse event, not the procedure itself.  
Any medical condition already present at screening should be recorded as medical history and not 
be reported as an adverse event unless the medical condition or signs or symptoms present at 
baseline changes in severity, frequency, or seriousness at any time during the study or is a result 
of a study procedure. In this case, it should be reported as an adverse event. 
All respiratory symptoms will be captured on a Respiratory Status CRF and not as adverse events. 
A new diagnosis of lower respiratory tract infection (LRTI) will be captured as an AE. Any 

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respiratory events which meet SAE criteria will be captured as both an AE and SAEs. All 
hospitalizations, ICU admissions and SAEs will be reported and will be assessed as to whether 
caused by the RTI.  
Clinically significant abnormal laboratory or other examination (eg, electrocardiogram [ECG]) 
findings that are detected during the study or are present at screening and significantly worsen 
during the study should be reported as adverse events, as described below. The Investigator will 
exercise his or her medical and scientific judgment in deciding whether an abnormal laboratory 
finding or other abnormal assessment is clinically significant. Clinically significant abnormal 
laboratory values occurring during the clinical study will be followed until repeat tests return to 
normal, stabilize, or are no longer clinically significant. Abnormal test results that are determined 
to be an error should not be reported as an adverse event. Laboratory abnormalities or other 
abnormal clinical findings (eg, ECG abnormalities) should be reported as an adverse event if any 
of the following are applicable: 
• If an intervention is required as a result of the abnormality 
• If action taken with the study treatment is required as a result of the abnormality 
• Based on the clinical judgment of the Investigator 
7.2.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product means that a causal 
relationship between a medicinal product and an adverse event is at least a reasonable possibility, 
ie, the relationship cannot be ruled out. 
7.2.2 
Unexpected Adverse Drug Reaction 
An Unexpected Adverse Drug Reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information. 
7.2.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each adverse event and will also categorize 
each adverse event as to its potential relationship to study treatment using the categories of related 
or not related. 
Assessment of Severity 
The severity of all adverse events, except for changes in respiratory status and imaging, which will 
be graded using the Radiation Therapy Oncology Group Lung Toxicity Scale (Table 1), should be 
graded according to the CTCAE version 5.0. For those adverse event terms not listed in the 
CTCAE, the following grading system should be used: 
• CTCAE Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
• CTCAE Grade 2: Moderate; minimal local or noninvasive intervention indicated; limiting age-
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• CTCAE Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living 
• CTCAE Grade 4: Life-threatening consequences; urgent intervention indicated 
• CTCAE Grade 5: Death related to the adverse event 
Causality Assessment 
The relationship of an adverse event to the administration of the study treatment is to be assessed 
according to the following definitions: 
No (unrelated, not related, unlikely to be related) – The time course between the administration of 
study treatment and the occurrence or worsening of the adverse event rules out a causal relationship 
and another cause (concomitant drugs, therapies, complications, etc) is suspected. 
Yes (possibly, probably, or definitely related) – The time course between the administration of 
study treatment and the occurrence or worsening of the adverse event is consistent with a causal 
relationship and no other cause (concomitant drugs, therapies, complications, etc) can be 
identified. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study treatment. This means that there are facts (evidence) or arguments to suggest a causal 
relationship. 
The following factors should also be considered: 
• The temporal sequence from study treatment administration- 
The event should occur after the study treatment is given. The length of time from study 
treatment exposure to the event should be evaluated in the clinical context of the event. 
• Underlying, concomitant, intercurrent diseases- 
Each report should be evaluated in the context of the natural history and course of the disease 
being treated and any other disease the patient may have. 
• Concomitant drug- 
The other drugs the patient is taking or the treatment the patient receives should be examined 
to determine whether any of them might be recognized to cause the event in question. 
• Known response pattern for this class of study treatment- 
Clinical and/or preclinical data may indicate whether a particular response is likely to be a 
class effect. 
• Exposure to physical and/or mental stresses- 
The exposure to stress might induce adverse changes in the recipient and provide a logical and 
better explanation for the event. 
• The pharmacology and pharmacokinetics of the study treatment (as applicable)- 
The known pharmacologic properties (absorption, distribution, metabolism, and excretion) of 
the study treatment should be considered. 

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7.2.4 
Adverse Events of Special Interest 
The Investigator will monitor each patient for clinical and laboratory evidence of pre-defined AESI 
throughout the patient’s participation in this study.  
The Investigator will assess and record any additional information on the AESI in detail on an 
adverse event form which must be submitted within 24 hours of awareness of the event. 
For this study, AESI include the following as reported by the Investigator: 
• New (HCT and SOT patients) or worsening (HCT patients) of acute or chronic GVHD  
• Graft failure and rejection 
• Cytokine release syndrome (for the CRS grading scale, see Appendix C). 
• Infusion related reactions (IRRs). Signs and symptoms of an IRR may include the following: 
headache, fever, facial flushing, pruritis, myalgia, nausea, chest tightness, dyspnea, vomiting, 
erythema, abdominal discomfort, 
diaphoresis, shivers, 
hypertension, 
hypotension, 
lightheadedness, palpitations, urticaria and somnolence 
• New or worsening interstitial pneumonitis as reported by the Investigator from review of signs 
and symptoms, and radiologic findings 
• Progressive dyspnea   
During the course of the study, additional AESI may be identified by the Sponsor. 
Adverse events of special interest must be recorded in the eCRF. 
7.3 
Serious Adverse Events 
An adverse event or adverse reaction is considered serious if, in the view of either the Investigator 
or Sponsor, it results in any of the following outcomes: 
• Death. 
• A life-threatening adverse event. 
Note: An adverse event or adverse reaction is considered “life-threatening” if, in view of either 
the Investigator or Sponsor, its occurrence places the patient at immediate risk of death. It does 
not include an event that, had it occurred in a more severe form, might have caused death. 
• Requires hospitalization or prolongation of existing hospitalizations, or prolonged admission 
to emergency room. 
Note: Any hospital admission with at least 1 overnight stay will be considered an inpatient 
hospitalization. An emergency room or urgent care visit without hospital admission will not 
be recorded as an SAE under this criterion, nor will hospitalization for a procedure scheduled 
or planned before signing of informed consent, or elective treatment of a pre-existing condition 
that did not worsen from baseline. However, unexpected complications and/or prolongation of 
hospitalization that occur during elective surgery should be recorded as adverse events and 
assessed for seriousness. Admission to the hospital for social or situational reasons (ie, no place 
to stay, live too far away to come for hospital visits, respite care) will not be considered 
inpatient hospitalizations.  

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• A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions. 
• A congenital anomaly/birth defect. 
• An important medical event. 
Note: Important medical events that do not meet any of the above criteria may be considered 
an SAE when, based upon appropriate medical judgment, they may jeopardize the patient and 
may require medical or surgical intervention to prevent 1 of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalizations, or the development of drug dependency. 
7.4 
Serious Adverse Event Reporting – Procedures for Investigators 
Initial Reports 
All SAEs occurring from the time of informed consent until study participation is complete must 
be reported to 
) within 24 hours of the 
knowledge of the occurrence. Once the study is completed, if the Investigator becomes aware of a 
new event occurring in a study participant that is thought to be causally related, or follow up to an 
event that was previously reported, the event should be reported to 
.  
To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed,
 Safety personnel will be notified 
electronically by the EDC system and will retrieve the form. If the event meets serious criteria and 
it is not possible to access the EDC system, send via email at 
 within 24 hours of awareness. 
 -7.7 
When the EDC system becomes available, the SAE information must be entered within 24 hours 
of the system becoming available. 
Follow-Up Reports 
The Investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the patient 
dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation 
(eg, patient discharge summary or autopsy reports) to Medpace Clinical Safety and/or 
 
via fax or email. If it is not possible to access the EDC system, refer to the procedures outlined 
above for initial reporting of SAEs. 
7.5 
Pregnancy Reporting 
Details of all pregnancies in female participants will be collected after the start of study 
intervention and until 90 days after the last dose of study intervention. 
• 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 [female 
participant or female partner of male participant (after obtaining the necessary signed informed 
consent from the female partner)] pregnancy. 

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• 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 patient will be followed to determine the outcome of the pregnancy. The Investigator will 
collect follow-up information on the 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 intervention 
by the Investigator will be reported to the Sponsor. While the Investigator is not obligated to 
actively seek this information in former study participants, he or she may learn of an SAE 
through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention. 
7.6 
Expedited Reporting 
The Sponsor/designee will report all relevant information about Suspected Unexpected Serious 
Adverse Reactions (SUSARs) that are fatal or life-threatening as soon as possible to the FDA, 
applicable competent authorities in all the Member States concerned, and the Central Ethics 
Committee, and in any case no later than 7 days after knowledge by the Sponsor/designee of such 
a case. Relevant follow-up information will subsequently be communicated within an additional 
8 days.  
All other SUSARs will be reported to the FDA, applicable competent authorities 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 investigational medicinal product. 
7.7 
Special Situation Reports 
Special Situation Reports include reports of overdose, misuse, abuse, medication error, and reports 
of adverse reactions associated with ALVR106. 
• 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 patient has taken additional dose(s) or the Investigator has reason to suspect that 
the patient has taken additional dose(s).  

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• Misuse: Refers to situations where the medicinal product is intentionally and inappropriately 
used not 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, patient, 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 patients missing doses of 
investigational product are not considered reportable as medication error. 
• 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 Situation 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 Situation 
Reports 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 All special situation events as described above must 
be reported on the Special Situations Report Form and faxed/emailed to Clinical Research 
Organization (CRO) Clinical Safety (contact information listed below) within 24 hours of 
knowledge of the event. All AEs associated with these Special Situations Report Form should be 
reported as adverse events or SAEs as well as recorded on the AE eCRF and/or the SAE report 
form. Details of the symptoms and signs, clinical management, and outcome should be provided, 
when available. 
Fax: 
 
 reporting line – USA: 
• Email:
 
• Fax: 
 
7.8 
Clinical Laboratory Evaluations 
Nasal swabs for viral load testing will be obtained as indicated in the Schedule of Procedures and 
sent to the central laboratory. 
Blood for clinical chemistry and hematology will be obtained as indicated in the Schedule of 
Procedures and sent to the central laboratory. See Appendix A for a complete list of analytes.  
Urine will be obtained as indicated in the Schedule of Procedures and sent to the central laboratory. 
See Appendix A for a complete list of analytes.  
A serum or urine pregnancy test will be performed for females of childbearing potential as 
indicated in the Schedule of Procedures and sent to the central or local laboratory. 

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Blood for PBMC and plasma collection for exploratory assays will be obtained as indicated in the 
Schedule of Procedures and sent to the central laboratory.  
7.9 
Vital Signs 
Vital sign measurements will include body temperature, heart rate, respiratory rate, and systolic 
and diastolic blood pressure and will be collected after resting for at least 5 minutes in the supine 
position as indicated in the Schedule of Procedures. 
7.10 
Electrocardiograms 
Standard 12-lead ECGs will be performed as indicated in the Schedule of Procedures. 
7.11 
Physical Examinations 
A complete physical examination will be performed at screening. Abbreviated physical exams will 
be performed at all subsequent visits.  
The complete physical examination will include: 
• General appearance 
• Head, eyes, ears, nose, and throat 
• Respiratory 
• Cardiovascular 
• Abdomen 
• Neurologic 
• Extremities 
• Dermatologic 
Abbreviated physical examinations will include a review of the respiratory and cardiovascular 
systems; skin and ears, nose, and throat; and a symptom-directed exam of all other systems. 
Physical examinations will be performed as indicated in Schedule of Procedures. 
If an abnormality noted on physical examination is considered by the Investigator to be clinically 
significant, then the abnormality will be recorded as part of the patient’s medical history if 
occurring prior to start of study treatment administration and as an adverse event if occurring after 
study treatment administration, where the finding represents a change from baseline. Any 
worsening of a baseline medical condition during the study should be recorded as an adverse event. 
7.12 
Graft Versus Host Disease 
Acute and chronic GVHD will be assessed as indicated in the Schedule of Procedures. If any 
patient develops GVHD, that patient may receive standard GVHD treatment at the discretion of 
the Investigator. 
7.12.1 
Acute Graft Versus Host Disease 
Staging and grading of acute GVHD will be reported using Mount Sinai Acute GVHD 
International Consortium guidelines (MAGIC) in Appendix B. For HCT patients, response to 

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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 B.40, 41 
7.12.2 
Chronic Graft Versus Host Disease (HCT Only) 
In HCT patients manifestations of chronic GVHD and response to treatment will be assessed as 
per National Institutes of Health Global Severity consensus guidelines for chronic GVHD as 
described in Appendix B.42,43 
7.13 
Infusion Site Evaluation 
Infusion site evaluation (includes pain, tenderness, erythema, swelling, and induration) will be 
performed as indicated in the Schedule of Procedures. On infusion days, injection site evaluation 
will be performed pre-dose and at 1 hour post-dose. 
7.14 
Post-Infusion Monitoring 
Post-infusion monitoring will be performed as indicated in the Schedule of Procedures. Patients 
will be monitored closely and must remain in the clinic for 1 hour after the end of each infusion. 
Vital signs and pulse oximetry will be measured at the end of the infusion (+/- 5 minutes), and at 
15 minutes (+/- 5 minutes), 30 minutes (+/- 10 minutes), 45 minutes (+/- 15 minutes), and 60 
minutes (+/- 15 minutes) after the end of the infusion. Data will be recorded on the eCRF. Post-
infusion monitoring should be completed for all infusions of study treatment. 

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8 
STATISTICAL CONSIDERATION 
This section provides the key details of the statistical analyses to be performed using data 
captured according to this protocol. A complete Statistical Analysis Plan (SAP) describing all 
planned analyses will be finalized prior to database lock. 
8.1 
Analysis Populations 
8.1.1 
Intent-to-Treat Population 
The Intent-to-Treat (ITT) Population will include all randomized patients regardless of whether 
the patient receives ALVR106 or placebo. The ITT population will be used for listings. 
8.1.2 
Safety Population 
The Safety Population will include all randomized patients who receive any amount of ALVR106 
or placebo. All safety and efficacy analyses will be based on the Safety Population.   
8.2 
Statistical Methods 
Data from Part A, and Part B of the study will be summarized and analyzed separately.  
Within each Part, placebo patients will be pooled. Pooling of the placebo patients between the 
cohorts provides a control group to better evaluate both safety and efficacy in this patient 
population, for which very little natural history exists.  This will allow an informed decision on 
dose and safety. 
8.2.1 
Analysis of Efficacy Endpoints 
The efficacy endpoints are described in Section 6.1. All the efficacy analyses will be performed 
using descriptive statistics by treatment group based on the Analysis Population.  
Categorical data will generally be summarized with counts and percentages of patients. Continuous 
data will generally be summarized with descriptive statistics, including the number of non-missing 
values, mean, median, standard deviation, minimum, and maximum. For time-to-event variables, 
the Kaplan-Meier method will be used to estimate the median time (days) and its 95% confidence 
interval. 
8.2.2 
Analysis of Safety Endpoints 
The safety endpoints are described in Section 7.1. All the safety data will be summarized by 
treatment group based on the Safety Population. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities. A TEAE is 
defined as an adverse event with a start date and time on or after the first dose of study treatment 
to the last dose of study drug plus 12 weeks. Treatment-emergent adverse events will be 
summarized by System Organ Class and Preferred Term and further by severity (according to the 
NCI CTCAE v5.0) and relationship to study treatment. Summaries will include all TEAEs, TEAEs 
by relationship, TEAEs by severity, serious TEAEs, TEAEs leading to study drug discontinuation. 
The incidence of AESI and the corresponding 95% exact binomial confidence intervals will be 
presented by treatment group. All AEs and DLTs will be listed by patient. 

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Descriptive statistics will be provided for relevant laboratory and vital sign data. Abnormal 
laboratory results will be graded according to NCI CTCAE v5.0, if applicable, except changes in 
respiratory status and imaging which will be graded using the Radiation Therapy Oncology Group 
lung toxicity scale (Table 1). A shift table, presenting the 2-way frequency tabulation for baseline 
and the worst post-baseline grade according to NCI CTCAE, may be provided for selected clinical 
laboratory tests. 
8.2.3 
Interim Analysis 
The SRC will review the cumulative safety and available efficacy data from each previous 
cohorts to recommend dose level and regimen for the subsequent cohorts.  
8.2.4 
Safety Review Committee 
An independent SRC will be convened for this study to routinely monitor safety. The SRC will 
consist of an external chair and two additional independent experts in the field, at least one of the 
members will be a transplant physician and at least one member will be an infectious disease 
expert. The SRC will regularly review emerging safety data and will conduct both open and closed 
meetings. Should any safety issues require review by the SRC, an emergency meeting will be 
scheduled within 72 hours. Further dosing will be stopped until the SRC makes an assessment.  
Based on routine safety reviews, the SRC may recommend escalating the dose as planned, 
recommend an intermediate dose, recommend expansion of the current cohort, recommend 
stopping dose escalation (Part A), or stop the study.  
In addition, the SRC will make a recommendation for the RP2D and starting enrollment of Part B.  
The Sponsor will determine the final RP2D based on SRC recommendation and after review of all 
available relevant safety and efficacy data through at least Day 28 following the first ALVR106 
or placebo infusion.  
Reference the SRC Charter for additional information.  
8.2.5 
Sample Size Determination 
No formal sample size determination was performed due to the exploratory nature of this study. 
The sample size has been set for an initial assessment of the safety and antiviral activity of 
ALVR106. 
For the Part A dose escalation portions of the study, approximately 16 to 32 patients will be 
randomized. The actual number of patients randomized will depend on the safety profile for each 
cohort and when the MTD is reached. 
For Part B RP2D cohort expansion portion of the study, a total of approximately 45 patients will 
be randomized.  

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9 
DATA MANAGEMENT AND RECORD KEEPING 
9.1 
Data Management 
9.1.1 
Data Handling 
Data will be recorded at the site on eCRFs and reviewed by the Clinical Research Associate (CRA) 
during monitoring visits. The CRAs will verify data recorded in the EDC system with source 
documents. All corrections or changes made to any study data must be appropriately tracked in an 
audit trail in the EDC system. An eCRF will be considered complete when all missing, incorrect, 
and/or inconsistent data has been accounted for. 
9.1.2 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory requirements. 
9.1.3 
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 CFR Part 11 and other appropriate 
international regulations. All passwords will be strictly confidential. 
9.1.4 
Medical Information Coding 
For medical information, the following thesauri will be used: 
• Medical Dictionary for Regulatory Activities (latest) for medical history and adverse events 
• World Health Organization Drug Dictionary for prior and concomitant medications 
9.1.5 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the investigative site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 
9.2 
Record Keeping 
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 is defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 
to further store such records.  

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9.3 
End of Study 
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last patient in the study. 
 

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10 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL  
10.1 
Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human patients. Compliance 
with this standard provides public assurance that the rights, safety, and well-being of study patients 
are protected, consistent with the principles that have their origin in the Declaration of Helsinki, 
and that the clinical study data are credible. 
10.2 
Institutional Review Board/Independent Ethics Committee 
10.2.1 
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, Investigator’s Brochure, informed consent form (ICF), 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. 
Federal regulations and International Council for Harmonisation (ICH) Guidelines require that 
approval be obtained from an IRB prior to participation of patients in research studies. Prior to 
study onset, the protocol, any protocol amendments, ICFs, advertisements to be used for patient 
recruitment, and any other written information regarding this study to be provided to a patient or 
patient’s legal guardian must be approved by the IRB. 
No drug will be released to the site for dosing until written IRB authorization has been received 
by the Sponsor. 
10.2.2 
Independent Ethics Committee 
It is the responsibility of the Sponsor or their designee (ie, Medpace) to obtain the approval of the 
responsible ethics committees according to the national regulations.  
The study will only start in the respective sites once the respective committee’s written approval 
has been given. 
10.3 
Informed Consent 
The ICF and any changes to the ICF 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 a parent or legal guardian) 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 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 will be given to the patient (or a parent 
or legal guardian). 

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10.4 
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, 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, Investigator’s Brochure, 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 is entered 
by the site, the CRA will review the data for safety information, completeness, accuracy, and 
logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
Investigators. The Investigator and his/her staff will be expected to cooperate with the monitor and 
provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-specific monitoring log. 
10.5 
Disclosure of Data 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB as appropriate. Patients or their legal 
representatives may request their medical information be given to their personal physician or other 
appropriate medical personnel responsible for their welfare. 
Patient medical information obtained during the study is confidential and disclosure to third parties 
other than those noted above is prohibited. 
10.6 
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, 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.   

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10.7 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 
10.8 
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. 
10.9 
Insurance and Indemnity 
In accordance with the relevant national regulations, the Sponsor has taken out patient liability 
insurance for all patients who have given 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. 
10.10 
Legal Aspects 
The clinical study will be submitted to the relevant national competent authorities in all 
participating countries to achieve a clinical trial authorization (CTA). 
The study will commence (ie, initiation of study centers) when the CTA and favorable Ethics 
opinion have been received. 

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11 
STUDY ADMINISTRATIVE INFORMATION 
11.1 
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. 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. 

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12 
REFERENCES 
 
1. Vasileiou S, Turney AM, Kuvalekar M, et al. Rapid generation of multivirus-specific 
T lymphocytes for the prevention and treatment of respiratory viral infections. 
Haematologica. 2019. doi: 10.3324/haematol.2018.206896. 
2. Billings JL, Hertz MI, Wendt CH. Community respiratory virus infections following lung 
transplantation. Transpl Infect Dis. 2001; 3:138–148. doi: 10.1034/j.1399-3062.2001. 
003003138.x 
3. Palmer SM, Jr, Henshaw NG, Howell DN, Miller SE, Davis RD, Tapson VF. Community 
respiratory viral infection in adult lung transplant recipients. Chest. 1998; 113:944–950. 
doi: 10.1378/chest.113.4.944.   
4. Vu DL, Bridevaux PO, Aubert JD, Soccal PM, Kaiser L. 2011. Respiratory viruses in lung 
transplant recipients: a critical review and pooled analysis of clinical studies. Am J 
Transplant 2011:1071–1078. https://doi.org/10.1111/j.1600-6143.2011.03490.x. 
5. McCurdy LH, Milstone A, Dummer S. Clinical features and outcomes of paramyxoviral 
infection in lung transplant recipients treated with ribavirin. J Heart Lung 
Transplant. 2003; 22:745–753. doi: 10.1016/S1053-2498(02)00569-7.   
6. 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host. 
Rubin et al. CID 2014:58 (1February).  
7. Vaccination of solid organ transplant candidates and recipients: Guidelines from the 
American society of transplantation infectious diseases community of practice. 
AUDanziger-Isakov L, Kumar D, AST ID Community of Practice SOClin Transplant. 
2019;33(9): e13563. Epub 2019 Jun 5.  
8. Walter EA, Greenberg PD, Gilbert MJ, et al. Reconstitution of cellular immunity against 
cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones 
from the donor. N Engl J Med. 1995;333(16):1038-1044. 
9. Peggs KS, Verfuerth S, Pizzey A, et al. Adoptive cellular therapy for early 
cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific 
T-cell lines. Lancet. 2003;362(9393):1375-1377. 
10. Peggs KS, Thomson K, Samuel E, et al. Directly selected cytomegalovirus-reactive donor 
T cells confer rapid and safe systemic reconstitution of virus-specific immunity following 
stem cell transplantation. Clin Infect Dis. 2011;52(1):49-57. 
11. Mackinnon S, Thomson K, Verfuerth S, et al. Adoptive cellular therapy for 
cytomegalovirus infection following allogeneic stem cell transplantation using 
virus-specific T cells. Blood Cells Mol Dis. 2008;40(1):63-67. 
12. Einsele H, Roosnek E, Rufer N, et al. Infusion of cytomegalovirus (CMV)-specific 
T cells for the treatment of CMV infection not responding to antiviral chemotherapy. 
Blood. 2002;99(11):3916-3922. 
13. Feuchtinger T, Opherk K, Bethge WA, et al. Adoptive transfer of pp65-specific T cells 
for the treatment of chemorefractory cytomegalovirus disease or reactivation after 
haploidentical and matched unrelated stem cell transplantation. Blood. 
2010;116(20):4360-4367. 
 
 

AlloVir 
Clinical Study Protocol P-106-001 
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Version 5.0,  19 May 2022 
72 
 
14. Schmitt A, Tonn T, Busch DH, et al. Adoptive transfer and selective reconstitution of 
streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in 
patients after allogeneic peripheral blood stem cell transplantation. Transfusion. 
2011;51(3):591-599. 
15. Cobbold M, Khan N, Pourgheysari B, et al. Adoptive transfer of 
cytomegalovirus-specific CTL to stem cell transplant patients after selection by 
HLA-peptide tetramers. J Exp Med. 2005;202(3):379-386. 
16. Rooney CM, Smith CA, Ng CY, et al. Use of gene-modified virus-specific T 
lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 
1995;345(8941):9-13. 
17. Heslop HE, Ng CY, Li C, et al. Long-term restoration of immunity against Epstein-Barr 
virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. 
Nat Med. 1996;2(5):551-555. 
18. Leen AM, Christin A, Myers GD, et al. Cytotoxic T lymphocyte therapy with donor 
T cells prevents and treats adenovirus and Epstein-Barr virus infections after 
haploidentical and matched unrelated stem cell transplantation. Blood. 
2009;114(19):4283-4292. 
19. Leen AM, Myers GD, Sili U, et al. Monoculture-derived T lymphocytes specific for 
multiple viruses expand and produce clinically relevant effects in immunocompromised 
individuals. Nat Med. 2006;12(10):1160-1166. 
20. Gerdemann U, Katari UL, Papadopoulou A, et al. Safety and clinical efficacy of 
rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV 
infections after allogeneic hematopoietic stem cell transplant. Mol Ther. 
2013;21(11):2113-2121. 
21. Papadopoulou A, Gerdemann U, Katari UL, et al. Activity of broad-spectrum T cells as 
treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. 
Sci Transl Med. 2014;6(242):242ra83. 
22. Feuchtinger T, Matthes-Martin S, Richard C, et al. Safe adoptive transfer of 
virus-specific T-cell immunity for the treatment of systemic adenovirus infection after 
allogeneic stem cell transplantation. Br J Haematol. 2006;134(1):64-76. 
23. Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of epstein-barr virus (EBV) nuclear 
antigen 1-specific t cells as treatment for EBV reactivation and lymphoproliferative 
disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013;31(1):39-48. 
24. Heslop HE, Slobod KS, Pule MA, et al. Long-term outcome of EBV-specific T-cell 
infusions to prevent or treat EBV-related lymphoproliferative disease in transplant 
recipients. Blood. 2010;115(5):925-935. 
25. Bollard CM, Heslop HE. T cells for viral infections after allogeneic hematopoietic stem 
cell transplant. Blood. 2016;127(26):3331-3340. 
26. O’Reilly, Prockop S, Hasan AN, et al. Virus-specific T-cell banks for 'off the shelf' 
adoptive 
therapy 
of 
refractory 
infections. 
Bone 
Marrow 
Transplant. 
2016;51(9):1163-1172. 
27. Haque T, Wilkie GM, Jones MM, et al. Allogeneic cytotoxic T-cell therapy for 
EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 
multicenter clinical trial. Blood. 2007;110(4):1123-1131. 
28. Haque T, Wilkie GM, Taylor C, et al. Treatment of Epstein-Barr-virus-positive 
 

AlloVir 
Clinical Study Protocol P-106-001 
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73 
 
post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic 
cytotoxic T cells. Lancet. 2002;360(9331):436-442. 
29. Vickers MA, Wilkie GM, Robinson N, et al. Establishment and operation of a Good 
Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific 
cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease. 
Br J Haematol. 2014;167(3):402-410. 
30. Leen AM, Bollard CM, Mendizabal AM, et al. Multicenter study of banked third-party 
virus-specific T cells to treat severe viral infections after hematopoietic stem cell 
transplantation. Blood. 2013;121(26):5113-5123. 
31. Haque T et all. Allogeneic cytotoxic T-cell therapy for EBV-positive post transplantation 
lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood, 2007; 
110 (4) 
32. Martits-Chalangari K, Spak CW, Medhat A, Killian A, Fisher TL, Atillasoy E, Marshall 
WL, McNeel D, Miller MD, Mathai SK, Gottlieb, RL. ALVR109, an off-the-shelf partially 
HLA matched SARS-CoV-2–specific T cell therapy, to treat refractory severe COVID-19 
pneumonia in a heart transplant patient: Case report. American Journal of Transplantation.  
15 December 2021.  https://doi.org/10.1111/ajt.16927 
33. Hill L, Alousi A, Kebriaei P, et al. New and emerging therapies for acute and chronic graft 
versus host disease. Ther Adv Hematol. 2018;9(1):21-46. doi:10.1177/2040620717741860 
34. Stefanska I, Romanowska M, Donevski S, Gawryluk D, Brydak LB. Co-infections with 
influenza and other respiratory viruses. Adv Exp Med Biol. 2013;756:291-301. 
doi:10.1007/978-94-007-4549-0_36 
35. Tzannou I, Papadopoulou A, Naik S, et al. Off-the-shelf virus-specific T cells to treat BK 
virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, and adenovirus 
infections after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 
2017;35(31):3547-3557. 
36. Fisher C.E., Preiksaitis C.M., Lease E.D. Symptomatic respiratory virus infection and 
chronic lung allograft dysfunction. Clin Infect Dis. 2016;62(3):313–319. 
37. Ljungman P., Ward K.N., Crooks B.N. Respiratory virus infections after stem cell 
transplantation: a prospective study from the Infectious Diseases Working Party of the 
European 
Group 
for 
Blood 
and 
Marrow 
Transplantation. Bone 
Marrow 
Transplant. 2001;28(5):479–484  
38. McCurdy LH, Milstone A, Dummer S. Clinical features and outcomes of paramyxoviral 
infection in lung transplant recipients treated with ribavirin. J Heart Lung 
Transplant. 2003; 22:745–753. doi: 10.1016/S1053-2498(02)00569-7.  
39. https://www.who.int/health-topics/severe-acute-respiratory-syndrome#tab=tab_1. 
Accessed on March 25, 2022. 
40. 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.  
41. 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 
 

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06 July 2020. 
42. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus 
development project on criteria for clinical trials in chronic graft-versus-host-disease: I. 
The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 
2015;21(3):389-401.e1.  
43. Lee SJ, Wolff D, Kitko C, et al. Measuring therapeutic response in chronic 
graft-versus-host disease. National Institutes of Health consensus development project on 
criteria for clinical trials in chronic graft-versus-host disease: IV. The 2014 response 
criteria working group report. Biol Blood Marrow Transplant. 2015;21(6):984-999.  
 

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APPENDIX A:  CLINICAL LABORATORY ANALYTES 
Standard Safety Chemistry Panel 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
Direct bilirubin 
Estimated glomerular filtration rate 
Gamma-glutamyl transferase 
Glucose 
Inorganic phosphorus 
Lactate dehydrogenase 
Lipase 
Potassium 
Sodium 
Total bilirubin 
Total protein 
Uric acid 
 
 
Hematology 
Hematocrit 
Hemoglobin 
Platelets 
Red blood cell count 
White blood cell count and differential [1] 
 
1. Manual microscopic review is performed only if white blood cell count and/or differential values 
are out of reference range. 
 
Urinalysis 
Bilirubin 
Blood 
Glucose 
Ketones 
Leukocyte esterase 
Urobilinogen 
Nitrite 
pH 
Protein 
Specific gravity 
Microscopy  (Microscopy is always performed (cannot be replaced with a dipstick analysis). 
Pregnancy Tests (Female patients of childbearing potential only) 
Serum 
Urine human chorionic gonadotropin 
 
 
Viral Load (Measured by nasal swab) 
Human metapneumovirus 
Parainfluenza virus 
SARS-CoV-2 
Influenza 
Respiratory syncytial virus 
 
 
Blood Sample for Viremia Assessment and Donor specific antibody (Stored for possible 
analysis). Bank PBMCs for virus-specific immunity and ALVR106 persistence, and plasma 
for cytokine evaluation (Stored for possible analysis) 

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APPENDIX B:  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 1: Stage 1 to 2 skin without liver, upper GI, or lower GI involvement.  
Grade 2: Stage 3 rash and/or Stage 1 liver and/or Stage 1 upper GI and/or Stage 1 lower GI. 
Grade 3: 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 4: 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; MAGIC = Mount Sinai Acute GVHD 
International Consortium. 
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 06 July 2020. 
 
For HCT only: 
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(3):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 C:  CYTOKINE RELEASE SYNDROME GRADING SCALE 
AND MANAGEMENT 
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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CRS = cytokine release syndrome; O2 = oxygen. 
Source: Adapted from Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine 
release syndrome. Blood. 2014;124(2):188-195. 

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APPENDIX D:  PATIENT-REPORTED ASSESSMENT OF RESPIRATORY 
CLINICAL SYMPTOMS  
This assessment tool consists of four questions related to your respiratory (breathing) symptoms. 
Every time you are asked to evaluate your symptoms of cough, breathlessness (difficulty breathing, 
shortness of breath), wheezing, and sputum (phlegm, mixture of saliva and mucous) production by 
scoring them from 0 to 3 based on the following definition: 
 
0 
1 
2 
3 
(none) 
(mild) 
(moderate) 
(severe) 
 
discomfort noticed 
but no disruption of 
normal daily activity 
discomfort sufficient 
to reduce or affect 
normal daily activity 
discomfort with 
inability to perform 
normal daily 
activities 
 
In the last 24 hours: 
Date:  
 
 
Visit:  
 
 
Time: 
Respiratory Symptoms 
Please mark only one “X” in the cell underneath the response. 
1. Cough: How severe was your cough? 
0 (none) 
1 (mild) 
2 (moderate) 
3 (severe) 
 
 
 
 
2. Breathlessness: How severe was your breathlessness? 
 
0 (none) 
1 (mild) 
2 (moderate) 
3 (severe) 
 
 
 
 
3. Wheezing: How severe was your wheezing? 
0 (none) 
1 (mild) 
2 (moderate) 
3 (severe) 
 
 
 
 
4. Sputum production: How severe was your sputum production? 
0 (none) 
1 (mild) 
2 (moderate) 
3 (severe) 
 
 
 
 
5. Fever: What was your highest body temperature? 
0 (normal body 
temperature) 
1 (mild) 
2 (moderate) 
3 (severe) 
<99°F 
>100°F 
>101°F 
>103°F 
 

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SUMMARY OF CHANGES 
Please refer to the attached Summary of Changes document entitled:  
Summary of Changes: 
Protocol Number P-106-001  
Amendment Number 3 (Version 4.0) to  
Amendment Number 4 (Version 5.0)  
 

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20-May-2022 15:47:19 GMT+0000