Posoleucel (ALVR105) for the Treatment of Adenovirus Infe... | NCT05179057

Label	Type	Description	Intervention Names
Posoleucel + SoC	Experimental	Posoleucel + SOC; then placebo + SOC for patients who meet optional protocol-defined crossover criteria	Drug: Posoleucel
Placebo + SoC	Placebo Comparator	Placebo + SOC; then Posoleucel + SOC for patients who meet optional protocol-defined crossover criteria	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Posoleucel	Drug	Administered as 2-4 milliliter infusion, visually identical to placebo	Posoleucel + SoC

Measure	Description	Time Frame
Number of Participants With Undetectable Adenovirus Infection	Viral load of adenovirus was measured at the central laboratory using quantitative polymerase chain reaction (qPCR) from blood and stool samples at each study visit and on Day 29 from a nasopharyngeal swab. There was a 14-day window for participants who crossed over from posoleucel to placebo; and for participants who crossed over from placebo to posoleucel, the pre-dose cross-over Day 1 viral load was used. Participants missing the primary endpoint but having undetectable viremia before Day 29 and after Day 43 were imputed as successes. Undetectable adenovirus viremia was less than the lower limit of quantification (LLOQ).	Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion)
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	A TEAE was defined as an adverse event (AE) with a start date and time on or after the first dose of study treatment. A serious AE (SAE) was an AE that met at least one of the following serious criteria: fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other important medical event. TEAEs of special interest (AESI) included acute or chronic graft versus host disease, cytokine release syndrome, infusion-related reactions, and graft failure or rejection. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator.	Up to 34 weeks

Measure	Description	Time Frame
Number of Participants With Overall Disease Progression		From Day 29 up to Week 10
Area Under the Curve (AUC) Adenovirus Viral Load		Pre-dose and Day 29
Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29

Facility	Status	City	State	ZIP	Country	Contacts
MD Anderson Cancer Center		Gilbert	Arizona	85234	United States
Phoenix Children's Hospital

PubMed Identifier	Type	Citation	Retractions
38597860	Derived	Vasileiou S, Kuvalekar M, Velazquez Y, Watanabe A, Leen AM, Gilmore SA. Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients. Cytotherapy. 2024 Aug;26(8):869-877. doi: 10.1016/j.jcyt.2024.03.012. Epub 2024 Mar 19.

ID	Title	Description
FG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 30, 2023	Apr 12, 2024

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Undetectable Adenovirus Infection

Viral load of adenovirus was measured at the central laboratory using quantitative polymerase chain reaction (qPCR) from blood and stool samples at each study visit and on Day 29 from a nasopharyngeal swab. There was a 14-day window for participants who crossed over from posoleucel to placebo; and for participants who crossed over from placebo to posoleucel, the pre-dose cross-over Day 1 viral load was used. Participants missing the primary endpoint but having undetectable viremia before Day 29 and after Day 43 were imputed as successes. Undetectable adenovirus viremia was less than the lower limit of quantification (LLOQ).

The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of posoleucel or placebo. Only participants in the mITT population who completed through Day 29 or discontinued early were included.

Posted

Count of Participants

Participants

Day 29 through Day 43 (Day 29 + 14 days; up to 43 days post-first infusion)

ID	Title	Description
OG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
OG001	Placebo, Then Posoleucel	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to posoleucel treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.

Units	Counts
Participants	OG00025 OG00121

Title

Denominators

Categories

Title	Measurements
	OG00011 OG0019

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Odds Ratio (OR)	0.98			2-Sided	95	0.26	3.69			Posoleucel versus Placebo		Superiority	A logistic regression model included treatment, level of viremia at baseline (≥10,000 copies/mL or <10,000 copies/mL adenovirus DNA), age (≥12 years or <12 years), and absolute lymphocyte counts at baseline. The null hypothesis is that the true percentage for posoleucel plus SoC is less than or equal to the true percentage for placebo plus SoC, and the alternative hypothesis is that it is greater.

Primary

Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

A TEAE was defined as an adverse event (AE) with a start date and time on or after the first dose of study treatment. A serious AE (SAE) was an AE that met at least one of the following serious criteria: fatal, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other important medical event. TEAEs of special interest (AESI) included acute or chronic graft versus host disease, cytokine release syndrome, infusion-related reactions, and graft failure or rejection. Treatment-related refers to the assessment of a relationship between study treatment and the event by the investigator.

The safety population included all participants who received any amount of posoleucel or placebo and had at least one post-treatment safety assessment.

Posted

Count of Participants

Participants

Up to 34 weeks

ID	Title	Description
OG000	Posoleucel (Primary Study Period)	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days, during the Primary Study Period.
OG001	Placebo (Primary Study Period)	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days, during the Primary Study Period.

Secondary

Number of Participants With Overall Disease Progression

Data not collected due to early termination after Data and Safety Monitoring Board (DSMB) futility analysis concluded the study was unlikely to meet its primary endpoint.

Posted

From Day 29 up to Week 10

ID	Title	Description
OG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
OG001	Placebo, Then Posoleucel	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to posoleucel treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.

Secondary

Area Under the Curve (AUC) Adenovirus Viral Load

Data not collected due to early termination after DSMB futility analysis concluded the study was unlikely to meet its primary endpoint.

Posted

Pre-dose and Day 29

ID	Title	Description
OG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
OG001	Placebo, Then Posoleucel	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to posoleucel treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.

Secondary

Number of Participants Who Achieved Adenovirus Viremia <400 Copies/mL at Day 29

Data not collected due to early termination after DSMB futility analysis concluded the study was unlikely to meet its primary endpoint.

Posted

Day 29

ID	Title	Description
OG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
OG001	Placebo, Then Posoleucel	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to posoleucel treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.

Secondary

Time to Undetectable Adenovirus Viremia (Less Than LLOQ)

Data not collected due to early termination after DSMB futility analysis concluded the study was unlikely to meet its primary endpoint.

Posted

Pre-dose to 34 weeks

ID	Title	Description
OG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
OG001	Placebo, Then Posoleucel	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to posoleucel treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.

Secondary

Number of Participants With Adenovirus Disease Recurrence

Data not collected due to early termination after DSMB futility analysis concluded the study was unlikely to meet its primary endpoint.

Posted

34 weeks

ID	Title	Description
OG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
OG001	Placebo, Then Posoleucel	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to posoleucel treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG0030 affected4 at risk
COVID-19	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Candida infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Clostridium difficile colitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Cryptosporidiosis infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Cytomegalovirus colitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Cytomegalovirus infection reactivation	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Device related infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Enterocolitis infectious	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Escherichia pyelonephritis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Gastroenteritis rotavirus	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Human herpesvirus 6 infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Localised infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Pancreatitis viral	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Parainfluenzae virus infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Parotitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Phlebitis infective	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Pneumococcal bacteraemia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Respiratory syncytial virus infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Sepsis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0021 affected5 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Sinusitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Pyrexia	General disorders	MedDRA 25.1	Systematic Assessment	EG0004 affected28 at risk EG0013 affected23 at risk EG0020 affected5 at risk EG003
Asthenia	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Disease progression	General disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Influenza like illness	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Chronic graft versus host disease in intestine	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Acute graft versus host disease in intestine	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Acute graft versus host disease in skin	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Chronic graft versus host disease	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Chronic graft versus host disease in lung	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Chronic graft versus host disease oral	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Graft versus host disease in gastrointestinal tract	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Haemophagocytic lymphohistiocytosis	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Acute graft versus host disease	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Graft versus host disease	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Thrombotic microangiopathy	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Immune-mediated cytopenia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Renal tubular disorder	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Pneumomediastinum	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Capillary leak syndrome	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Acute hepatic failure	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Weight decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Leukaemia recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Seizure	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Cerebral haemorrhage	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Autoimmune haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
COVID-19	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG0031 affected4 at risk
Rhinovirus infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0013 affected23 at risk EG0020 affected5 at risk EG003
BK virus infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Candida infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Pneumonia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Adenovirus infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Cytomegalovirus infection reactivation	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0013 affected23 at risk EG0021 affected5 at risk EG003
Cytomegalovirus viraemia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Gastroenteritis adenovirus	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Sepsis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Adenoviral hepatitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Enterovirus infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Epstein-Barr virus infection reactivation	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Klebsiella bacteraemia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Epstein-Barr viraemia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Klebsiella infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Viral rhinitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0008 affected28 at risk EG0014 affected23 at risk EG0020 affected5 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0005 affected28 at risk EG0014 affected23 at risk EG0021 affected5 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0006 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0006 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0013 affected23 at risk EG0020 affected5 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Platelet count decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0013 affected23 at risk EG0021 affected5 at risk EG003
Weight decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Blood bicarbonate decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Blood creatinine increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0021 affected5 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Lipase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Enterobacter test positive	Investigations	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0009 affected28 at risk EG0016 affected23 at risk EG0021 affected5 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0005 affected28 at risk EG0013 affected23 at risk EG0020 affected5 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0012 affected23 at risk EG0021 affected5 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected23 at risk EG0021 affected5 at risk EG003
Hypervolaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0021 affected5 at risk EG003
Iron overload	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Hypermagnesaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Pyrexia	General disorders	MedDRA 25.1	Systematic Assessment	EG00010 affected28 at risk EG0018 affected23 at risk EG0021 affected5 at risk EG003
Hyperammonaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Gait disturbance	General disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Asthenia	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected23 at risk EG0021 affected5 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0006 affected28 at risk EG0015 affected23 at risk EG0022 affected5 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0011 affected23 at risk EG0021 affected5 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0021 affected5 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Acute graft versus host disease in intestine	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0013 affected23 at risk EG0020 affected5 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0013 affected23 at risk EG0020 affected5 at risk EG003
Acute graft versus host disease in skin	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Hypogammaglobulinaemia	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Graft versus host disease	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Graft versus host disease in liver	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Glycosuria	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Hypertension	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0004 affected28 at risk EG0011 affected23 at risk EG0020 affected5 at risk EG003
Phimosis	Congenital, familial and genetic disorders	MedDRA 25.1	Systematic Assessment	EG0004 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Vision blurred	Eye disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Orbital haematoma	Eye disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected23 at risk EG0020 affected5 at risk EG003
Somnolence	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Traumatic haematoma	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0020 affected5 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected23 at risk EG0021 affected5 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 25.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected23 at risk EG0021 affected5 at risk EG003

ID	Term
D004266	DNA Virus Infections
D014777	Virus Diseases
D007239	Infections

ID	Title	Description
BG000	Posoleucel, Then Placebo	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to placebo treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
BG001	Placebo, Then Posoleucel	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days. The Primary Study Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up. Eligible participants who experienced progression to active target organ disease or progression of existing target organ disease could cross-over to posoleucel treatment between Day 29 and Week 10. In the Cross-Over Period, participants received 2 sequential infusions of placebo, separated by 14 ± 3 days. The Cross-over Period included a 4-week efficacy evaluation followed by a 20-week safety follow-up.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Posoleucel (Primary Study Period)	Participants were randomized to receive 2 sequential infusions of posoleucel, separated by 14 ± 3 days, during the Primary Study Period.	2	28	16	28	27	28
EG001	Placebo (Primary Study Period)	Participants were randomized to receive 2 sequential infusions of placebo, separated by 14 ± 3 days, during the Primary Study Period.	1	23	16	23	23	23
EG002	Posoleucel (Cross-over Period)	Participants were randomized to receive 2 sequential infusions of placebo in the Primary Study Period and were eligible to cross-over between Day 29 and Week 10. Participants received posoleucel during the Cross-over Period.	0	5	3	5	5	5
EG003	Placebo (Cross-over Period)	Participants were randomized to receive 2 sequential infusions of posoleucel in the Primary Study Period and were eligible to cross-over between Day 29 and Week 10. Participants received placebo during the Cross-over Period.	1	4	1	4	3	4