Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA... | NCT01380990

Name	Class
Orchard Therapeutics	INDUSTRY

Label	Type	Description	Intervention Names
Gene Therapy	Experimental	Infusion of autologous EFS-ADA LV CD34+ cells	Genetic: Infusion of autologous EFS-ADA LV CD34+ cells Drug: Busulfan Drug: Peg-Ada
Historical Control Group	Other	Historical data from ADA-SCID patients who were treated with Hematopoietic Stem Cell Transplantation (HSCT)	Other: Haematopoietic Stem Cell Transplantation (HSCT)

Name	Type	Description	Arm Group Labels	Other Names
Infusion of autologous EFS-ADA LV CD34+ cells	Genetic	Autologous EFS-ADA LV CD34+ cells (OTL-101*) are infused intravenously	Gene Therapy

Measure	Description	Time Frame
Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)	Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101* or HSCT	12 months
Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)	Event-free survival is defined as the percentage of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.	12 months
Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils)	Engraftment of transduced cells was assessed using vector gene marking in granulocytes (neutrophils)	36 months
VCN in Peripheral Blood Mononuclear Cells (PBMCs)	Engraftment of transduced cells was assessed using vector gene marking in PBMCs	36 months
VCN in CD3+ T Cells	Engraftment of transduced cells was assessed using vector gene marking	36 months
VCN in CD19+ B Cells	Engraftment of transduced cells was assessed using vector gene marking in CD19+ B Cells	36 months
Change From Baseline in CD3+ T Cell Counts (1 Year)	Immune reconstitution was assessed by change in CD3+ T Cell counts over time.

Measure	Description	Time Frame
OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)	Overall survival (OS) is defined as the percentage of subjects alive at 36 months post- treatment with OTL-101* or HSCT	36 months
EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)

Name	Affiliation	Role
Claire Booth, Dr	Great Ormond Street Hospital NHS Foundation Trust	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Great Ormond Street Hospital for Children NHS Foundation Trust		London		WC1N 3JH	United Kingdom

PubMed Identifier	Type	Citation	Retractions
33974366	Derived	Kohn DB, Booth C, Shaw KL, Xu-Bayford J, Garabedian E, Trevisan V, Carbonaro-Sarracino DA, Soni K, Terrazas D, Snell K, Ikeda A, Leon-Rico D, Moore TB, Buckland KF, Shah AJ, Gilmour KC, De Oliveira S, Rivat C, Crooks GM, Izotova N, Tse J, Adams S, Shupien S, Ricketts H, Davila A, Uzowuru C, Icreverzi A, Barman P, Campo Fernandez B, Hollis RP, Coronel M, Yu A, Chun KM, Casas CE, Zhang R, Arduini S, Lynn F, Kudari M, Spezzi A, Zahn M, Heimke R, Labik I, Parrott R, Buckley RH, Reeves L, Cornetta K, Sokolic R, Hershfield M, Schmidt M, Candotti F, Malech HL, Thrasher AJ, Gaspar HB. Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency. N Engl J Med. 2021 May 27;384(21):2002-2013. doi: 10.1056/NEJMoa2027675. Epub 2021 May 11.

ID	Title	Description
FG000	Gene Therapy	Infusion of autologous EF1αS-ADA (EFS-ADA) lentiviral vector (LV) mediated gene modification of autologous CD34+ cells Infusion of autologous EFS-ADA LV CD34+ cells: Autologous EFS-ADA LV CD34+ cells (OTL-101*) are infused intravenously Busulfan: Busulfan is used for non-myeloablative conditioning Polyethylene glycol-modified adenosine deaminase (PEG-ADA): PEG-ADA enzyme replacement therapy (ERT) is discontinued at Day +3- (-3/+15 days) after successful engraftment

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 28, 2017	Feb 19, 2021

ID	Title	Description
BG000	Gene Therapy	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
BG001	Historical Control Group	Complete HSCT historical control group consisting of ADA-SCID patients with any type of donor treated with HSCT at GOSH from 2000 to 2016 (referred to as the All HSCT Controls group)
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00020 BG00116 BG00236

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

Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)

Overall survival is defined as the percentage of subjects alive at 12 months post- treatment with OTL-101* or HSCT

Posted

Number

95% Confidence Interval

percentage of participants

12 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
OG002	HSCT Controls Without MRD	The primary efficacy population from the HSCT historical control cohort comprises ADA-SCID patients without a medically eligible Matched Related Donor (MRD) who were treated with HSCT at GOSH from 2000 to 2016. An MRD refers to either a matched sibling or family donor.
OG003	HSCT Controls With MRD	Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016
OG004	All HSCT Controls	Complete HSCT historical control group consisting of ADA-SCID patients with any type of donor treated with HSCT at GOSH from 2000 to 2016 (referred to as the All HSCT Controls group)

Units	Counts
Participants	OG00010 OG00120 OG0025 OG003

Title

Denominators

Categories

Title	Measurements
	OG000100(69.15 to 100) OG001100(83.16 to 100) OG002100(47.82 to 100) OG003

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 OG002	Percentage of patients alive at 1-year post-treatment in the historical control groups (without MRD) were compared to the percentage of study patients alive at 1-year post-treatment with OTL-101* (on-study). Results are reported as percentage difference in OS of historical control group from OTL-101* on-study subjects.					Difference in percentages	0			2-Sided								Superiority

Primary

Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)

Event-free survival is defined as the percentage of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.

Posted

Number

95% Confidence Interval

percentage of participants

12 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
OG002	HSCT Controls Without MRD	The primary efficacy population from the HSCT historical control cohort comprises ADA-SCID patients without a medically eligible MRD who were treated with HSCT at GOSH from 2000 to 2016. An MRD refers to either a matched sibling or family donor.
OG003	HSCT Controls With MRD

Primary

Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils)

Engraftment of transduced cells was assessed using vector gene marking in granulocytes (neutrophils)

Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant

Posted

Median

Full Range

copies/cell

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).

Units	Counts
Participants	OG000

Primary

VCN in Peripheral Blood Mononuclear Cells (PBMCs)

Engraftment of transduced cells was assessed using vector gene marking in PBMCs

Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant

Posted

Median

Full Range

copies/cell

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).

Units	Counts
Participants	OG000

Primary

VCN in CD3+ T Cells

Engraftment of transduced cells was assessed using vector gene marking

Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant

Posted

Median

Full Range

copies/cell

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).

Units	Counts
Participants	OG000

Primary

VCN in CD19+ B Cells

Engraftment of transduced cells was assessed using vector gene marking in CD19+ B Cells

Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VCN levels is not relevant

Posted

Median

Full Range

copies/cell

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).

Units	Counts
Participants	OG000

Primary

Change From Baseline in CD3+ T Cell Counts (1 Year)

Immune reconstitution was assessed by change in CD3+ T Cell counts over time.

Historical control groups/arms are not included in the analysis population for this outcome measure as CD3+ T cell count data was not collected due to the historical nature of the population

Posted

Geometric Mean

95% Confidence Interval

10e9 cells/L

12 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).

Units	Counts
Participants	OG000

Primary

Change From Baseline in CD3+ T Cell Counts (3 Years)

Immune reconstitution was assessed by change in CD3+ T Cell counts over time.

Historical control groups/arms are not included in the analysis population for this outcome measure as CD3+ T cell count data was not collected due to the historical nature of the population

Posted

Median

Full Range

10e9 cells/L

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).

Units	Counts
Participants	OG000

Primary

ADA Activity in Erythrocytes

ADA enzyme activity was assessed as a measure of successful engraftment of genetically modified Hematopoietic stem progenitor cells (HSPCs), as it marks sustained gene expression from the normal ADA transgene.

Posted

Median

Full Range

nmol/h/mg

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
OG002	HSCT Controls Without MRD	The primary efficacy population from the HSCT historical control cohort comprises ADA-SCID patients without a medically eligible MRD who were treated with HSCT at GOSH from 2000 to 2016. An MRD refers to either a matched sibling or family donor.
OG003	HSCT Controls With MRD	Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016

Primary

Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes

Decreased dATP levels coincide with increased ADA enzyme activity, detoxification was used as a marker of correction of the defective ADA gene. The threshold for detoxification was <100 μmol/L.

Posted

Median

Full Range

umol/L

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
OG002	HSCT Controls Without MRD	The primary efficacy population from the HSCT historical control cohort comprises ADA-SCID patients without a medically eligible MRD who were treated with HSCT at GOSH from 2000 to 2016. An MRD refers to either a matched sibling or family donor.
OG003	HSCT Controls With MRD	Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016

Primary

Frequency of Vector Integration Into Known Protooncogenes (3 Years)

Vector Integration Site Analysis (VISA) allowed determination of the distribution of vector integration sites in each subject's genome, as well as the relative clonal abundance. VISA was to be considered abnormal for a subject if, in 2 or more instances during the course of follow-up, a single integration site was found to represent >30% of the total integration sites detected.

There were no instances of clonal proliferation in the course of the 36 month follow-up for on-study and CUP subjects; hence, a detailed analysis of the frequency of clonal expansion associated with vector integration near proto-oncogenes was not generated.

Historical control groups/arms are not included in the analysis population for this outcome measure as these subjects did not receive gene therapy, and so measurement of VISA is not relevant

Posted

Number

% of integration in known protooncogenes

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).

Secondary

OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)

Overall survival (OS) is defined as the percentage of subjects alive at 36 months post- treatment with OTL-101* or HSCT

Posted

Number

95% Confidence Interval

percentage of participants

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
OG002	HSCT Controls Without MRD	The primary efficacy population from the HSCT historical control cohort comprises ADA-SCID patients without a medically eligible MRD who were treated with HSCT at GOSH from 2000 to 2016. An MRD refers to either a matched sibling or family donor.
OG003	HSCT Controls With MRD	Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016

Secondary

EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)

Posted

Number

95% Confidence Interval

percentage of participants

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
OG002	HSCT Controls Without MRD	The primary efficacy population from the HSCT historical control cohort comprises ADA-SCID patients without a medically eligible MRD who were treated with HSCT at GOSH from 2000 to 2016. An MRD refers to either a matched sibling or family donor.
OG003	HSCT Controls With MRD

Secondary

Infection Rate

The infections of interest in this study were severe infections or opportunistic infectious episodes, defined as infections requiring hospitalization or prolonging hospitalization and/or documented infections by opportunistic pathogens.

Posted

Number

Infection rate per person per year

36 months

ID	Title	Description
OG000	OTL-101* On-Study Subjects	The primary efficacy population for analysis consists of the on-study OTL-101*-treated subjects.
OG001	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101-treated subjects (on-study and CUP). The secondary efficacy population consists of all OTL-101-treated subjects (on-study and CUP).
OG002	HSCT Controls Without MRD	The primary efficacy population from the HSCT historical control cohort comprises ADA-SCID patients without a medically eligible MRD who were treated with HSCT at GOSH from 2000 to 2016. An MRD refers to either a matched sibling or family donor.
OG003	HSCT Controls With MRD

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Rhinitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG00015 events9 affected20 at risk EG0019 events5 affected10 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG00012 events7 affected20 at risk EG0017 events4 affected10 at risk
Otitis media	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0004 events3 affected20 at risk EG0012 events2 affected10 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0012 events2 affected10 at risk
Metapneumovirus infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0012 events2 affected10 at risk
Viral rash	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0012 events2 affected10 at risk
Ear infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0003 events2 affected20 at risk EG0012 events1 affected10 at risk
Device related infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected10 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected20 at risk EG0011 events1 affected10 at risk
Hand-foot-and-mouth disease	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Influenza	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Varicella	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0005 events3 affected20 at risk EG0010 events0 affected10 at risk
Staphylococcal infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected10 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG00013 events9 affected20 at risk EG0015 events4 affected10 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG00015 events10 affected20 at risk EG0014 events3 affected10 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected20 at risk EG0013 events3 affected10 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events2 affected20 at risk EG0010 events0 affected10 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected10 at risk
Pyrexia	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG00016 events9 affected20 at risk EG0019 events4 affected10 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG00019 events11 affected20 at risk EG0016 events4 affected10 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events2 affected20 at risk EG0011 events1 affected10 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0004 events2 affected20 at risk EG0010 events0 affected10 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected10 at risk
Dermatitis diaper	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0008 events7 affected20 at risk EG0016 events5 affected10 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG00010 events7 affected20 at risk EG0015 events3 affected10 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0003 events3 affected20 at risk EG0010 events0 affected10 at risk
Sapovirus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0003 events2 affected20 at risk EG0012 events1 affected10 at risk
Norovirus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0004 events4 affected20 at risk EG0011 events1 affected10 at risk
Adenovirus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Weight decreased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Enterococcus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected10 at risk
Weight gain poor	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0009 events7 affected20 at risk EG0013 events3 affected10 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected10 at risk
Headache	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0010 events0 affected10 at risk
Ocular hyperaemia	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0012 events2 affected10 at risk
Immune reconstitution inflammatory syndrome	Immune system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected20 at risk EG0012 events2 affected10 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0002 events2 affected20 at risk EG0011 events1 affected10 at risk
Adenovirus infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Bronchiolitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Epstein-Barr virus infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Gastroenteritis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Impetigo	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Laryngitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Parainfluenzae virus infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Tinea capitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Tinea infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Conjunctivitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected10 at risk
Haemophilus infection	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Herpes zoster	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Oral candidiasis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Dental caries	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Gastritis	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Oral mucosal erythema	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Tongue discolouration	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Proctitis	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Bronchial disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Blood blister	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Exfoliative rash	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Acinetobacter test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Influenza A virus test positive	Investigations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Morganella test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Aspiration bone marrow abnormal	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Blood creatinine increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
C-reactive protein increased	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Chest x-ray abnormal	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Computerised tomogram thorax abnormal	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Cytomegalovirus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Epstein-Barr virus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0003 events1 affected20 at risk EG0010 events0 affected10 at risk
Human metapneumovirus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Human rhinovirus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Respirovirus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Staphylococcus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Streptococcus test positive	Investigations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Abnormal loss of weight	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Feeding intolerance	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Developmental delay	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Infusion site erythema	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Catheter site erythema	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Chest pain	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Hypothermia	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Malaise	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Mucosal inflammation	General disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Hypermetropia	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Amblyopia	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Astigmatism	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Strabismus	Eye disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Gross motor delay	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Hypotonia	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Speech disorder developmental	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected20 at risk EG0010 events0 affected10 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Combined immunodeficiency	Congenital, familial and genetic disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Preauricular cyst	Congenital, familial and genetic disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Deafness	Ear and labyrinth disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Motion sickness	Ear and labyrinth disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Deafness neurosensory	Ear and labyrinth disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Thermal burn	Injury, poisoning and procedural complications	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Bradycardia	Cardiac disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Insomnia	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Attention deficit/hyperactivity disorder	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Testicular swelling	Reproductive system and breast disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0011 events1 affected10 at risk
Hypothyroidism	Endocrine disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Haemangioma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Azotaemia	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Hypertension	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk
Pallor	Vascular disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected20 at risk EG0010 events0 affected10 at risk

ID	Term
C531816	Severe combined immunodeficiency due to adenosine deaminase deficiency
D016511	Severe Combined Immunodeficiency

ID	Term
D000081207	Primary Immunodeficiency Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases
D049914	DNA Repair-Deficiency Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

ID	Term
D002072	Butylene Glycols
D006018	Glycols
D000438	Alcohols
D009930	Organic Chemicals
D008698	Mesylates
D000476	Alkanesulfonates
D017738	Alkanesulfonic Acids
D000473	Alkanes
D006839	Hydrocarbons, Acyclic
D006838	Hydrocarbons
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	OTL-101* On-Study and CUP Subjects	The safety population consists of all OTL-101*-treated subjects (on-study and CUP).	0	20	11	20	20	20
EG001	OTL-101* On-Study Subjects	The safety population for analysis consists of the on-study OTL-101*-treated subjects.	0	10	7	10	10	10