Trial Outcomes & Findings for Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA) Deficiency (NCT NCT01380990)

NCT ID: NCT01380990

Last Updated: 2021-09-16

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

36 participants

Primary outcome timeframe

12 months

Results posted on

2021-09-16

Participant Flow

Participant milestones

Participant milestones
Measure	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	Historical Control Group Historical data from patients with Severe Combined Immunodeficiency Due to ADA Deficiency (ADA-SCID) who were treated with Hematopoietic Stem Cell Transplantation (HSCT) Haematopoietic Stem Cell Transplantation (HSCT): Historical data from a database of ADA-SCID patients treated with allogeneic HSCT from Great Ormond Street Hospital (GOSH) will be collected as comparator group.
Overall Study STARTED	20	16
Overall Study COMPLETED	19	15
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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	Historical Control Group Historical data from patients with Severe Combined Immunodeficiency Due to ADA Deficiency (ADA-SCID) who were treated with Hematopoietic Stem Cell Transplantation (HSCT) Haematopoietic Stem Cell Transplantation (HSCT): Historical data from a database of ADA-SCID patients treated with allogeneic HSCT from Great Ormond Street Hospital (GOSH) will be collected as comparator group.
Overall Study Treatment Failure	1	0
Overall Study Death	0	1

Baseline Characteristics

Lentiviral (LV) Gene Therapy for Adenosine Deaminase (ADA) Deficiency

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gene Therapy n=20 Participants 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).	Historical Control Group n=16 Participants 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)	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	20 Participants n=5 Participants	16 Participants n=7 Participants	36 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex/Gender, Customized Sex, n · Female	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Sex/Gender, Customized Sex, n · Male	12 Participants n=5 Participants	0 Participants n=7 Participants	12 Participants n=5 Participants
Sex/Gender, Customized Sex, n · Not Reported	0 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity, n · Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity, n · White European	10 Participants n=5 Participants	0 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity, n · Other	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity, n · Unknown	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity, n · Not reported	0 Participants n=5 Participants	16 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United Kingdom	20 participants n=5 Participants	16 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

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

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=10 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=20 Participants 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).	HSCT Controls Without MRD n=5 Participants 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.	HSCT Controls With MRD n=11 Participants Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016	All HSCT Controls n=16 Participants 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)
Overall Survival (OS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)	100 percentage of participants Interval 69.15 to 100.0	100 percentage of participants Interval 83.16 to 100.0	100 percentage of participants Interval 47.82 to 100.0	100 percentage of participants Interval 71.51 to 100.0	100 percentage of participants Interval 79.41 to 100.0

PRIMARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=10 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=20 Participants 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).	HSCT Controls Without MRD n=5 Participants 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.	HSCT Controls With MRD n=11 Participants Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016	All HSCT Controls n=16 Participants 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)
Event-free Survival (EvFS) of Subjects Treated With Investigational Medicinal Product (IMP) (1 Year)	100 percentage of participants Interval 69.15 to 100.0	100 percentage of participants Interval 83.16 to 100.0	100 percentage of participants Interval 47.82 to 100.0	100 percentage of participants Interval 71.51 to 100.0	100 percentage of participants Interval 79.41 to 100.0

PRIMARY outcome

Timeframe: 36 months

Population: 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

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

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=9 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=18 Participants 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).	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.	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	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)
Vector Copy Number (VCN) in Granulocytes Fraction (Neutrophils)	0.240 copies/cell Interval 0.15 to 0.79	0.280 copies/cell Interval 0.03 to 1.6	—	—	—

PRIMARY outcome

Timeframe: 36 months

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

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=9 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=18 Participants 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).	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.	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	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)
VCN in Peripheral Blood Mononuclear Cells (PBMCs)	0.600 copies/cell Interval 0.2 to 1.67	0.625 copies/cell Interval 0.2 to 1.67	—	—	—

PRIMARY outcome

Timeframe: 36 months

Engraftment of transduced cells was assessed using vector gene marking

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=8 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=17 Participants 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).	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.	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	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)
VCN in CD3+ T Cells	1.065 copies/cell Interval 0.84 to 1.59	1.160 copies/cell Interval 0.3 to 4.61	—	—	—

PRIMARY outcome

Timeframe: 36 months

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

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=9 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=17 Participants 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).	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.	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	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)
VCN in CD19+ B Cells	0.880 copies/cell Interval 0.68 to 1.77	1.190 copies/cell Interval 0.68 to 3.75	—	—	—

PRIMARY outcome

Timeframe: 12 months

Population: 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

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

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=8 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=17 Participants 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).	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.	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	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)
Change From Baseline in CD3+ T Cell Counts (1 Year)	3.58 10e9 cells/L Interval 1.64 to 7.83	3.18 10e9 cells/L Interval 1.98 to 5.1	—	—	—

PRIMARY outcome

Timeframe: 36 months

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

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=7 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=16 Participants 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).	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.	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	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)
Change From Baseline in CD3+ T Cell Counts (3 Years)	1.060 10e9 cells/L Interval 0.59 to 1.47	1.090 10e9 cells/L Interval -0.49 to 1.47	—	—	—

PRIMARY outcome

Timeframe: 36 months

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.

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=8 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=16 Participants 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).	HSCT Controls Without MRD n=3 Participants 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.	HSCT Controls With MRD n=7 Participants Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016	All HSCT Controls n=10 Participants 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)
ADA Activity in Erythrocytes	638.0 nmol/h/mg Interval 220.0 to 3038.0	490.5 nmol/h/mg Interval 27.0 to 3038.0	86.5 nmol/h/mg Interval 39.0 to 115.0	1.0 nmol/h/mg Interval 0.0 to 27.0	23.0 nmol/h/mg Interval 0.0 to 115.0

PRIMARY outcome

Timeframe: 36 months

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.

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=6 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=12 Participants 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).	HSCT Controls Without MRD n=1 Participants 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.	HSCT Controls With MRD n=5 Participants Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016	All HSCT Controls n=6 Participants 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)
Reduction in Deoxyadenosine Triphosphate (dATP) in Erythrocytes	50.0 umol/L Interval 50.0 to 50.0	50.0 umol/L Interval 50.0 to 50.0	0.0 umol/L Interval 0.0 to 0.0	114.0 umol/L Interval 23.0 to 192.0	90.0 umol/L Interval 0.0 to 192.0

PRIMARY outcome

Timeframe: 36 months

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.

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=10 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=20 Participants 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).	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.	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	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)
Frequency of Vector Integration Into Known Protooncogenes (3 Years)	0 % of integration in known protooncogenes	0 % of integration in known protooncogenes	—	—	—

SECONDARY outcome

Timeframe: 36 months

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

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=10 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=20 Participants 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).	HSCT Controls Without MRD n=5 Participants 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.	HSCT Controls With MRD n=11 Participants Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016	All HSCT Controls n=16 Participants 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)
OS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)	100 percentage of participants Interval 66.37 to 100.0	100 percentage of participants Interval 82.35 to 100.0	100 percentage of participants Interval 47.82 to 100.0	88.89 percentage of participants Interval 51.75 to 99.72	92.86 percentage of participants Interval 66.13 to 99.82

SECONDARY outcome

Timeframe: 36 months

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=10 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=20 Participants 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).	HSCT Controls Without MRD n=5 Participants 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.	HSCT Controls With MRD n=11 Participants Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016	All HSCT Controls n=16 Participants 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)
EvFS of Subjects Treated With IMP With Those of Patients Treated With Allogeneic HSCT (3 Years)	90.00 percentage of participants Interval 55.5 to 99.75	95.00 percentage of participants Interval 75.13 to 99.87	80.00 percentage of participants Interval 28.36 to 99.49	60.00 percentage of participants Interval 26.24 to 87.84	66.67 percentage of participants Interval 38.38 to 88.18

SECONDARY outcome

Timeframe: 36 months

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.

Outcome measures

Outcome measures
Measure	OTL-101* On-Study Subjects n=10 Participants The primary efficacy population for analysis consists of the on-study OTL-101\*-treated subjects.	OTL-101* On-Study and CUP Subjects n=20 Participants 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).	HSCT Controls Without MRD n=5 Participants 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.	HSCT Controls With MRD n=11 Participants Secondary efficacy population for comparison comprise ADA-SCID patients with an MRD treated with HSCT at GOSH from 2000 to 2016	All HSCT Controls n=16 Participants 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)
Infection Rate	0.14 Infection rate per person per year	0.14 Infection rate per person per year	0.13 Infection rate per person per year	0.17 Infection rate per person per year	0.16 Infection rate per person per year

Adverse Events

OTL-101* On-Study and CUP Subjects

Serious events: 11 serious events

Other events: 20 other events

Deaths: 0 deaths

OTL-101* On-Study Subjects

Serious events: 7 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr Claire Booth

UCL Institute of Child Health

Phone: +44207 905 2198

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OTL-101* On-Study and CUP Subjects n=20 participants at risk The safety population consists of all OTL-101\*-treated subjects (on-study and CUP).	OTL-101* On-Study Subjects n=10 participants at risk The safety population for analysis consists of the on-study OTL-101\*-treated subjects.
General disorders Pyrexia	30.0% 6/20 • Number of events 8 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	50.0% 5/10 • Number of events 7 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Device related infection	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	30.0% 3/10 • Number of events 4 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Device related sepsis	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	10.0% 1/10 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Gastroenteritis norovirus	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	10.0% 1/10 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Influenza	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	10.0% 1/10 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Oral candidiasis	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	0.00% 0/10 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Pneumonia	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	0.00% 0/10 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Transmission of an infectious agent via product	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	0.00% 0/10 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Infections and infestations Urinary tract infection bacterial	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	0.00% 0/10 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Immune system disorders Immune reconstitution inflammatory syndrome	10.0% 2/20 • Number of events 3 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	20.0% 2/10 • Number of events 3 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Gastrointestinal disorders Diarrhoea	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	10.0% 1/10 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Gastrointestinal disorders Vomiting	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	10.0% 1/10 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	10.0% 1/10 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Respiratory, thoracic and mediastinal disorders Cough	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	0.00% 0/10 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Metabolism and nutrition disorders Weight gain poor	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	10.0% 1/10 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.
Blood and lymphatic system disorders Bone marrow failure	5.0% 1/20 • Number of events 1 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.	0.00% 0/10 • Adverse events were reported from the time of participant consent, approximately 1-month pre-treatment, up until 3-years post-treatment with OTL-101* Adverse events were reported for subjects treated with OTL-101\*. Adverse event reporting is not applicable for the historical control arms (without MRD, with MRD, and all control patients) as this data was not collected due to the historical nature of the population.