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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Last refreshed on: 12 December 2020
Main ID:  NCT03765632
Date of registration: 08/08/2018
Prospective Registration: Yes
Primary sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Public title: Efficacy and Safety of the Cryopreserved Formulation of OTL-101 in Subjects With ADA-SCID
Scientific title: Efficacy and Safety of a Cryopreserved Formulation of Autologous CD34+ Haematopoietic Stem Cells Transduced ex Vivo With Elongation Factor 1a Short Form (EFS) Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency (SCID) Due to Adenosine Deaminase Deficiency
Date of first enrolment: January 3, 2018
Target sample size: 10
Recruitment status: Recruiting
Study type:  Interventional
Study design:  Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 1/Phase 2
Countries of recruitment
United Kingdom
Name:     Claire Booth, Dr
Telephone: +44 (0) 207 905 2198
Name:     Claire Booth, Dr
Telephone: +44 (0)207 905 2198
Name:     Claire Booth, Dr
Affiliation:  Great Ormond Street Hospital NHS Foundation Trust
Key inclusion & exclusion criteria

Inclusion Criteria:

1. Provision of written informed consent prior to any study related procedures. In this
study consent must be provided by the parents/legal guardians and, where applicable
according to local laws, a signed assent from the child

2. Subjects =30 days and <18 years of age,

3. With a diagnosis of ADA-SCID based on:

1. . Evidence of ADA deficiency, defined as: i. Decreased ADA enzymatic activity in
erythrocytes, leukocytes, skin fibroblasts, or in cultured foetal cells to levels
consistent with ADA-SCID as determined by the reference laboratory, or ii.
Identified mutations in ADA alleles consistent with a severe reduction in ADA

2. . Evidence of ADA-SCID based on either: i. Family history of a first order
relative with ADA deficiency and clinical and laboratory evidence of severe
immunologic deficiency, or ii. Evidence of severe immunologic deficiency in
subjects prior to the institution of immune restorative therapy, based on

Lymphopenia (absolute lymphocyte count <400 cells/mL) OR absence or low number of
T-cells (absolute CD3+ count < 300 cells/mL), or

Severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (either
<10% of lower limit of normal controls for the diagnostic laboratory, or <10% of the
response of the normal control of the day, or stimulation index <10), or

Identification of SCID by neonatal screening revealing low T cell Receptor Excision
Circle (TREC) levels.

4. Ineligible for or with no available matched family donor for allogeneic Bone Marrow
(BM) transplantation, defined as the absence of a medically eligible HLA-identical
sibling or family donor, with normal immune function, who could serve as an allogeneic
bone marrow donor.

5. Females of child-bearing age will be required to provide a negative pregnancy test 30
days prior to Visit 2.

6. Subjects and their parents/legal guardians must be willing and able to comply with
study restrictions and to remain at the clinic for the required duration during the
study period and willing to return to the clinic for the follow up evaluation as
specified in the protocol.

Exclusion Criteria:

1. Ineligible for autologous hematopoietic stem cell (HSC) procedure.

2. Other conditions which in the opinion of the Principal Investigator and/or
Co-Investigators, contraindicate the harvest of bone marrow, the administration of
Busulfan and the infusion of transduced cells, or which indicate an inability of the
subject or subject's parent/legal guardian to comply with the protocol.

3. Haematologic abnormality, defined as:

Anaemia (Hb <8.0 g/dl). Evidence of bi/trilineage cytopaenia (haemoglobin <8 g/dl,
neutrophils <0.5 x 109/L, platelets 50 x 109/L). Thrombocytopaenia (platelet count
<50,000/mm3). Prothrombin time or partial thromboplastin time (PTT) >2 x upper limit
of normal (ULN) (subjects with a correctable deficiency controlled on medication will
not be excluded).

- Cytogenetic abnormalities of Peripheral Blood (PB), BM or amniotic fluid (if
available). If cytogenetic testing has not been performed on cells from
amniocentesis, assessment should be by karyotype, Comparative genomic
hybridization (CGH), and or whole exome sequencing (WES).

- Prior allogeneic HSC transplant (HSCT) with cytoreductive conditioning.

4. Pulmonary abnormality, defined as:

- Resting O2 saturation by pulse oximetry <90% on room air.

- Chest X-ray indicating active or progressive pulmonary disease. Note: Chest X-ray
indicating residual signs of treated pneumonitis is acceptable for eligibility.

5. Cardiac abnormality, defined as:

- Abnormal ECG indicating cardiac pathology.

- Uncorrected congenital cardiac malformation with clinical symptoms.

- Active cardiac disease, including clinical evidence of congestive heart failure,
cyanosis, hypotension.

- Poor cardiac function as evidenced by left ventricular ejection fraction <40% on

6. Neurologic abnormality, defined as:

- Significant neurologic abnormality revealed by examination.

- Uncontrolled seizure disorder.

7. Known history of significant renal abnormality.

8. Known history of significant hepatic or gastrointestinal abnormality.

9. Oncologic disease, defined as:

- Evidence of active malignant disease other than Dermatofibrosarcoma Protuberans(
DFSP) 2.

- Evidence of DFSP expected to require anti-neoplastic therapy within the 5 years
following the infusion of genetically corrected cells (if anti-neoplastic therapy
has been completed, a subject with a history of DFSP can be included).

- Evidence of DFSP expected to be life-limiting within the 5 years following the
infusion of genetically corrected cells.

10. Known sensitivity to Busulfan.

11. Confirmation of an infectious disease by deoxyribonucleic acid (DNA) polymerase chain
reactions (PCR) positive at time of screening assessment according to local
protocols/procedures (including HIV-1 and hepatitis B).

12. The subject is pregnant or has a major congenital anomaly.

13. Is likely to require treatment during the study with drugs that are not permitted by
the study protocol.

14. The subject has previously received another form of gene therapy.

Age minimum: N/A
Age maximum: 17 Years
Gender: All
Health Condition(s) or Problem(s) studied
Severe Combined Immunodeficiency Due to ADA Deficiency
Drug: Busulfan
Drug: Peg-Ada
Genetic: Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101)
Primary Outcome(s)
Event free survival at 12 months post OTL-101 infusion [Time Frame: 12 Months]
Overall survival at 12 months post OTL-101 infusion [Time Frame: 12 Months]
Secondary Outcome(s)
Event free survival at 24 months post OTL-101 infusion [Time Frame: 24 Months]
Overall survival at 24 months post OTL-101 infusion [Time Frame: 24 months]
Safety evaluation including immune reconstitution [Time Frame: 12 and 24 months]
Safety evaluation including infection rates [Time Frame: 12 and 24 months]
Safety evaluation including performance outcomes [Time Frame: 12 and 24 months]
Secondary ID(s)
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Orchard Therapeutics
Ethics review
Results available:
Date Posted:
Date Completed:
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