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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.
Register: EUCTR
Last refreshed on: 30 June 2019
Main ID:  EUCTR2017-001275-23-GB
Date of registration: 03/07/2017
Prospective Registration: Yes
Primary sponsor: Great Ormond Street Hospital for Children NHS Trust
Public title: A clinical trial to study the effects of genetically modified patients' CD34+ cells
Scientific title: Efficacy and safety of a cryopreserved formulation of autologous CD34+ haematopoietic stem cells transduced ex vivo with EFS lentiviral vector encoding for human ADA gene in subjects with Severe Combined Immunodeficiency (SCID) due to Adenosine Deaminase Deficiency
Date of first enrolment: 21/09/2017
Target sample size: 10
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001275-23
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: no
Randomised: no
Open: yes
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
United Kingdom
Contacts
Name: Cecile Duret   
Address:  30 Guilford Street WC1N 1E London United Kingdom
Telephone: +44(0)2079052292
Email: c.duret@ucl.ac.uk
Affiliation:  UCL Institute of Child Health
Name: Cecile Duret   
Address:  30 Guilford Street WC1N 1E London United Kingdom
Telephone: +44(0)2079052292
Email: c.duret@ucl.ac.uk
Affiliation:  UCL Institute of Child Health
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 evidence of ADA deficiency or evidence of ADA-SCID,
4. Ineligible for or with no available matched family donor for allogeneic 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Ineligible for autologous haematopoietic 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,
4. Pulmonary abnormality,
5. Cardiac abnormality,
6. Neurologic abnormality,
7. Renal abnormality,
8. Hepatic/gastrointestinal abnormality,
9. Oncologic disease,
10. Known sensitivity to Busulfan,
11. Confirmation of an infectious disease by deoxyribonucleic acid (DNA) PCR positive at time of assessment for the following: HIV-1, Hepatitis B, Parvovirus B19,
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:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). Children with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. If not treated in a way that restores immune function, children with SCID usually live only a year or two.
MedDRA version: 20.1 Level: LLT Classification code 10066372 Term: ADA deficiency System Organ Class: 100000004850
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Intervention(s)

Product Name: cryopreserved EFS-ADA LV transduced patient CD34+ cells
Product Code: OTL-101
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: There is no recommended INN
Other descriptive name: Autologous CD34+ HSCs transduced ex vivo with EFS lentiviral vector encoding for the human ADA gene
Concentration unit: Other
Concentration type: range
Concentration number: 2000000-20000000

Primary Outcome(s)
Main Objective: - Efficacy: Evaluate the overall survival and event free survival 12 months post OTL-101 administration.
- Safety: The safety and tolerability of OTL-101.
Primary end point(s): Evaluate the overall survival and event free survival 12 months post OTL-101 administration.
Overall survival is defined as the proportion of subjects alive. Event free survival is defined as the proportion of subjects alive with no “event”; an “event” being the resumption of PEG-ADA ERT or the need for a rescue allogenic HSCT, or death.
Secondary Objective: - Evaluate the overall survival and event free survival 24 months post GTMP administration.
- Immunoglobulin Replacement therapies prior to and after gene therapy.
- Safety and tolerability.
- Performance outcomes and quality of life will be measured by the Karnofsky/Lansky scale and questions relevant to general well-being, school attendance and ability to practice sports, respectively.
- Evaluation of the frequency of severe infections or opportunistic infectious episodes; defines as infections or severe infections requiring hospitalisation or prolonged hospitalisation and/or documented infections by opportunistic pathogens (i.e. interstitial pneumonia, intractable diarrhoea).
- Response to tetanus vaccination.
- Immune reconstitution: T and B cell reconstitution.
Timepoint(s) of evaluation of this end point: 12 months post OTL-101 administration
Secondary Outcome(s)
Secondary end point(s): - Evaluate the overall survival and event free survival 24 months post OTL-101 administration
- Immunoglobulin Replacement therapies prior to and after gene therapy.
- Safety and tolerability.
- Performance outcomes and quality of life will be measured by the Karnofsky/Lansky scale and questions relevant to general well-being, school attendance and ability to practice sports.
- Evaluation of the frequency of severe infections or opportunistic infectious episodes, defines as infections or severe infections requiring hospitalisation or prolonging hospitalisation and/or documented infections by opportunistic pathogens (i.e. interstitial pneumonia, intractable diarrhoea).
- Response to tetanus vaccination.
- Immune reconstitution: T and B cell reconstitution.
Timepoint(s) of evaluation of this end point: 24 months post OTL-101 administration
Secondary ID(s)
OTL-101-5(17IC04)
Source(s) of Monetary Support
Orchard Therapeutics
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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