Gene Therapy for Patients With ADA Adenosine Deaminase (ADA) Deficiency
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|ClinicalTrials.gov Identifier: NCT03765632|
Recruitment Status : Recruiting
First Posted : December 5, 2018
Last Update Posted : December 6, 2018
Adenosine Deaminase (ADA) is an enzyme, needed by body to develop lymphocytes of the immune system. Children who are born in mutations with mutations in ADA gene have severe combined immunodeficiency (SCID). Children with ADA-deficient SCID generally die in the first year of life from severe infections because they do not have immune system that can fight against infections. ADA deficient individuals can be cured by bone marrow transplant, but the best results are obtained when there is fully matched family donor is available. In the absence of a matched related donor, transplants from unrelated or mismatched donors have a much worse outcome. There is a form of enzyme therapy (PEG-ADA) for ADA-deficient SCID, in which children receive injections of purified ADA enzyme 1-2 times each week. These injections can allow the immune system to recover to a level that protects children from infections.
However, these injections have to be given weekly and are very expensive (£ 125,000 - 200,000 annually) and the recovery of the immune system is not sustained over time.
Gene therapy for ADA-deficient SCID could be performed by introducing a normal copy of the human ADA gene into the blood forming stem cells of the patient's bone marrow by using a new type of gene delivery system (in this trial called a lentiviral vector). The gene corrected cells are then transplanted back into the patient after small dose of chemotherapy. These gene corrected stem cells can survive into the body and make lymphocytes. In this trial, the investigator will determine whether gene therapy for ADA-deficient SCID using a cryopreserved lentiviral vector is safe, feasible and effective
|Condition or disease||Intervention/treatment||Phase|
|Ada-Scid||Drug: Lentiviral transduced CD34+ cells||Phase 1 Phase 2|
This is a prospective, non-randomized, single-cohort, longitudinal, single-center, clinical study designed to assess the efficacy and safety of a cryopreserved formulation of OTL-101 (autologous CD34+ hematopoietic stem cells transduced ex vivo with EFS LV encoding for the human ADA gene) administered to ADA-SCID patients between the ages of 30 days and 17 years, who are not eligible for an HLA-matched sibling/family donor and meeting the inclusion/exclusion criteria.
The aim of this study is to assess the success of treatment for overall survival and event free survival.
Eligible patients will be hospitalised to undergo the harvesting of autologous CD34+ cells. To enable the release of the cell product for infusion, the product must meet various quality control criteria for safety, identity, viability, purity and potency. If OTL-101 meets the acceptance criteria and is released, the patients will be readmitted for conditioning prior to infusion of OTL-101.
For patients who have successfully received the OTL-101 product, PEG-ADA ERT will be discontinued at Day+30 (+/-3) after the transplant. After the patients discharge from hospital, the patients will be seen at regular intervals to review their history, perform examinations and draw blood samples at Months 1, 3, 6, 9, 12, 18, and 24. Any medically-indicated interventions will be determined at these visits. After Month 24 visit, the patients will have completed the study and may enter a long term registry.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Cryopreserved Lentivirus Gene Therapy for Adenosine Deaminase (ADA) Deficiency|
|Actual Study Start Date :||January 2, 2018|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||March 2021|
Experimental: Lentiviral transduced CD34+ cells
OTL-101, a cryopreserved formulation of autologous CD34+ haematopoietic stem cells transduced ex vivo with Elongation Factor 1α Short form (EFS) lentiviral vector (LV) encoding for the human adenosine deaminase deficiency (ADA) gene
Drug: Lentiviral transduced CD34+ cells
Biological: Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells
Other Name: OTL-101
- Overall survival at 12 months post OTL-101 infusion [ Time Frame: 12 Months ]Overall survival is defined as the proportion of subjects alive. as the proportion of subjects alive with no "event", an "event" being the resumption of PEG-ADA ERT or the need for a rescue SCT, or death free survival in ADA-SCID patients treated with a cryopreserved formulation of OTL-101.
- Event free survival at 12 months post OTL-101 infusion defined as Death, returning to PEG-ADA Enzyme Replacement Therapy (ERT) or Need of rescue Stem Cell Transplant (SCT) [ Time Frame: 12 Months ]Event-free survival is defined as the time-to event from the OTL-101 infusion if an event occurred, or to the date of the last evaluation without an event if no event occurred.
- Overall survival at 24 months post OTL-101 infusion [ Time Frame: 24 months ]
Overall survival is defined as the proportion of subject's alive post OTL-101 infusion.
Safety evaluation includes frequency of severe infections or opportunistic infectious episodes (defined as infections or severe infections requiring hospitalisation or prolonging hospitalisation and/or documented infections by opportunistic pathogens (i.e. interstitial pneumonia, intractable diarrhoea), performance outcomes and immune response.
- 3. Event free survival at 24 months and safety evaluation as assessed by number of patients with Grade 3 through Grade 5 adverse events that are related to the intervention, graded according to NCI CTCAE Version 3.0 [ Time Frame: 24 Months ]
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 SCT, or death. Safety evaluations are event free survival.
Safety evaluation and will be assessed throughout the study by evaluating adverse events including infections, clinical laboratory test results, vital signs measurements, physical examination results, and concomitant medication usage.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03765632
|Contact: Claire Booth, Dr||+44 (0)207 905 email@example.com|
|Great Ormond Street Hospital for Children NHS Trust||Recruiting|
|London, United Kingdom, WC1N 3JH|
|Contact: Claire Booth, Dr +44(0)207 905 2198 C.Booth@ucl.ac.uk|
|Contact: Kajal Soni, Miss 0207 762 6056 firstname.lastname@example.org|
|Principal Investigator: Claire Booth, Dr|
|Principal Investigator:||Claire Booth, Dr||UCL Great Ormond Street Institute of Child Health|