Autologous Cryopreserved CD34+ Hematopoietic Cells Transduced With Elongation Factor 1α Short Form Adenosine Deaminase (EFS-ADA) Lentivirus for Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency (ADA-SCID)
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|ClinicalTrials.gov Identifier: NCT02999984|
Recruitment Status : Completed
First Posted : December 21, 2016
Last Update Posted : February 25, 2020
|Condition or disease||Intervention/treatment||Phase|
|Severe Combined Immunodeficiency Due to ADA Deficiency||Genetic: Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101)||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 subjects 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 clinical study is also to assess the success of treatment at the subject level ("responder analysis") 6 months post OTL-101 infusion, using predictive criteria for overall survival and event free survival and to compare data obtained from clinical studies using the fresh formulation of OTL-101.
Eligible subjects will be hospitalized 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 subjects will be readmitted for conditioning prior to infusion of OTL-101.
For subjects who have successfully received the OTL-101 product, PEG-ADA ERT will be discontinued at Day+30 (-3/+15) after the transplant. After their discharge from hospital, the subjects 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 subjects will have completed the study and may enter a long term registry.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy and Safety of Cryopreserved Formulation of Autologous CD34+ Hematopoietic Stem Cells Transduced Ex Vivo With EFS Lentiviral Vector Encoding for Human ADA Gene in Subjects With Severe Combined Immunodeficiency Due to ADA Deficiency|
|Actual Study Start Date :||December 16, 2016|
|Actual Primary Completion Date :||October 11, 2018|
|Actual Study Completion Date :||September 26, 2019|
Experimental: Gene Therapy
Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells
Genetic: Infusion of autologous cryopreserved EFS-ADA LV CD34+ cells (OTL-101)
Infusion of OTL-101 after reduced intensity busulfan conditioning. PEG-ADA ERT is discontinued at Day +30 (-3/+15 days) after successful engraftment
Other Name: OTL-101
- The number of subjects with treatment success post OTL-101 infusion [ Time Frame: 6 Months ]
Defined as meeting or exceeding the threshold for all three of the following parameters:
- Erythrocyte ADA enzyme activity above baseline/pre-treatment level (>0 Units),
- Evidence of immune reconstitution as measured by absolute number of CD3 cells ≥200/mm3),
- Detectable gene-marked granulocytes as measured by differential polymerase chain reaction (dPCR)/ quantitative PCR (qPCR) (≥1/10,000 cells).
- Overall survival [ Time Frame: 12 Months ]Overall survival is defined as the proportion of subjects alive.
- Event free survival [ Time Frame: 12 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 allogenic Hematopoietic Stem Cell Transplant (HSCT), or death.
- Overall survival [ Time Frame: 24 months ]Overall survival is defined as the proportion of subjects alive.
- Event free survival [ 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 allogenic HSCT, or death.
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): NCT02999984
|United States, California|
|University of California, Los Angeles|
|Los Angeles, California, United States, 90095|
|Study Director:||Donald B. Kohn, MD||University of California, Los Angeles|