Efficacy &Safety of cryopreserved LV Gene Therapy in ADA-SCID patients
Research type
Research Study
Full title
EFFICACY AND SAFETY OF A 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 ADENOSINE DEAMINASE DEFICIENCY
IRAS ID
226667
Contact name
Claire Booth
Contact email
Sponsor organisation
Great Ormond Street Hospital for Children NHS Trust
Eudract number
2017-001275-23
Duration of Study in the UK
2 years, 10 months, 5 days
Research summary
Adenosine Deaminase (ADA) is an enzyme, needed by the body to develop lymphocytes of the immune system. Children who are born with mutations in ADA gene have severe combined immunodeficiency (SCID). Without treatment, children with ADA-SCID generally die in the first year of life from severe infections because they do not have an immune system that can fight against infection. ADA deficient individuals can be cured by a bone marrow transplant, but the best results are obtained when there is a fully matched donor family available (15-20% of cases). In the absence of a matched family donor, transplants from unrelated or mismatched donors have a much worse outcome. A form of enzyme replacement therapy (ERT) using pegylated ADA (PEG-ADA) has been developed but is still under compassionate use in Europe. Children receive injections of PEG-ADA 1-2 time/week. These injections can allow the immune system to recover to a level that protects children from infections. However, these weekly injections are very expensive (£125k-250k annually) and this chronic, long-term treatment is limited by the variability of immune reconstitution & risk of persistent lymphopenia, antibodies and the development of autoimmunity, resulting in a long-term survival of 78% over 20 years. A new ex-vivo gammaretroviral vector based gene therapy medicinal product has just been authorised in Europe (May 2016) for the treatment of ADA-SCID patients (Strimvelis®). Whilst Strimvelis® represents a definitive treatment option with 100% survival to date, its relevance in ADA-SCID is limited by its availability in one single location in Europe (Milan) and the insufficient immune reconstitution in some patients. Meanwhile, despite the absence of leukaemia in ADA-SCID patients treated with gammaretroviral vectors to date, long-term safety monitoring is required in all patients treated with Strimvelis® to totally exclude risk of insertional oncogenesis.
In this trial, a cryopreserved formulation of ex-vivo lentiviral vector based gene therapy (OTL-101) will be assessed in ADA-SCID patients. The vector construct in ex-vivo lentiviral gene therapy incorporates safety features that make it less prone to insertional oncogenesis. Previous clinical trials using fresh formulations of this product show very good safety and efficacy outcomes including long-term immune reconstitution. Also, the cryopreserved formulation of this medicinal product will eventually make this therapy available to ADA SCID patients worldwide.REC name
London - West London & GTAC Research Ethics Committee
REC reference
17/LO/1067
Date of REC Opinion
21 Sep 2017
REC opinion
Further Information Favourable Opinion