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ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID (Gene-ADA)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: January 10, 2008
Last updated: April 21, 2016
Last verified: April 2016
This is a phase I/II protocol to evaluate the safety and efficacy of ADA gene transfer into hematopoietic stem/progenitor cells for the treatment of adenosine deaminase (ADA)-deficiency. This condition is an autosomal recessive form of Severe Combined Immunodeficiency (SCID) characterized by impaired immune responses, recurrent infections, failure to thrive and systemic toxicity due to accumulation of purine metabolites. Transplants from an HLA-identical sibling donor is the treatment of choice, but available for a minority of patients. The use of alternative bone marrow donors or enzyme replacement therapy is associated with important drawbacks. The drug product studied in this protocol consists of autologous CD34+ hematopoietic stem/progenitor cells engineered ex vivo with a retroviral vector encoding the therapeutic gene ADA. The engineered CD34+ cells are infused following a nonmyeloablative conditioning with busulfan to make space in the bone marrow. The study objectives are: a) to evaluate the safety and the clinical efficacy of gene therapy, in the absence of enzyme replacement therapy; b) to evaluate the biological activity (engraftment, ADA expression) of ADA transduced CD34+ cells and their hematopoietic progeny. c) to evaluate the immunological reconstitution and purine metabolism after gene therapy.

Condition Intervention Phase
Immunologic Deficiency Syndromes
Genetic: Gene transduced CD34+ cells
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • survival [ Time Frame: minimum of 1 year ]

Secondary Outcome Measures:
  • Change in the rate of severe infection [ Time Frame: During follow up ]
  • T-lymphocyte counts [ Time Frame: one year ]
  • Modification of the systemic metabolic defect [ Time Frame: one year ]
  • presence of genetically modified cells in the BM and PB [ Time Frame: one year ]

Enrollment: 18
Study Start Date: October 2002
Estimated Study Completion Date: June 2019
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CD34+ cells
infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with Busulphan
Genetic: Gene transduced CD34+ cells
infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with Busulphan
Other Name: Gene therapy

Detailed Description:

The safety of the study will be evaluated by description of all adverse events and adverse drug reactions.

The study is aimed at reaching the minimum sample size of ten patients.

Long term follow up all patients enrolled into the study will have a long term follow period from 4 to 8 years after gene therapy


Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • ADA-SCID with no HLA-identical sibling donor
  • pediatric age and at least one of the following criteria:
  • inadequate immune response after PEG-ADA for > 6 months
  • patients who discontinued PEG-ADA due to intolerance, allergy or auto-immunity
  • patients for whom enzyme replacement therapy is not a life long therapeutic option Long term follow-up
  • Patients who have received treatment with the Medicinal Product, either as part of the main clinical study, or previous pilot studies or compassionate use program

Exclusion Criteria:

  • HIV infection
  • history or current malignancy
  • Patients who received a previous gene therapy treatment in the 12 months prior to receiving GSK2696273
  • any other conditions dangerous for the patients according to the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00598481

GSK Investigational Site
Jerusalem, Israel
GSK Investigational Site
Milan, Italy, 20132
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):

Responsible Party: GlaxoSmithKline Identifier: NCT00598481     History of Changes
Other Study ID Numbers: 115611
15386-PRE21 ( Other Identifier: IRCCS San Raffaele )
Study First Received: January 10, 2008
Last Updated: April 21, 2016

Keywords provided by GlaxoSmithKline:
gene therapy
Adenosine deaminase
retroviral vector

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases processed this record on May 25, 2017