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

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ClinicalTrials.gov Identifier: NCT00598481
Recruitment Status : Completed
First Posted : January 22, 2008
Results First Posted : July 31, 2020
Last Update Posted : July 31, 2020
Information provided by (Responsible Party):
Orchard Therapeutics

Brief Summary:
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 human leukocyte-antigen (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 cluster of differentiation (CD)34+ 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 or disease Intervention/treatment Phase
Immunologic Deficiency Syndromes Genetic: Gene Therapy Drug: Busulfan Drug: PEG-ADA Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID
Actual Study Start Date : October 2, 2002
Actual Primary Completion Date : July 10, 2011
Actual Study Completion Date : June 19, 2019

Arm Intervention/treatment
Experimental: Gene Therapy
Infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with busulfan
Genetic: Gene Therapy
Infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with busulfan
Other Names:
  • Gene transduced CD34+ cells
  • GSK2696273
  • Strimvelis

Drug: Busulfan
Busulfan is used for non-myeloablative conditioning

polyethylene glycol (PEG)-ADA is discontinued prior to gene therapy

Primary Outcome Measures :
  1. Survival [ Time Frame: baseline to 3 years post gene therapy ]
    From post-treatment to up to 3 years

Secondary Outcome Measures :
  1. Rate of Severe Infections [ Time Frame: Before Treatment and 3-months post-treatment up to 3 years ]
    Severe infections were defined as those that required hospitalization or those that prolonged hospitalization. The rate of infection was estimated as number of severe infections over person-years of observation (free from severe infections) before and after treatment administration. The first 3 months after gene therapy were not considered in the post-gene therapy analysis, because all subjects were hospitalized during this period.

  2. CD3+ Cell Counts [ Time Frame: baseline up to 3 years post gene therapy ]
    T-lymphocyte counts (CD3+): mean T-lymphocyte at Baseline and 3 years post gene therapy. Samples were taken from peripheral venous whole blood and tested by cytofluorometry; values are means (10^6/L).

Information from the National Library of Medicine

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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 available
  • 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

Exclusion Criteria:

  • HIV infection
  • history or current malignancy
  • Patients who received a previous gene therapy treatment in the 12 months prior to receiving Strimvelis
  • any other conditions dangerous for the patients according to the investigator

Information from the National Library of Medicine

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): NCT00598481

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Investigational Site
Jerusalem, Israel
Investigational Site
Milano, Lombardia, Italy, 20132
Sponsors and Collaborators
Orchard Therapeutics
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Study Director: Orchard Clinical Trials Orchard Therapeutics
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Orchard Therapeutics
ClinicalTrials.gov Identifier: NCT00598481    
Other Study ID Numbers: STRIM-004
15386-PRE21 ( Other Identifier: IRCCS San Raffaele )
First Posted: January 22, 2008    Key Record Dates
Results First Posted: July 31, 2020
Last Update Posted: July 31, 2020
Last Verified: July 2020
Keywords provided by Orchard Therapeutics:
gene therapy
Adenosine deaminase
retroviral vector
Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Immune System Diseases
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists