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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 : Active, not recruiting
First Posted : January 22, 2008
Last Update Posted : January 8, 2019
Sponsor:
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 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 or disease Intervention/treatment Phase
Immunologic Deficiency Syndromes Genetic: Gene Therapy 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.

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


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
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
Estimated Study Completion Date : June 30, 2019


Arm Intervention/treatment
Experimental: Gene Therapy
Infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with Busulphan
Genetic: Gene Therapy
Infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with Busulphan
Other Name: Gene transduced CD34+ cells




Primary Outcome Measures :
  1. Survival [ Time Frame: minimum of 1 year ]

Secondary Outcome Measures :
  1. Change in the rate of severe infection [ Time Frame: During follow up ]
  2. T-lymphocyte counts [ Time Frame: one year ]
  3. Modification of the systemic metabolic defect [ Time Frame: one year ]
  4. Presence of genetically modified cells in the Bone Marrow and Peripheral Blood [ Time Frame: one year ]


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

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 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


Locations
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Israel
Investigational Site
Jerusalem, Israel
Italy
Investigational Site
Milano, Lombardia, Italy, 20132
Sponsors and Collaborators
Orchard Therapeutics
Investigators
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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     History of Changes
Other Study ID Numbers: STRIM-004
15386-PRE21 ( Other Identifier: IRCCS San Raffaele )
First Posted: January 22, 2008    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: January 2019

Keywords provided by Orchard Therapeutics:
SCID
gene therapy
Adenosine deaminase
retroviral vector

Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Immune System Diseases