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

January 26, 2024 updated by: Fondazione Telethon
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel
        • Investigational Site
  • Italy
    • Lombardia
      • Milano, Lombardia, Italy, 20132
        • Ospedale San Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 15 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: baseline to 3 years post gene therapy
From post-treatment to up to 3 years
baseline to 3 years post gene therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Before Treatment and 3-months post-treatment up to 3 years
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).
baseline up to 3 years post gene therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Telethon

Investigators

  • Study Director: Fondazione Telethon, Fondazione Telethon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 2, 2002

Primary Completion (Actual)

July 10, 2011

Study Completion (Actual)

June 19, 2019

Study Registration Dates

First Submitted

January 10, 2008

First Submitted That Met QC Criteria

January 21, 2008

First Posted (Estimated)

January 22, 2008

Study Record Updates

Last Update Posted (Actual)

January 29, 2024

Last Update Submitted That Met QC Criteria

January 26, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STRIM-004
  • 15386-PRE21 (Other Identifier: IRCCS San Raffaele)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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