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Gene Therapy for Wiskott-Aldrich Syndrome (TIGET-WAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01515462
Recruitment Status : Active, not recruiting
First Posted : January 24, 2012
Last Update Posted : February 6, 2023
Ospedale San Raffaele
Information provided by (Responsible Party):
Orchard Therapeutics

Brief Summary:
This is phase I/II protocol to evaluate the safety and efficacy of WAS gene transfer into hematopoietic stem/progenitor cells for the treatment of Wiskott Aldrich Syndrome.

Condition or disease Intervention/treatment Phase
Wiskott-Aldrich Syndrome (WAS) Genetic: OTL-103 Phase 1 Phase 2

Detailed Description:
Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene which encodes the WAS protein (WASP), a cytoskeletal regulator which is expressed exclusively in hematopoietic cells.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This will be a single-arm study. All subjects will receive OTL-103 gene therapy and will be followed up for 15 years post gene therapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
Actual Study Start Date : April 20, 2010
Actual Primary Completion Date : October 3, 2018
Estimated Study Completion Date : September 11, 2030

Arm Intervention/treatment
Experimental: OTL-103 gene therapy
Eligible subjects will receive intravenous (IV) infusion of OTL-103 gene therapy. Subjects affected by WAS who don't have a suitable matched donor for allogenic hematopoietic stem cell transplantation will be included
Genetic: OTL-103
OTL-103 is an autologous CD34+ cells collected from bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding Wiskott-Aldrich syndrome (WAS) protein
Other Name: Previously GSK2696275

Primary Outcome Measures :
  1. Conditioning regimen-related safety [ Time Frame: Two months after gene therapy ]
    Absence of engraftment failure or prolonged aplasia (<500/ul ANC with no evidence of bone marrow recovery) and surveillance of non haematological regimen related toxicity (for clinical features NCI >2, for metabolic/laboratory NCI >3)

  2. Safety of lentivirus gene transfer into HSC [ Time Frame: 3 years ]
    Short-term safety and tolerability of lentiviral-transduced cell infusion-long-term safety of lentiviral-transduced cell infusion (absence of Replication Competent Lentivirus (RCL) and abnormal clonal proliferation).

  3. Sustained engraftment of genetically corrected haematopoietic stem cells in peripheral blood and/or in bone marrow [ Time Frame: 1 year ]
    ≥ 0.04 Vector copy number (VCN)/cell in bone marrow CD34+ or ≥0.1 VCN/cell in peripheral blood T lymphocytes

  4. Expression of vector-derived WASP [ Time Frame: 1 year ]
    Detection of vector-derived WASP expression by FACS analyses and/or Western Blot

  5. Improved T-cell functions [ Time Frame: 3 years ]
    Improvement in in vitro T cell proliferation and/or IL-2 secretion upon stimulation with anti-CD3i as compared to pre-gene therapy values.

  6. Antigen-specific responses to vaccination [ Time Frame: >1year ]
    Ability to mount a humoral response to nominal antigens including antibodies to T cell dependent antigens (Tetanus Toxoid) and unconjugated polysaccharide antigens (Peumococcus, Meningococcus), measured after vaccination (foreseen >1 year after gene therapy). Positive cellular response to Tetanus Toxoid after vaccination measured by in vitro proliferative response >1 year after gene therapy.

  7. Improved platelet count and MPV normalization [ Time Frame: 3 years ]
    Sustained increase in platelet count compared to baseline, analyzing the individual longitudinal profile

  8. Overall survival [ Time Frame: 3 years ]
    Number of patients alive all over the trial

Secondary Outcome Measures :
  1. Lack of immune response to transgene [ Time Frame: 3 years ]
    Immunoblot analysis

  2. Reduced frequency of severe infections [ Time Frame: 3 years ]
    Decrease in number of severe infections as evaluated in the second and third year after the treatment by clinical history, complete physical examinations, hematological and microbiological tests.

  3. Reduced bruising and bleeding episodes [ Time Frame: 3 years ]
    Reduction in bruising and/or bleeding manifestations when present, as assessed by clinical monitoring, compared to clinical history

  4. Reduced autoimmunity phenomena and eczema [ Time Frame: 3 years ]
    Reduction in laboratory markers (number and titer of antibody when available) and/or clinical manifestations of autoimmunity, as evaluated by organ-specific and systemic autoantibodies, imaging and clinical follow-up, compared to clinical history. Reduction in eczema as evaluated by clinical score

  5. Improved quality of life [ Time Frame: 3 year ]
    Improved quality of life, measured after the first year of treatment by reduced hospitalization, reduced requirement of drugs, school attendance, social activities.

  6. Multilineage engraftment of genetically corrected cells [ Time Frame: 3 years ]
    ≥0.04 VCN/cell on all the available peripheral blood and/or bone marrow cell subpopulations (BM subpopulations: GlyA+, CD15+, CD61+, CD3+, CD19+, CD56+; PB subpopulations: CD15+, CD19+, CD56+)

  7. Overall safety of the treatment [ Time Frame: 8 years ]
    Recording of AE, AR, SAE/SAR, UAR, SUSAR

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:

    • Severe WAS mutation
    • Absence of WASP expression
    • Severe clinical score (Zhu clinical score ≥ 3
  2. No HLA-identical sibling donor
  3. Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months

    • Patients of > 5 years of age who are not candidate to unrelated allogeneic transplant based on clinical conditions.
  4. Parental/guardian/patient signed informed consent.

Exclusion Criteria:

  1. Patients positive for HIV-infection.
  2. Patients affected by neoplasia.
  3. Patients with cytogenetic alterations typical of MDS/AML.
  4. Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study.
  5. Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months.
  6. Patients who underwent an allogeneic haematopoietic stem cell transplantation with evidence of residual cells of donor origin.

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 identifier (NCT number): NCT01515462

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Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Milan, Italy, 20132
Sponsors and Collaborators
Orchard Therapeutics
Ospedale San Raffaele
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Study Director: Orchard Clinical Trials Orchard Therapeutics

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Orchard Therapeutics Identifier: NCT01515462    
Other Study ID Numbers: 201228
2009-017346-32 ( EudraCT Number )
First Posted: January 24, 2012    Key Record Dates
Last Update Posted: February 6, 2023
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Orchard Therapeutics:
Lentiviral vector
Gene therapy
Wiskott-Aldrich Syndrome
Previously GSK2696275
Additional relevant MeSH terms:
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Wiskott-Aldrich Syndrome
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukocyte Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Primary Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Immune System Diseases