A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome
Study Details
Study Description
Brief Summary
This is an open-label, single arm study to evaluate the cryopreserved formulation of OTL-103 Gene Therapy. OTL-103 consists of autologous CD34+ hematopoietic stem cells in which the gene encoding for the Wiskott-Aldrich Syndrome is introduced by means of a third generation lentiviral vector.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Gene Therapy OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene |
Genetic: OTL-103
Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA
|
Outcome Measures
Primary Outcome Measures
- Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy [18 months]
- Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy [12 months]
Secondary Outcome Measures
- Evaluation of the overall survival [24 months]
- Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells [2 years]
- Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes [2 years]
- Percentage of WAS protein expression increased from pre-treatment levels in platelets [2 years]
- Number of participants with successful engraftment of OTL-103 [6 months]
Engraftment of of OTL-103 is measured by hematological reconstitution of an absolute neutrophil count > 500 cell/ul
- The number of subjects presenting with malignancies or abnormal clonal proliferation [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age: up to 65 years
-
Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:
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Severe Wiskott-Aldrich Syndrome (WAS) gene mutation, defined by literature data (genotype/phenotype studies).;
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Absent WASP expression, assessed by flow cytometry;
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Severe clinical score (Zhu clinical score ≥ 3);
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No human leukocyte antigen (HLA)-identical related donor available for hematopoietic stem cells transplant (HSCT).
Exclusion Criteria:
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End-organ dysfunction, severe active infection not responsive to treatment or other severe disease or clinical condition which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
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Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome.
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Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukaemia , or other serious haematological disorders
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Documented human immunodeficiency virus (HIV) infection
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Prior allogeneic hematopoietic stem cell transplantation, with evidence of residual cells of donor origin
-
Previous Gene Therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Healthcare of Atlanta, Inc | Atlanta | Georgia | United States | 30329 |
| 2 | Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET) | Milan | Italy | 20132 |
Sponsors and Collaborators
- Orchard Therapeutics
- Ospedale San Raffaele
Investigators
- Study Director: Orchard Clinical Trials, Orchard Therapeutics (Europe) Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OTL-103-4
- 2018-003842-18