Don't get left behind! The modernized is coming. Check it out now.
Say goodbye to!
The new site is coming soon - go to the modernized
Working… Menu
Trial record 1 of 1 for:    NCT03837483
Previous Study | Return to List | Next Study

A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome

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: NCT03837483
Recruitment Status : Active, not recruiting
First Posted : February 12, 2019
Last Update Posted : March 28, 2023
Ospedale San Raffaele
Information provided by (Responsible Party):
Orchard Therapeutics

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
Wiskott-Aldrich Syndrome Genetic: OTL-103 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Open-label Clinical Trial of Hematopoietic Stem Cell Gene Therapy With Cryopreserved Autologous CD34+ Cells Transduced With Lentiviral Vector Encoding WAS cDNA in Subjects With Wiskott-Aldrich Syndrome (WAS)
Actual Study Start Date : January 21, 2019
Estimated Primary Completion Date : September 2025
Estimated Study Completion Date : September 2027

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

Primary Outcome Measures :
  1. Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy [ Time Frame: 18 months ]
  2. Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Evaluation of the overall survival [ Time Frame: 36 months ]
  2. Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells [ Time Frame: 2 years ]
  3. Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes [ Time Frame: 2 years ]
  4. Percentage of WAS protein expression increased from pre-treatment levels in platelets [ Time Frame: 2 years ]
  5. Number of participants with successful engraftment of OTL-103 [ Time Frame: 6 months ]
    Engraftment of of OTL-103 is measured by hematological reconstitution of an absolute neutrophil count > 500 cell/ul

  6. The number of subjects presenting with malignancies or abnormal clonal proliferation [ Time Frame: 2 years ]

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.

Layout table for eligibility information
Ages Eligible for Study:   up to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age: up to 65 years
  • Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:

    • Severe Wiskott-Aldrich Syndrome (WAS) gene mutation, defined by literature data (genotype/phenotype studies).;
    • Absent WASP expression, assessed by flow cytometry;
    • Severe clinical score (Zhu clinical score ≥ 3);
  • No human leukocyte antigen (HLA)-identical related donor available for hematopoietic stem cells transplant (HSCT).

Exclusion Criteria:

  • 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.
  • Malignant neoplasia (except local skin cancer) or a documented history of hereditary cancer syndrome.
  • Myelodysplasia, cytogenetic alterations characteristic of myelodysplastic syndrome and acute myeloid leukaemia , or other serious haematological disorders
  • Documented human immunodeficiency virus (HIV) infection
  • Prior allogeneic hematopoietic stem cell transplantation, with evidence of residual cells of donor origin
  • Symptomatic herpes zoster, not responsive to specific treatment
  • Evidence of acute tuberculosis
  • Acute or chronic stable Hepatitis B
  • Presence of positive Hepatitis C RNA test result at screening
  • Patients not eligible for mobilization protocols in order to obtain CD34+ cells
  • Previous Gene Therapy

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): NCT03837483

Layout table for location information
United States, Georgia
Children's Healthcare of Atlanta, Inc
Atlanta, Georgia, United States, 30329
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Milan, Italy, 20132
Sponsors and Collaborators
Orchard Therapeutics
Ospedale San Raffaele
Layout table for investigator information
Study Director: Orchard Clinical Trials Orchard Therapeutics (Europe) Limited
Layout table for additonal information
Responsible Party: Orchard Therapeutics Identifier: NCT03837483    
Other Study ID Numbers: OTL-103-4
2018-003842-18 ( EudraCT Number )
First Posted: February 12, 2019    Key Record Dates
Last Update Posted: March 28, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
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