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

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ClinicalTrials.gov Identifier: NCT03837483
Recruitment Status : Active, not recruiting
First Posted : February 12, 2019
Last Update Posted : December 8, 2020
Sponsor:
Collaborator:
Ospedale San Raffaele
Information provided by (Responsible Party):
Orchard Therapeutics

Tracking Information
First Submitted Date  ICMJE February 8, 2019
First Posted Date  ICMJE February 12, 2019
Last Update Posted Date December 8, 2020
Actual Study Start Date  ICMJE January 21, 2019
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
  • Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy [ Time Frame: 18 months ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2019)
Number of participants with successful engraftment of OTL-103 [ Time Frame: 6 months ]
Engraftment of of OTL-103 is measured by the following parameters:
  • hematological reconstitution of an absolute neutrophil count > 500 cell/ul
  • a vector copy number of > 0.1 in peripheral blood-derived CD3+ cells
  • WAS protein expression in lymphocytes greater than pre-treatment values
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
  • Evaluation of the overall survival [ Time Frame: 24 months ]
  • Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells [ Time Frame: 2 years ]
  • Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes [ Time Frame: 2 years ]
  • Percentage of WAS protein expression increased from pre-treatment levels in platelets [ Time Frame: 2 years ]
  • 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
  • The number of subjects presenting with malignancies or abnormal clonal proliferation [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2019)
  • Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells [ Time Frame: 2 years ]
  • WAS protein expression increased from pre-treatment levels in lymphocytes and platelets [ Time Frame: 2 years ]
  • Evaluate the immunological function after treatment with OTL-103 [ Time Frame: 2 years ]
    Evaluate immunological function by measuring T-cell function (proliferation to stimulaiton) and response to vaccinations
  • Evaluate the safety by the absence of malignancies or abnormal clonal proliferation [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Wiskott-Aldrich Syndrome
Intervention  ICMJE Genetic: OTL-103
Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA
Study Arms  ICMJE Experimental: Gene Therapy
OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene
Intervention: Genetic: OTL-103
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 11, 2019)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Previous Gene Therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03837483
Other Study ID Numbers  ICMJE OTL-103-4
2018-003842-18 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Orchard Therapeutics
Study Sponsor  ICMJE Orchard Therapeutics
Collaborators  ICMJE Ospedale San Raffaele
Investigators  ICMJE
Study Director: Orchard Clinical Trials Orchard Therapeutics (Europe) Limited
PRS Account Orchard Therapeutics
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP