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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Wiskott-Aldrich Syndrome
• Intervention / Treatment: Genetic: OTL-103

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Healthcare of Atlanta, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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	Engraftment of of OTL-103 is measured by hematological reconstitution of an absolute neutrophil count > 500 cell/ul	6 months
The number of subjects presenting with malignancies or abnormal clonal proliferation		2 years
Evaluation of the overall survival		36 months

Collaborators and Investigators

• Sponsor: Fondazione Telethon
• Collaborators: Ospedale San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: February 8, 2019
• First Submitted That Met QC Criteria: February 11, 2019
• First Posted (Actual): February 12, 2019

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Disease; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Leukopenia; Leukocyte Disorders; Primary Immunodeficiency Diseases; Lymphopenia; Syndrome; Wiskott-Aldrich Syndrome
• Other Study ID Numbers: OTL-103-4; 2018-003842-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No