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

Phase 3

Active, not recruiting

• Conditions: Wiskott-Aldrich Syndrome
• Interventions: Genetic: OTL-103

• Registration Number: NCT03837483
• Lead Sponsor: Fondazione Telethon

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 available

Study Timeline

• Study Start: 2019-01-21
• Study First Submitted: 2019-02-08
• Study First Submitted QC: 2019-02-11
• Study First Posted: 2019-02-12
• Status Verified: 2023-03
• Last Update Submitted: 2024-01-29
• Last Update Posted: 2024-01-31
• Primary Completion: 2025-09
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gene Therapy	OTL-103	OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene

Primary Outcome Measures

Name	Time	Method
Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy	12 months
Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy	18 months

Secondary Outcome Measures

Name	Time	Method
The number of subjects presenting with malignancies or abnormal clonal proliferation	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
Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells	2 years
Evaluation of the overall survival	36 months

Trial Locations

Locations (2)

Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET); 🇮🇹 Milan, Italy

Children's Healthcare of Atlanta, Inc; 🇺🇸 Atlanta, Georgia, United States