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

Wiskott-Aldrich Syndrome Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03837483
• Other study ID #: OTL-103-4
• Secondary ID: 2018-003842-18
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 21, 2019
• Est. completion date: September 2027

Study information

• Verified date: March 2023
• Source: Fondazione Telethon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: September 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Syndrome
• Wiskott-Aldrich Syndrome

Intervention

Genetic:
• OTL-103
Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA

Locations

Country	Name	City	State
Italy	Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)	Milan
United States	Children's Healthcare of Atlanta, Inc	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Fondazione Telethon	Ospedale San Raffaele

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy		18 months
Primary	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	Evaluation of the overall survival		36 months
Secondary	Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells		2 years
Secondary	Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes		2 years
Secondary	Percentage of WAS protein expression increased from pre-treatment levels in platelets		2 years
Secondary	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
Secondary	The number of subjects presenting with malignancies or abnormal clonal proliferation		2 years