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

September 23, 2025 updated by: Fondazione Telethon

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

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: 18 months
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
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
Time Frame: 2 years
2 years
Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes
Time Frame: 2 years
2 years
Percentage of WAS protein expression increased from pre-treatment levels in platelets
Time Frame: 2 years
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
6 months
The number of subjects presenting with malignancies or abnormal clonal proliferation
Time Frame: 2 years
2 years
Evaluation of the overall survival
Time Frame: 36 months
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Telethon

Collaborators

Ospedale San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 21, 2019

Primary Completion (Actual)

March 18, 2024

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)

September 29, 2025

Last Update Submitted That Met QC Criteria

September 23, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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