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)
2 other identifiers
interventional
10
2 countries
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Jan 2019
Longer than P75 for phase_3
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 21, 2019
CompletedFirst Submitted
Initial submission to the registry
February 8, 2019
CompletedFirst Posted
Study publicly available on registry
February 12, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 18, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2027
ExpectedSeptember 29, 2025
September 1, 2025
5.2 years
February 8, 2019
September 23, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (6)
Evaluation of the overall survival
36 months
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
6 months
- +1 more secondary outcomes
Study Arms (1)
Gene Therapy
EXPERIMENTALOTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene
Interventions
Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fondazione Telethonlead
- Ospedale San Raffaelecollaborator
Study Sites (2)
Children's Healthcare of Atlanta, Inc
Atlanta, Georgia, 30329, United States
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Milan, 20132, Italy
Related Publications (1)
Quaranta P, Basso-Ricci L, Jofra Hernandez R, Pacini G, Naldini MM, Barcella M, Seffin L, Pais G, Spinozzi G, Benedicenti F, Pietrasanta C, Cheong JG, Ronchi A, Pugni L, Dionisio F, Monti I, Giannelli S, Darin S, Fraschetta F, Barera G, Ferrua F, Calbi V, Ometti M, Di Micco R, Mosca F, Josefowicz SZ, Montini E, Calabria A, Bernardo ME, Cicalese MP, Gentner B, Merelli I, Aiuti A, Scala S. Circulating hematopoietic stem/progenitor cell subsets contribute to human hematopoietic homeostasis. Blood. 2024 May 9;143(19):1937-1952. doi: 10.1182/blood.2023022666.
PMID: 38446574DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 8, 2019
First Posted
February 12, 2019
Study Start
January 21, 2019
Primary Completion
March 18, 2024
Study Completion (Estimated)
September 1, 2027
Last Updated
September 29, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share