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

Study Overview
=================
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.

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)

Conditions
-----------------
Wiskott-Aldrich Syndrome

Intervention / Treatment
-----------------
* Genetic: OTL-103


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gene Therapy<br>OTL-103, Autologous CD34+ hematopoietic stem cells transduced ex vivo with a lentiviral vector encoding the human WAS gene | Genetic: OTL-103<br>* Autologous hematopoietic stem cells collected from mobilized peripheral blood transduced ex vivo with a lentiviral vector encoding the WAS cDNA<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |
| --- | --- | --- |
| 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 | 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 |