Clinical trial NCT03837483: A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Wiskott-Aldrich Syndrome
Lead sponsor: Fondazione Telethon
Sponsor class: OTHER
Collaborators: name: Ospedale San Raffaele
First posted: 2019-02-12
Enrollment: 10
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy
timeFrame: 18 months
measure: Annualized rate of moderate and severe bleeding episodes up to 1 year after gene therapy compared with 1 year before gene therapy
timeFrame: 12 months
Secondary outcomes:
measure: Evaluation of the overall survival
timeFrame: 36 months
measure: Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells
timeFrame: 2 years
measure: Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes
timeFrame: 2 years
measure: Percentage of WAS protein expression increased from pre-treatment levels in platelets
timeFrame: 2 years
measure: Number of participants with successful engraftment of OTL-103
timeFrame: 6 months
measure: The number of subjects presenting with malignancies or abnormal clonal proliferation
timeFrame: 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta, Inc
state: Georgia
city: Milan
country: Italy
facility: Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Study officials:
References: