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

• ClinicalTrials.gov Identifier: NCT03837483
• Recruitment Status: Active, not recruiting
• First Posted: February 12, 2019
• Last Update Posted: March 28, 2023
• Sponsor: Orchard Therapeutics
• Collaborator: Ospedale San Raffaele
• Information provided by (Responsible Party): Orchard Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Wiskott-Aldrich Syndrome	Genetic: OTL-103	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: January 21, 2019
• Estimated Primary Completion Date: September 2025
• Estimated Study Completion Date: September 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Annualized rate of severe infections from 6 to 18 months after gene therapy compared with 1 year before gene therapy [ Time Frame: 18 months ]
2. 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 ]

Secondary Outcome Measures :

1. Evaluation of the overall survival [ Time Frame: 36 months ]
2. Number of patients with Vector copy number (VCN)/cell > 0.1 measured in peripheral blood-derived CD3+ cells [ Time Frame: 2 years ]
3. Percentage of WAS protein expression increased from pre-treatment levels in lymphocytes [ Time Frame: 2 years ]
4. Percentage of WAS protein expression increased from pre-treatment levels in platelets [ Time Frame: 2 years ]
5. 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. The number of subjects presenting with malignancies or abnormal clonal proliferation [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: up to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Georgia

Children's Healthcare of Atlanta, Inc

Atlanta, Georgia, United States, 30329

Italy

Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)

Milan, Italy, 20132

Sponsors and Collaborators

Orchard Therapeutics

Ospedale San Raffaele

Investigators

• Study Director: Orchard Clinical Trials; Orchard Therapeutics (Europe) Limited

More Information

• Responsible Party: Orchard Therapeutics
• ClinicalTrials.gov Identifier: NCT03837483
• Other Study ID Numbers: OTL-103-4; 2018-003842-18 ( EudraCT Number )
• First Posted: February 12, 2019
• Last Update Posted: March 28, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Wiskott-Aldrich Syndrome; Syndrome; Disease; Pathologic Processes; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphopenia; Leukopenia; Leukocyte Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immune System Diseases