Gene Transfer for ADA-SCID Using an Improved Lentiviral Vector (TYF-ADA)

• ClinicalTrials.gov Identifier: NCT03645460
• Recruitment Status: Unknown
• First Posted: August 24, 2018
• Last Update Posted: September 20, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: July 17, 2018
• First Posted Date: August 24, 2018
• Last Update Posted Date: September 20, 2019
• Actual Study Start Date: October 30, 2018
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 22, 2018)

Overall survival up to a year [ Time Frame: 15 years ]

Patient will be monitored for overall health condition, including immune cell assessments, blood biochemistry and metabolitic activities, metabolic detoxification, gene-modified cell percentage and vector copy number (VCN) in the blood, and continued follow-up for 15 years.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 22, 2018)

• 1. Success of immune reconstitution [ Time Frame: 12 month ]
  Immunological and metabolic values including all leukocyte counts (ALC), T, B and NK cell counts (CD3, CD4, CD8, CD19, CD56), T cell TREC levels, T cell repertoire diversity, PHA proliferation rate, immunoglobulins and dATP levels will be measured.
• 2. Change of infection status [ Time Frame: 12 month ]
  Immune recovery associated with reduction of infection episodes and frequencies, including viral, fungal and bacterial infections will be documented.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gene Transfer for ADA-SCID Using an Improved Lentiviral Vector (TYF-ADA)
• Official Title: Gene Transfer for Adenosine Deaminase-severe Combined Immunodeficiency (ADA-SCID) Using an Improved Self-inactivating Lentiviral Vector (TYF-ADA)
• Brief Summary: Gene transfer for ADA-SCID using an improved lentiviral vector (TYF-ADA)

Detailed Description

This clinical trial will evaluate a safety and efficiency improved lentiviral vector system for delivering a therapeutic gene to patients with severe combined immunodeficiency (SCID) due to a defective adenosine deaminase (ADA) gene. This gene encodes for the adenosine deaminase enzyme, which is essential for the proper growth and function of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are vulnerable to frequent and severe infections.

ADA-SCID patients are normally rescued by a bone marrow transplant (BMT) from a matched healthy donor. However, matched donors are difficult to find and donor BMT is associated with high risk. This trial aims to treat ADA-SCID using a safety and efficiency improved self-inactivating lentiviral vector carrying a functional ADA gene to correct the genetic defect. By collecting an individual's stem cells and modifying them with a lentivirus, the gene-corrected cells can be returned to the patient to help produce normal healthy immune cells.The primary objectives are to evaluate the safety of the improved self-inactivating lentiviral vector TYF-ADA, the ex vivo gene transfer clinical protocol and the efficacy of immune reconstitution in patients overcoming frequent infections present at the time of treatment. We will assess the lentiviral gene integration sites and the long-term effect of this gene transfer procedure.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Adenosine DeAminase Severe Combined ImmunoDeficiency (ADA-SCID)

Intervention

Genetic: TYF-ADA gene-modified autologous stem cells

Infusion of TYF-ADA-modified autologous stem cells at 1~10x10^6 gene-modified cells per kg body weight; or more infusions depending on the circumstances

Study Arms

Experimental: TYF-ADA-modified autologous stem cells

Autologous hematopoietic and/or mesenchymal stem cells transduced with lentiviral vector carrying the ADA gene

Intervention: Genetic: TYF-ADA gene-modified autologous stem cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 22, 2018): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: December 31, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of classical ADA-SCID based on:

  • A proven defective adenosine deaminase (ADA) gene as defined by direct sequencing of patient DNA.
  • T-cell immune deficiency defined as one or more of the following: CD3+ autologous T cells < 300/ul, or less than 50% of normal value for in vitro mitogen stimulation, or absent proliferation in vitro to antigens.
• With severe infections, including but not limited to: pneumonitis; protracted diarrhea requiring total parenteral nutrition; infection with herpes viruses or adenovirus or fungus; disseminated BCG infection.
• No cytogenetic abnormalities (medullary karyotype) and no detection of main rearrangements associated with acute leukemia of children.
• No prior allogeneic stem cell transplantation.
• Life expectancy ≥ 2 months.
• Negative for HIV infection.
• Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

• None

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03645460
• Other Study ID Numbers: GIMI-IRB-18003
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lung-Ji Chang, Ph.D; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019