Methodology Study of Retroviral Insertion Site Analysis in Strimvelis Gene Therapy

Methodology Study to Investigate the Utility of Retroviral Insertion Site Analysis in Samples From Subjects Treated With Strimvelis Gene Therapy.

This study is a post approval commitment to evaluate the accuracy and precision of retroviral insertion site (RIS) analysis and its utility for investigating and predicting the potential for insertional oncogenesis in subjects treated with Strimvelis.

Study Overview

• Status: Active, not recruiting
• Conditions: Severe Combined Immunodeficiency Due to ADA Deficiency
• Intervention / Treatment: Genetic: Strimvelis

Detailed Description

This non-interventional, retrospective, methodology study will use peripheral blood and bone marrow samples previously taken from subjects treated with Strimvelis. The study does not require subjects to undergo any further treatment, intervention or blood withdrawal.

The objective of this methodology study is to evaluate the accuracy and precision of shearing extension primer tag selection ligation-mediated polymerase chain reaction (S-EPTS/LM-PCR) for RIS analysis and its utility for investigating and predicting the potential for insertional oncogenesis in subjects previously treated with Strimvelis for severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency.

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will use biological samples previously taken from subjects treated with Strimvelis gRV-GT.

Description

Inclusion Criteria

Subjects must have previously received treatment with gRV-GT, either during clinical development (clinical trials and early access programs) or in the post-marketing setting as the approved product (Strimvelis) or under hospital exemption, and for whom at least one biological sample is available that meets the following eligibility criteria::

1. Peripheral blood, bone marrow, or DNA extracted from either source.
2. Taken at least 6 months after gRV-GT.
3. Stored at -20oC or below since the time of sampling.
4. Likely to provide at least 1.5 μg of DNA (following extraction by the central laboratory).

Exclusion Criteria N/A

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Subjects Previously Treated with Strimvelis (or GSK2696273) Gene Therapy; It is expected that this study will include approximately 70 eligible samples from approximately 15 subjects previously treated with gamma retroviral gene therapy (gRV-GT).

Genetic: Strimvelis; This non-interventional, retrospective, methodology study will use peripheral blood and bone marrow samples previously taken from subjects treated with gRV-GT. The study does not require subjects to undergo any further treatment, intervention or blood withdrawal. Eligible samples will be shipped to a central laboratory and will undergo DNA extraction prior to S-EPTS/LM-PCR analysis. Each analysis run will include a control DNA sample and up to four subject samples. Each sample will be analysed in triplicate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the precision of S-EPTS/LM-PCR methodology for RIS analysis using control insertion site DNA	Precision will be determined by the variability (%CV) of the abundance data.	Retrospective sample analysis.
To assess the accuracy of S-EPTS/LM-PCR methodology for RIS using control insertion site DNA	Accuracy will be determined based on the difference between the mean retrieved abundance and the expected abundance of control DNA.	Retrospective sample analysis.

Collaborators and Investigators

• Sponsor: Fondazione Telethon
• Investigators: Study Director: Fondazione Telethon, Fondazione Telethon

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2021
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: June 21, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: gene therapy; retroviral vector; ada-scid
• Additional Relevant MeSH Terms: Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Severe Combined Immunodeficiency
• Other Study ID Numbers: STRIM-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No