Methodology Study of Retroviral Insertion Site Analysis in Strimvelis Gene Therapy

Severe Combined Immunodeficiency Due to ADA Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04959890
• Other study ID #: STRIM-005
• Status: Active, not recruiting
• Start date: April 23, 2021
• Est. completion date: March 31, 2024

Study information

• Verified date: January 2024
• Source: Fondazione Telethon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Severe Combined Immunodeficiency
• Severe Combined Immunodeficiency Due to ADA Deficiency

Intervention

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.

Locations

Country	Name	City	State
Italy	Ospedale San Raffaele	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Telethon

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.