Methodology Study to Investigate the Utility of Retroviral Insertion Site Analysis in Samples From Subjects Treated With Strimvelis™ Gene Therapy
Trial Snapshot
- Phase
- Phase 4
- Status
- Withdrawn
- Sponsor
- Fondazione Telethon
- Primary Endpoint
- Mean abundance measurement
Study Overview
Brief Summary
Adenosine deaminase (ADA) is an enzyme involved in the development and functioning of the immune system. Deficiency of ADA results in severe combined immunodeficiency (SCID), a fatal inherited immune disorder. Strimvelis is a gene therapy that aims to insert ADA function into blood cells and halt or reverse the conditions caused by decreased ADA enzyme levels, such as impaired immune function. It is important to consider long term follow-up of patients who have received Strimvelis, including evaluation of the risk of insertion near certain genes that may lead to unexpected activation of those genes (oncogenesis). The objective of this study is to evaluate the use of a new technique to identify where Strimvelis has become inserted in the genetic sequence, and potential implications for patient care. This new technique is known as sonication linker mediated polymerase chain reaction (SLiM-PCR) for retroviral insertion site (RIS) analysis. The study will recruit at least 15 pediatric or adult patients with ADA-SCID who have been treated with Strimvelis, either in previous clinical trials or as a registered product. Recruitment for the study may remain open for up to 2 years even if 15 subjects are recruited sooner. Study participation will last for up to 5 years. A total of 5 blood samples will be collected from each subject at approximately annual intervals.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Masking Description
No masking will be performed in the study and all subjects who have received Strimvelis, either in previous clinical trials or as a registered product, will be included in the analysis.
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female, pediatric or adult, subjects with ADA-SCID, who have been previously treated with Strimvelis.
- •Capable of giving signed informed consent or signed informed consent provided by the subject's parent or legal guardian.
Exclusion Criteria
- •Presence of concomitant condition(s) that in the Investigator's opinion makes participation in the study unsuitable or may prevent compliance with the protocol requirements.
- •Unlikely to comply with the requirements of the protocol (i.e. attendance for blood sampling on an approximately annual basis).
- •Transportation of viable samples to the European Union (EU) central laboratory from the subject's home country is not possible.
Arms & Interventions
Strimvelis treatment receivers
Approximately 15 subjects with ADA-SCID who were previously received Strimvelis will be included in the analysis and a total of 5 blood samples will be collected from each subject at approximately annual interval.
Intervention: Strimvelis (Genetic)
Outcomes
Primary Outcomes
Mean abundance measurement
Time Frame: Up to 5 years
The accuracy and precision of SLiM-PCR methodology will be assessed using whole blood samples, taken from subjects treated with Strimvelis, spiked with control insertion site deoxyribonucleic acid (DNA). The mean abundance will be calculated between subjects at every time point, within subjects over time points and between the same sample within a time point within a subject.
Coefficient of variation measurement
Time Frame: Up to 5 years
The accuracy and precision of SLiM-PCR methodology will be assessed using whole blood samples, taken from subjects treated with Strimvelis, spiked with control insertion site DNA. The coefficient of variation will be calculated between subjects at every time point, within subjects over time points and between the same sample within a time point within a subject.
Secondary Outcomes
- Shannon diversity index measurement(Up to 5 years)
- Measurement of clone abundance of more than 5 percent(Up to 5 years)