Clinical trial NCT03311074: Retroviral Insertion Site Methodology Study
Official title: Methodology Study to Investigate the Utility of Retroviral Insertion Site Analysis in Samples From Subjects Treated With Strimvelis™ Gene Therapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Immune System Diseases
Keywords: Sonication Linker Medicated Polymerase Chain Reaction
Previously GSK2696273
Gene therapy
Adenosine deaminase deficiency
Retroviral insertion site
Severe combined immunodeficiency
Strimvelis
Lead sponsor: Fondazione Telethon
Sponsor class: OTHER
First posted: 2017-10-16
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: There will be no separate treatment groups in the study.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean abundance measurement
timeFrame: Up to 5 years
measure: Coefficient of variation measurement
timeFrame: Up to 5 years
Secondary outcomes:
measure: Measurement of clone abundance of more than 5 percent
timeFrame: Up to 5 years
measure: Shannon diversity index measurement
timeFrame: Up to 5 years
Other outcomes:
Locations:
Study officials:
affiliation: Fondazione Telethon
name: Fondazione Telethon
role: STUDY_DIRECTOR
References: