Retroviral Insertion Site Methodology Study

NCT03311074 | Withdrawn Phase 4

• 1 other identifier: STRIM-002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (2)

• Mean abundance measurement

  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.

  Up to 5 years

• Coefficient of variation measurement

  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.

  Up to 5 years

Secondary Outcomes (2)

• Measurement of clone abundance of more than 5 percent

  Up to 5 years

• Shannon diversity index measurement

  Up to 5 years

Study Arms (1)

Strimvelis treatment receivers

EXPERIMENTAL

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.

Genetic: Strimvelis

Interventions

Strimvelis GENETIC

Strimvelis is a gene therapy that aims to restore ADA function in hematopoietic cell lineages and prevent the immunological manifestations. Strimvelis is a cluster of differentiation (CD) 34+ cell enriched dispersion of human bone marrow derived hematopoietic stem cells for infusion which have been transduced with a retroviral vector containing the human ADA gene.

Strimvelis treatment receivers

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Telethon: lead

MeSH Terms

Conditions

Immune System Diseases; Severe combined immunodeficiency due to adenosine deaminase deficiency; Severe Combined Immunodeficiency

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes

Study Officials

• Fondazione Telethon

  Fondazione Telethon

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There will be no separate treatment groups in the study.

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: October 16, 2017
• Study Start: June 25, 2020
• Primary Completion: July 9, 2020
• Study Completion: July 9, 2020
• Last Updated: January 29, 2024

Record last verified: 2023-11