- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03311074
Retroviral Insertion Site Methodology Study
January 26, 2024 updated by: Fondazione Telethon
Methodology Study to Investigate the Utility of Retroviral Insertion Site Analysis in Samples From Subjects Treated With Strimvelis™ Gene Therapy
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 Overview
Study Type
Interventional
Phase
- Phase 4
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 5 years
|
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.
|
Up to 5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measurement of clone abundance of more than 5 percent
Time Frame: Up to 5 years
|
Abundance of clones in subject's samples will be measured by SLiM-PCR, where abundance estimates will be derived from the number of individual sheared DNA fragments and the number of DNA barcodes in the linker sequences.
|
Up to 5 years
|
Shannon diversity index measurement
Time Frame: Up to 5 years
|
The Shannon diversity index is an index that is commonly used to characterize species diversity in a community.
The diversity of the clones in subject's samples will be determined using Shannon diversity.
Shannon diversity index will be summarized using mean and coefficient of variation.
|
Up to 5 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Fondazione Telethon, Fondazione Telethon
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 25, 2020
Primary Completion (Actual)
July 9, 2020
Study Completion (Actual)
July 9, 2020
Study Registration Dates
First Submitted
October 11, 2017
First Submitted That Met QC Criteria
October 11, 2017
First Posted (Actual)
October 16, 2017
Study Record Updates
Last Update Posted (Actual)
January 29, 2024
Last Update Submitted That Met QC Criteria
January 26, 2024
Last Verified
November 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STRIM-002
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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