Retroviral Insertion Site Methodology Study
Primary Purpose
Immune System Diseases
Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Strimvelis
Sponsored by
About this trial
This is an interventional treatment trial for Immune System Diseases focused on measuring Sonication Linker Medicated Polymerase Chain Reaction, Previously GSK2696273, Gene therapy, Adenosine deaminase deficiency, Retroviral insertion site, Severe combined immunodeficiency, Strimvelis
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Strimvelis treatment receivers
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Measurement of clone abundance of more than 5 percent
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.
Shannon diversity index measurement
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03311074
Brief Title
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
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Replaced with new observational study design
Study Start Date
June 25, 2020 (Anticipated)
Primary Completion Date
July 30, 2024 (Anticipated)
Study Completion Date
July 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Orchard Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune System Diseases
Keywords
Sonication Linker Medicated Polymerase Chain Reaction, Previously GSK2696273, Gene therapy, Adenosine deaminase deficiency, Retroviral insertion site, Severe combined immunodeficiency, Strimvelis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
There will be no separate treatment groups in the study.
Masking
None (Open Label)
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.
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Strimvelis treatment receivers
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
Strimvelis
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mean abundance measurement
Description
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.
Time Frame
Up to 5 years
Title
Coefficient of variation measurement
Description
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.
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Measurement of clone abundance of more than 5 percent
Description
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.
Time Frame
Up to 5 years
Title
Shannon diversity index measurement
Description
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.
Time Frame
Up to 5 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Orchard Clinical Trials
Organizational Affiliation
Orchard Therapeutics
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Retroviral Insertion Site Methodology Study
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