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Retroviral Insertion Site Methodology Study

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ClinicalTrials.gov Identifier: NCT03311074
Recruitment Status : Not yet recruiting
First Posted : October 16, 2017
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
Orchard Therapeutics

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.

Condition or disease Intervention/treatment Phase
Immune System Diseases Biological: Strimvelis Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Intervention 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.
Primary Purpose: Treatment
Official Title: Methodology Study to Investigate the Utility of Retroviral Insertion Site Analysis in Samples From Subjects Treated With Strimvelis™ Gene Therapy
Estimated Study Start Date : September 30, 2019
Estimated Primary Completion Date : July 30, 2024
Estimated Study Completion Date : July 30, 2024


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.
Biological: Strimvelis
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 Measures :
  1. 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.

  2. 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 Outcome Measures :
  1. 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.

  2. 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.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03311074


Contacts
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Contact: Orchard Clinical Trials +44 (0) 203 384 6700 medinfo@orchard-tx.com

Sponsors and Collaborators
Orchard Therapeutics
Investigators
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Study Director: Orchard Clinical Trials Orchard Therapeutics

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Responsible Party: Orchard Therapeutics
ClinicalTrials.gov Identifier: NCT03311074     History of Changes
Other Study ID Numbers: STRIM-002
First Posted: October 16, 2017    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Orchard Therapeutics:
Sonication Linker Medicated Polymerase Chain Reaction
Previously GSK2696273
Gene therapy
Adenosine deaminase deficiency
Retroviral insertion site
Severe combined immunodeficiency
Strimvelis

Additional relevant MeSH terms:
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Immune System Diseases