Immune System DiseasesPhase 4NCT03311074
Retroviral Insertion Site Methodology Study
A Phase 4 study testing Strimvelis in people with Immune System Diseases, run by Fondazione Telethon.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Immune System Diseases
- What is being tested?
- Strimvelis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 25 Jun 2020to 9 Jul 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: 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.
- Conditions
- Immune System Diseases
- Being tested
- Strimvelis
- Keywords
- Sonication Linker Medicated Polymerase Chain Reaction, Previously GSK2696273, Gene therapy, Adenosine deaminase deficiency, Retroviral insertion site, Severe combined immunodeficiency, Strimvelis
- Medical subject headings
- Immune System Diseases, Severe combined immunodeficiency due to adenosine deaminase deficiency, Severe Combined Immunodeficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
StrimvelisGenetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: Strimvelis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 5 years
Secondary outcomes (2)
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.
Measured: Up to 5 years
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.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2017
- Study start25 Jun 2020
- Primary completion9 Jul 2020
- Study completion9 Jul 2020
Why it stopped: Replaced with new observational study design
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune System DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- There will be no separate treatment groups in the study.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione Telethon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fondazione Telethon, Study director, Fondazione Telethon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03311074
- Sponsor's protocol ID
- STRIM-002
- Status last verified
- Nov 2023
- First submitted
- 11 Oct 2017
- Last updated
- 29 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Methodology Study to Investigate the Utility of Retroviral Insertion Site Analysis in Samples From Subjects Treated With Strimvelis™ Gene Therapy
- ClinicalTrials.gov ID
- NCT03311074
- Acronym / sponsor ID
- STRIM-002
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Replaced with new observational study design
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Fondazione TelethonUniversity, hospital or other
- Study start
- 25 Jun 2020 (actual)
- Primary completion
- 9 Jul 2020 (actual)
- Study completion
- 9 Jul 2020 (actual)
- First posted
- 16 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- There will be no separate treatment groups in the study.
| Arm | Type | Receives |
|---|---|---|
| Strimvelis treatment receivers | Experimental | Genetic: StrimvelisApproximately 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| StrimvelisStrimvelis 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. | Genetic | Strimvelis treatment receivers |
Primary outcome
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.
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.
2 secondary outcomes
Measurement of clone abundance of more than 5 percent
Time frame: Up to 5 years
Shannon diversity index measurement
Time frame: Up to 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fondazione Telethon study director
Fondazione Telethon
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Strimvelis in people with Immune System Diseases, run by Fondazione Telethon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 29 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean abundance measurement (time frame: Up to 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2024.