AzTrials
AzTrials

Immunologic Deficiency SyndromesNCT03478670

Strimvelis Registry Study to Follow-up Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)

An observational study of Immunologic Deficiency Syndromes, run by Fondazione Telethon at 1 site in Italy.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial summary

Adenosine deaminase (ADA) enzyme deficiency results in severe combined immunodeficiency (SCID), a fatal autosomal recessive inherited immune disorder. Strimvelis (or GSK2696273) is a gene therapy intended for patients with ADA-SCID and for whom no suitable human leukocyte antigen (HLA) matched related stem cell donor… Read more about this study

Who is it for?
Any age
Conditions the study is for
Immunologic Deficiency Syndromes
What is being tested?
Strimvelis
Type of treatment
Injection or infusion
How many people
50 participants
Where
1 siteItaly
Study dates
5 May 2017to 31 Dec 2045
How long will I take part?
15 Years
Phase
Observational
Are there results?
Not yet: the study is under way

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

Study population: This registry will include all subjects who have received Strimvelis (or GSK2696273) or mPB-GT and consented to participate in the registry. A target number of 50 subjects will be enrolled in the registry.

Who may be able to join

  • Patients with ADA-SCID, treated with Strimvelis™ or GSK2696273, as part of its clinical development program or mPB-GT.
  • Adult patients, or patients for whom their parents or legal guardians have signed the informed consent form for participation in the registry.
  • There are no formal exclusion criteria for participation as this registry will follow all patients who have received Strimvelis™ or GSK2696273, or mPB-GT prior to enrollment, subject to informed consent.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Italy1 site

  • Ospedale San Raffaele

    Milan, Lombardy, 20132

Other trials in Italy

About this study

Official title: Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID) Registry for Patients Treated With Strimvelis (Previously GSK2696273) Gene Therapy: Long-Term Prospective, Non-Interventional Follow-up of Safety and Effectiveness

Adenosine deaminase (ADA) enzyme deficiency results in severe combined immunodeficiency (SCID), a fatal autosomal recessive inherited immune disorder. Strimvelis (or GSK2696273) is a gene therapy intended for patients with ADA-SCID and for whom no suitable human leukocyte antigen (HLA) matched related stem cell donor is available. This therapy aims to restore ADA function in hematopoietic cell lineages, and in doing so prevents the pathology caused by purine metabolites (i.e., impaired immune function). This registry evaluates the long term safety and effectiveness outcomes of subjects who have received Strimvelis and is conducted as a post approval safety study associated with EMA marketing authorisation of Strimvelis™. In this study will be also included patients for whom the gene therapy medicinal product has been prepared starting from mobilized peripheral blood (mPB)-derived CD34+ cells (mPB-GT).

Read the detailed description

This is a prospective and retrospective, non-interventional follow-up registry of patients with ADA-SCID treated with Strimvelis™. The registry does not have a comparator group and the product will have been given on a single occasion prior to entering this registry. Safety and effectiveness will be assessed for a target number of 50 patients who will have received Strimvelis™ or GSK2696273 or mPB-GT. The end of enrollment will be after the recruitment of the 50th patient and the registry will close when the 50th patient finishes the 15- year follow-up.

Being tested
Strimvelis
Keywords
gene therapy, retroviral vector, inherited immune disorder, ADA-SCID, previously GSK2696273, Strimvelis
Medical subject headings
Immunologic Deficiency Syndromes, Severe combined immunodeficiency due to adenosine deaminase deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • StrimvelisGenetic

    Strimvelis is a CD34+ cell enriched dispersion of human autologous bone marrow derived hematopoietic stem/progenitor cells transduced with a retroviral vector containing the human ADA gene. It will be administered as an intravenous infusion once only.

    In this study will be also included patients for whom the gene therapy medicinal product has been prepared starting from mobilized peripheral blood (mPB)-derived CD34+ cells, treated under hospital exemption (HE) frame, according to the Italian Decree of the Ministry of Health, January 16th 2015, "Provisions on advanced therapy drugs prepared on a non-repetitive basis".

Study groups in NCT03478670
Study groupRoleWhat they receive
ADA-SCID subjects treated with StrimvelisSubjects with ADA-SCID who have received Strimvelis (previously GSK2696273) gene therapy, comprising patients treated prior to marketing authorisation (i.e. clinical studies and compassionate use programs) and those treated after marketing authorisation. In this study will be also included patients for whom the gene therapy medicinal product has been prepared starting from mobilized peripheral blood (mPB)-derived CD34+ cells, treated under hospital exemption (HE) frame, according to the Italian Decree of the Ministry of Health, January 16th 2015, "Provisions on advanced therapy drugs prepared on a non-repetitive basis".
Receives: Genetic: Strimvelis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of adverse events of special interest

    The following adverse events of interest will be evaluated:

    • AEs and SAEs related to medical or surgical procedures associated with Strimvelis™ administration (e.g. central venous catheter, busulfan conditioning).
    • Oncogenesis.
    • Autoimmunity/autoinflammatory events.
    • Unsuccessful response to gene therapy.
    • Risks related to short shelf-life of product.
    • Non-immunologic manifestations of ADA-SCID (e.g. hepatic steatosis, cognitive defects, behavioral abnormalities, hearing impairment).
    • Risks related to residuals present in the drug product administered to the patient.
    • Hypersensitivity to the product.
    • Replication competent retrovirus.

    The number (%) of patients experiencing AESIs in each of these categories along with the number of events will be summarized by System Organ Class (SOC) and Preferred Term (PT).

    Measured: Up to 15 years

  2. Frequency of reported AEs and SAEs/ADRs

    The number (%) of patients experiencing AEs along with the number of events will be summarized by System Organ Class (SOC) and Preferred Term (PT).

    • overall;
    • by severity grade;
    • AEs grade 3 or higher;
    • AEs related to treatment;
    • SAEs;
    • SAEs grade 3 or higher;
    • SAEs related to treatment;
    • AEs leading to study discontinuation. These summaries will be repeated for the rate of events per person year.

    Measured: Up to 15 years

  3. Actual values of laboratory blood test results (i.e. biochemistry, haematology) at each annual visits.

    The baseline evaluation for each parameter will be the final evaluation prior to treatment with Strimvelis™.

    For each parameter, the actual value will be summarized at each annual visit using descriptive statistics.

    Laboratory evaluations will be flagged against the normal range as low/normal/high. For each parameter, the number (%) of subjects with evaluations that were low/normal/high relative to the normal range will be summarized by annual visit. Out of range values will be assessed for their clinical significance. For each parameter, the number (%) of subjects with clinically significant evaluations will be summarized by annual visit and at any time post-treatment.

    Measured: At each annual visit up to 15 years

  4. Number (%) of subjects with fertility and positive pregnancy outcomes

    Fertility and pregnancy related outcomes will be listed and/or summarised as appropriate. Number (%) of subjects with fertility and pregnancy outcome will be reported. If the registry remains open after an individual patient has been followed for 15 years post treatment, fertility and pregnancy related events and outcomes will continue to be solicited or spontaneously reported, every 2 years until the registry closes.

    Measured: Up to 15 years

  5. The number (%) of subjects with an abnormal retroviral insertion site (RIS) analysis.

    Data from RIS will be collected only if an HCP has performed these tests (e.g. following suspected malignancy or after a diagnosis of malignancy). The number (%) of subjects with an abnormal result will be summarized.

    Measured: Up to 15 years.

Secondary outcomes (11)

  1. Overall Survival

    Number and cause of deaths and time to onset of fatal events will be summarised. Starting time will be the date of therapy administration.

    Measured: Up to 15 years

  2. Event (Intervention) free survival

    Event (Intervention) free survival will be evaluated using the time in years from treatment with Strimvelis to either the first intervention (Hematopoietic Stem Cell Transplant or >3 months of Enzyme Replacement Therapy). Summary statistics, proportions and rates will be provided.

    Measured: Up to 15 years.

  3. The number (%) of subjects requiring use of treatments of interest

    The medications/treatments of interest in this study are ERT, HSCT, Immunoglobulins, radiotherapy and cytotoxic agents. Categorical responses for whether subjects have received these treatments are captured per annual visit. The number (%) of subjects requiring each of these treatments and any of these treatments will be summarized at each annual visit throughout the follow-up period and overall. For ERT, the duration of treatment and number of patients requiring more than three months of continuous treatment will be summarized.

    Measured: Up to 15 years.

  4. Immune reconstitution

    Peripheral lymphocytes and T cell function from response to mitogens will be evaluated. Actual counts and the change from baseline will be summarized at each annual visit using summary statistics (n, mean, 95% CI, SD, geometric mean, (gCV), minimum, median, maximum).

    Measured: Baseline and annually up to 15 years.

  5. Growth

    Growth (i.e. height and weight) percentiles will be calculated and compared to World Health Organisation (WHO) standard growth charts.

    Measured: Up to 15 years.

  6. Systemic metabolite detoxification

    Systemic metabolite detoxification will be assessed using dAXP levels in RBCs and ADA activity in plasma, RBCs and lymphocytes. Actual values and the change from baseline will be summarized at each annual visit using summary statistics (n, mean, 95% CI, SD, geometric mean, gCV, minimum, median, maximum). The geometric mean and 95% CI will be plotted over time. In addition, individual plots over time will be produced.

    Adequate ADA activity is defined as a level of >= 210 nmol/h/mg, adequate dAXP in RBC is defined as < 100 nmol/mL. The number (%) of patients with adequate levels of ADA activity and dAXP will be summarized.

    Measured: Baseline and annually up to 15 years.

  7. Vector copy number, measured in PBMCs (peripheral blood mononuclear cells) and subpopulations.

    Vector copy number (VCN) will be measured in PBMCs and and subpopulations CD3+, CD4+, CD8+, CD19+, CD15+ and CD56+ cells and summarized. VCN will be summarized by visit using summary statistics (n, mean, 95% CI, SD, geometric mean, gCV, minimum, median, maximum).

    Measured: Up to 15 years.

  8. Number and proportion of patients with severe infections, and associated length of stay

    Severe infections, defined as infections requiring hospitalization or prolonging hospitalization, will be identified from the adverse event data. The rate of infection will be calculated as number of severe infections divided by the person-years of observation after treatment with Strimvelis™.

    The cumulative number (%) of patients with severe infections and the cumulative rate of severe infections will be presented at each year post treatment along their 95% CI.

    Measured: Up to 15 years.

  9. The number (%) of subjects falling into each category for pediatric development and quality of life assessments

    Pediatric development assessments will include:

    • whether the child is attending a school appropriate for age
    • whether the child is in an age-appropriate grade/class at school
    • whether the child requires special educational support (e.g. dedicated tutor)
    • participation in sports as desired by child
    • requirement for hearing aid(s)
    • impact of the child's health on the guardian's employment. For each of these assessments, the number (%) of subjects falling into each category for these assessments will be summarized over time. For Karnofsky and Lansky scores, the actual value and change from baseline will be summarized at each annual visit using descriptive statistics.

    Measured: Up to 15 years.

  10. Patient (or proxy) reported Peds-QL

    Data from patient (or proxy) reported outcome measures and development questionnaires [e.g. Peds-QL] where they are used routinely as part of a physician's standard of care or where permitted by local authorities as non-interventional assessments, will also be summarised. Absolute scores will be calculated.

    Measured: Up to 15 years.

  11. Response to childhood vaccinations

    Response to vaccinations against tetanus toxoid, diphtheria, pertussis, hepatitis B, hemophilius influenzae B (HIB), pneumococcus and measles, mumps and rubella (MMR) will be assessed.

    The number of subjects receiving each vaccination and any vaccination will be summarized along with the number (%) of those subjects with a positive response. The exact binomial 95% confidence interval will be provided for each response category of each vaccination type.

    Measured: Up to 15 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2018
  2. Study start5 May 2017
  3. Primary completion31 Dec 2045 (estimated)
  4. Study completion31 Dec 2045 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Other
Enrolment
50 participants (estimated)
Target duration
15 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT03478670
Sponsor's protocol ID
STRIM-003
Status last verified
May 2026
First submitted
23 Mar 2018
Last updated
22 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Migliavacca M, Barzaghi F, Fossati C, Rancoita PMV, Gabaldo M, Dionisio F, Giannelli S, Salerio FA, Ferrua F, Tucci F, Calbi V, Gallo V, Recupero S, Consiglieri G, Pajno R, Sambuco M, Priolo A, Ferri C, Garella V, Monti I, Silvani P, Darin S, Casiraghi M, Corti A, Zancan S, Levi M, Cesana D, Carlucci F, Pituch-Noworolska A, AbdElaziz D, Baumann U, Finocchi A, Cancrini C, Ladogana S, Meinhardt A, Meyts I, Montin D, Notarangelo LD, Porta F, Pasquet M, Speckmann C, Stepensky P, Tommasini A, Rabusin M, Karakas Z, Galicchio M, Leonardi L, Duse M, Guner SN, Di Serio C, Ciceri F, Bernardo ME, Aiuti A, Cicalese MP. Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency. Nat Med. 2024 Feb;30(2):488-497. doi: 10.1038/s41591-023-02789-4. Epub 2024 Feb 14.

    PubMed 38355973

Questions about this trial

What is this clinical trial studying?

An observational study of Immunologic Deficiency Syndromes, run by Fondazione Telethon at 1 site in Italy.

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 3 inclusion and 0 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: enrolling by invitation, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Frequency of adverse events of special interest (time frame: Up to 15 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03478670, which also lists 1 linked publication.

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 22 May 2026; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in