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

NCT03478670 | Enrolling By Invitation

• 1 other identifier: STRIM-003
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

Immunologic Deficiency Syndromes

Keywords

gene therapy; retroviral vector; inherited immune disorder; ADA-SCID; previously GSK2696273; Strimvelis

Outcome Measures

Primary Outcomes (5)

• 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).

  Up to 15 years

• 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.

  Up to 15 years

• 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.

  At each annual visit up to 15 years

• 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.

  Up to 15 years

• 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.

  Up to 15 years.

Secondary Outcomes (11)

• Overall Survival

  Up to 15 years

• Event (Intervention) free survival

  Up to 15 years.

• The number (%) of subjects requiring use of treatments of interest

  Up to 15 years.

• Immune reconstitution

  Baseline and annually up to 15 years.

• Growth

  Up to 15 years.

Study Arms (1)

ADA-SCID subjects treated with Strimvelis

Subjects 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".

Genetic: Strimvelis

Interventions

Strimvelis GENETIC

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".

ADA-SCID subjects treated with Strimvelis

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Telethon: lead

Study Sites (1)

Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Related Publications (1)

• 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.

  PMID: 38355973 DERIVED

MeSH Terms

Conditions

Immunologic Deficiency Syndromes; Severe combined immunodeficiency due to adenosine deaminase deficiency

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Fondazione Telethon

  Fondazione Telethon

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 15 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2018
• First Posted: March 27, 2018
• Study Start: May 5, 2017
• Primary Completion (Estimated): December 31, 2045
• Study Completion (Estimated): December 31, 2045
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

IT (1)