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 (or GSK2696273).

Conditions

Immunologic Deficiency Syndromes

Keywords

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

Outcome Measures

Primary Outcomes (23)

• Overall survival

  Number and causes of death and time of onset of fatal events will be summarized. Starting time will be the date of therapy administration.

  After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes

• Intervention free survival

  Intervention is defined as hematopoietic stem cell transplantation (HSCT) or \>3 months of enzyme replacement therapy (ERT)

  Up to 15 years

• Number of subjects with the use of medications/treatments of interest

  Subjects requiring ERT, HSCT, radiotherapy or cytotoxic agents will be assessed

  Up to 15 years

• Absolute peripheral lymphocyte for Immune reconstitution assessment

  Peripheral lymphocyte will be assessed

  Up to 15 years

• Absolute cluster of differentiation (CD)3+ T-cell for Immune reconstitution assessment

  CD3+ T-cell counts will be assessed

  Up to 15 years

• Absolute CD19+ B-cell counts for Immune reconstitution assessment

  CD19+ B-cell counts will be assessed

  Up to 15 years

• Phytohaemagglutinin (PHA) and anti CD-3 as a measure for T cell function

  Phytohaemagglutinin (PHA) and anti CD-3 will be assessed

  Up to 15 years

• Growth percentile in body height

  Subject's height will be superimposed against gender specific World Health Organization (WHO) standard growth charts

  Up to 15 years

• Growth percentile in body weight

  Subject's weight will be superimposed against gender specific WHO standard growth charts

  Up to 15 years

• Deoxyadenosine nucleotides (dAXP) levels in red blood cells for the measurement of systemic metabolite detoxification

  Deoxyadenosine nucleotides (dAXP) levels will be assessed in red blood cells

  Up to 15 years

• Vector copy number measured in peripheral blood mononuclear cells (PBMCs)

  Vector copy number will be measured

  Up to 15 years

• Number of subjects with severe infections

  Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization

  Up to 15 years

• Percentage of subjects with severe infections

  Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization

  Up to 15 years

• Length of hospital stay

  Duration of the hospitalization will be monitored

  Up to 15 years

• Number of subjects with non-immunological manifestations of ADA SCID

  Subjects will be examined for hepatic steatosis, cognitive deficits, behavioural abnormalities including suspected or diagnosed attention deficit hyperactivity disorder, autism, or hearing impairment

  Up to 15 years

• Pediatric development and quality of life data

  Determination of attendance at school, if appropriate for age; whether the child is in an age appropriate grade/class at school; whether the child requires special educational support (example \[e.g.\] dedicated tutor); participation in sports as desired by child; requirement for hearing aid(s); adequate response to childhood vaccinations; severity of impact of a child's health on the guardian's intended employment and Karnofsky/Lansky performance status

  Up to 15 years

• Scores for Pediatric Quality of Life Questionnaire (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. The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population. It captures the following domains: general health/activities, feelings/emotional, social functioning, school functioning. Higher scores indicate better quality of life (QOL) for all domains of the Peds-QL. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. 4 dimensions (physical, emotional, social, \& school functioning) are scored.

  Up to 15 years

• Scores for Ages and Stages Questionnaire-3[ASQ-3]

  Where they are used routinely as part of a physician's standard of care or where permitted by local authorities as non-interventional assessments. The ASQ-3 includes a series of questions designed to assess 5 areas of development: communication, gross motor, fine motor, problem solving, and personal social. The questions target behaviours that are appropriate for particular developmental milestones.

  Up to 15 years

• Number of subjects with adverse events of interest

  AEs and SAEs related to medical or surgical procedures associated with Strimvelis™ administration (e.g. central venous catheter, busulfan conditioning); oncogenesis, autoimmunity, unsuccessful response to gene therapy, hypersensitivity to the product, risks related to residuals present in the drug product administered to the patient, risks related to short shelf-life of product, non-immunologic manifestations of ADA-SCID (e.g. hepatic steatosis, cognitive defects, behavioural abnormalities, hearing impairment), replication competent retrovirus.

  Up to 15 years (oncogenesis will continue to be solicited every 2 years until the registry closes)

• Number of subjects with any adverse events (AEs) and any serious adverse events (SAEs) as a safety measure

  AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE

  Up to 15 years

• Number of subjects with abnormal clinical laboratory blood test results as a safety measure

  Biochemistry, hematology and TSH parameters were assessed

  Up to 15 years

• Number of subjects with fertility and pregnancy related outcomes

  Labor and delivery information, full term pregnancy, caesarean section, abortion, miscarriage, ectopic, stillbirth rates will be assessed. Both male and female fertility issues will be analyzed.

  After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes

• Data from Retroviral Insertion Site (RIS) analysis and replication competent retrovirus (RCR)

  RIS and RCR will be performed when suspected malignancy or after a diagnosis of malignancy

  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 (including within compassionate use and early access programs).

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. This is an observational registry that includes all patients who have previously received Strimvelis™ or GSK2696273.

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) and consented to participate in the registry. A target number of 50 subjects will be enrolled in the registry.

You may qualify if:

• Patient with ADA-SCID, treated with Strimvelis™ or GSK2696273, as part of its clinical development program.
• 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: March 28, 2017
• Primary Completion (Estimated): May 31, 2037
• Study Completion (Estimated): May 31, 2037
• Last Updated: January 29, 2024

Record last verified: 2024-01

Locations

IT (1)