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).
This is a prospective, 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) 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). The registry will close to enrolment when 50 patients have been enrolled but will not close completely until the 50th patient finishes their 15 year follow-up.
Study Type
OBSERVATIONAL
Enrollment
50
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.
Ospedale San Raffaele
Milan, Lombardy, Italy
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.
Time frame: 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)
Time frame: 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
Time frame: Up to 15 years
Absolute peripheral lymphocyte for Immune reconstitution assessment
Peripheral lymphocyte will be assessed
Time frame: Up to 15 years
Absolute cluster of differentiation (CD)3+ T-cell for Immune reconstitution assessment
CD3+ T-cell counts will be assessed
Time frame: Up to 15 years
Absolute CD19+ B-cell counts for Immune reconstitution assessment
CD19+ B-cell counts will be assessed
Time frame: 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
Time frame: 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
Time frame: Up to 15 years
Growth percentile in body weight
Subject's weight will be superimposed against gender specific WHO standard growth charts
Time frame: 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
Time frame: Up to 15 years
Vector copy number measured in peripheral blood mononuclear cells (PBMCs)
Vector copy number will be measured
Time frame: Up to 15 years
Number of subjects with severe infections
Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization
Time frame: Up to 15 years
Percentage of subjects with severe infections
Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization
Time frame: Up to 15 years
Length of hospital stay
Duration of the hospitalization will be monitored
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: Up to 15 years
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