Strimvelis Registry Study to Follow-up Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)
- Conditions
- Immunologic Deficiency Syndromes
- Interventions
- Genetic: Strimvelis
- Registration Number
- NCT03478670
- Lead Sponsor
- Fondazione Telethon
- 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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description ADA-SCID subjects treated with Strimvelis 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).
- Primary Outcome Measures
Name Time Method Overall survival After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes Number and causes of death and time of onset of fatal events will be summarized. Starting time will be the date of therapy administration.
Absolute cluster of differentiation (CD)3+ T-cell for Immune reconstitution assessment Up to 15 years CD3+ T-cell counts will be assessed
Length of hospital stay Up to 15 years Duration of the hospitalization will be monitored
Number of subjects with the use of medications/treatments of interest Up to 15 years Subjects requiring ERT, HSCT, radiotherapy or cytotoxic agents will be assessed
Growth percentile in body weight Up to 15 years Subject's weight will be superimposed against gender specific WHO standard growth charts
Percentage of subjects with severe infections Up to 15 years Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization
Absolute CD19+ B-cell counts for Immune reconstitution assessment Up to 15 years CD19+ B-cell counts will be assessed
Vector copy number measured in peripheral blood mononuclear cells (PBMCs) Up to 15 years Vector copy number will be measured
Absolute peripheral lymphocyte for Immune reconstitution assessment Up to 15 years Peripheral lymphocyte will be assessed
Intervention free survival Up to 15 years Intervention is defined as hematopoietic stem cell transplantation (HSCT) or \>3 months of enzyme replacement therapy (ERT)
Phytohaemagglutinin (PHA) and anti CD-3 as a measure for T cell function Up to 15 years Phytohaemagglutinin (PHA) and anti CD-3 will be assessed
Growth percentile in body height Up to 15 years Subject's height will be superimposed against gender specific World Health Organization (WHO) standard growth charts
Deoxyadenosine nucleotides (dAXP) levels in red blood cells for the measurement of systemic metabolite detoxification Up to 15 years Deoxyadenosine nucleotides (dAXP) levels will be assessed in red blood cells
Number of subjects with adverse events of interest Up to 15 years (oncogenesis will continue to be solicited every 2 years until the registry closes) 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.
Number of subjects with fertility and pregnancy related outcomes After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes 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.
Number of subjects with severe infections Up to 15 years Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization
Scores for Ages and Stages Questionnaire-3[ASQ-3] Up to 15 years 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.
Number of subjects with non-immunological manifestations of ADA SCID Up to 15 years Subjects will be examined for hepatic steatosis, cognitive deficits, behavioural abnormalities including suspected or diagnosed attention deficit hyperactivity disorder, autism, or hearing impairment
Pediatric development and quality of life data Up to 15 years 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
Scores for Pediatric Quality of Life Questionnaire (Peds-QL) Up to 15 years 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.
Number of subjects with any adverse events (AEs) and any serious adverse events (SAEs) as a safety measure Up to 15 years 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
Number of subjects with abnormal clinical laboratory blood test results as a safety measure Up to 15 years Biochemistry, hematology and TSH parameters were assessed
Data from Retroviral Insertion Site (RIS) analysis and replication competent retrovirus (RCR) Up to 15 years RIS and RCR will be performed when suspected malignancy or after a diagnosis of malignancy
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy