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

Study Overview
=================
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 will evaluate the long term safety and effectiveness outcomes of subjects who have received Strimvelis (or GSK2696273).

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

Conditions
-----------------
Immunologic Deficiency Syndromes

Intervention / Treatment
-----------------
* Genetic: Strimvelis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Subject with ADA-SCID, treated with Strimvelis or GSK2696273 as part of its clinical development program Adult subjects, or patients for whom their parents or legal guardians have signed the informed consent form for participation in the registry
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ADA-SCID subjects treated with Strimvelis<br>Subjects with ADA-SCID who have received Strimvelis (previously GSK2696273) gene therapy | Genetic: Strimvelis<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 21 years | 
| 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) | 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] | 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 & SAEs related to medical or surgical procedures, AEs & SAEs related to conditioning , hypersensitivity, autoimmunity, oncogenesis | Up to 15 years | 
| 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. | Up to 21 years | 
| 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 21 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
gene therapy, retroviral vector, inherited immune disorder, ADA-SCID, previously GSK2696273, Strimvelis