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

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

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Immunologic Deficiency Syndromes
• Intervention / Treatment: Genetic: Strimvelis

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.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria

1. Patient with ADA-SCID, treated with Strimvelis™ or GSK2696273, as part of its clinical development program.
2. Adult patients, or patients for whom their parents or legal guardians have signed the informed consent form for participation in the registry.

There are no formal exclusion criteria for participation as this registry will follow all patients who have received Strimvelis™ prior to enrollment, subject to informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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 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

Collaborators and Investigators

• Sponsor: Fondazione Telethon
• Investigators: Study Director: Fondazione Telethon, Fondazione Telethon

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Estimated): May 31, 2037
• Study Completion (Estimated): May 31, 2037

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 23, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: gene therapy; ADA-SCID; retroviral vector; Strimvelis; inherited immune disorder; previously GSK2696273
• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Severe Combined Immunodeficiency
• Other Study ID Numbers: STRIM-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No