Clinical trial NCT03478670: Strimvelis Registry Study to Follow-up Patients With Adenosine Deaminase Severe Combined Immunodeficiency (ADA-SCID)
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
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Immunologic Deficiency Syndromes
Keywords: gene therapy
retroviral vector
inherited immune disorder
ADA-SCID
previously GSK2696273
Strimvelis
Lead sponsor: Fondazione Telethon
Sponsor class: OTHER
First posted: 2018-03-27
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes
measure: Intervention free survival
timeFrame: Up to 15 years
measure: Number of subjects with the use of medications/treatments of interest
timeFrame: Up to 15 years
measure: Absolute peripheral lymphocyte for Immune reconstitution assessment
timeFrame: Up to 15 years
measure: Absolute cluster of differentiation (CD)3+ T-cell for Immune reconstitution assessment
timeFrame: Up to 15 years
measure: Absolute CD19+ B-cell counts for Immune reconstitution assessment
timeFrame: Up to 15 years
measure: Phytohaemagglutinin (PHA) and anti CD-3 as a measure for T cell function
timeFrame: Up to 15 years
measure: Growth percentile in body height
timeFrame: Up to 15 years
measure: Growth percentile in body weight
timeFrame: Up to 15 years
measure: Deoxyadenosine nucleotides (dAXP) levels in red blood cells for the measurement of systemic metabolite detoxification
timeFrame: Up to 15 years
measure: Vector copy number measured in peripheral blood mononuclear cells (PBMCs)
timeFrame: Up to 15 years
measure: Number of subjects with severe infections
timeFrame: Up to 15 years
measure: Percentage of subjects with severe infections
timeFrame: Up to 15 years
measure: Length of hospital stay
timeFrame: Up to 15 years
measure: Number of subjects with non-immunological manifestations of ADA SCID
timeFrame: Up to 15 years
measure: Pediatric development and quality of life data
timeFrame: Up to 15 years
measure: Scores for Pediatric Quality of Life Questionnaire (Peds-QL)
timeFrame: Up to 15 years
measure: Scores for Ages and Stages Questionnaire-3[ASQ-3]
timeFrame: Up to 15 years
measure: Number of subjects with adverse events of interest
timeFrame: Up to 15 years (oncogenesis will continue to be solicited every 2 years until the registry closes)
measure: Number of subjects with any adverse events (AEs) and any serious adverse events (SAEs) as a safety measure
timeFrame: Up to 15 years
measure: Number of subjects with abnormal clinical laboratory blood test results as a safety measure
timeFrame: Up to 15 years
measure: Number of subjects with fertility and pregnancy related outcomes
timeFrame: After 15 years of follow-up, it will continue to be solicited every 2 years until the registry closes
measure: Data from Retroviral Insertion Site (RIS) analysis and replication competent retrovirus (RCR)
timeFrame: Up to 15 years
Secondary outcomes:
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
Study officials:
affiliation: Fondazione Telethon
name: Fondazione Telethon
role: STUDY_DIRECTOR
References: