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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03478670
Recruitment Status : Enrolling by invitation
First Posted : March 27, 2018
Last Update Posted : May 19, 2020
Information provided by (Responsible Party):
Orchard Therapeutics

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).

Condition or disease Intervention/treatment
Immunologic Deficiency Syndromes Genetic: Strimvelis

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 15 Years
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
Actual Study Start Date : March 31, 2017
Estimated Primary Completion Date : May 31, 2037
Estimated Study Completion Date : May 31, 2037

Group/Cohort Intervention/treatment
ADA-SCID subjects treated with Strimvelis
Subjects with ADA-SCID who have received Strimvelis (previously GSK2696273) gene therapy
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.

Primary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 21 years ]
    Number and causes of death and time of onset of fatal events will be summarized. Starting time will be the date of therapy administration.

  2. Intervention free survival [ Time Frame: Up to 15 years ]
    Intervention is defined as hematopoietic stem cell transplantation (HSCT) or >3 months of enzyme replacement therapy (ERT)

  3. Number of subjects with the use of medications/treatments of interest [ Time Frame: Up to 15 years ]
    Subjects requiring ERT, HSCT, radiotherapy or cytotoxic agents will be assessed

  4. Absolute peripheral lymphocyte for Immune reconstitution assessment [ Time Frame: Up to 15 years ]
    Peripheral lymphocyte will be assessed

  5. Absolute cluster of differentiation (CD)3+ T-cell for Immune reconstitution assessment [ Time Frame: Up to 15 years ]
    CD3+ T-cell counts will be assessed

  6. Absolute CD19+ B-cell counts for Immune reconstitution assessment [ Time Frame: Up to 15 years ]
    CD19+ B-cell counts will be assessed

  7. Phytohaemagglutinin (PHA) and anti CD-3 as a measure for T cell function [ Time Frame: Up to 15 years ]
    Phytohaemagglutinin (PHA) and anti CD-3 will be assessed

  8. Growth percentile in body height [ Time Frame: Up to 15 years ]
    Subject's height will be superimposed against gender specific World Health Organization (WHO) standard growth charts

  9. Growth percentile in body weight [ Time Frame: Up to 15 years ]
    Subject's weight will be superimposed against gender specific WHO standard growth charts

  10. Deoxyadenosine nucleotides (dAXP) levels in red blood cells for the measurement of systemic metabolite detoxification [ Time Frame: Up to 15 years ]
    Deoxyadenosine nucleotides (dAXP) levels will be assessed in red blood cells

  11. Vector copy number measured in peripheral blood mononuclear cells (PBMCs) [ Time Frame: Up to 15 years ]
    Vector copy number will be measured

  12. Number of subjects with severe infections [ Time Frame: Up to 15 years ]
    Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization

  13. Percentage of subjects with severe infections [ Time Frame: Up to 15 years ]
    Severe infection is defined as an infection requiring hospitalization or prolonging hospitalization

  14. Length of hospital stay [ Time Frame: Up to 15 years ]
    Duration of the hospitalization will be monitored

  15. Number of subjects with non-immunological manifestations of ADA SCID [ Time Frame: 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

  16. Pediatric development and quality of life data [ Time Frame: 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

  17. Scores for Pediatric Quality of Life Questionnaire (Peds-QL) [ Time Frame: Up to 15 years ]
    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

  18. Scores for Ages and Stages Questionnaire-3[ASQ-3] [ Time Frame: Up to 15 years ]
    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

  19. Number of subjects with adverse events of interest [ Time Frame: Up to 15 years ]
    AEs & SAEs related to medical or surgical procedures, AEs & SAEs related to conditioning , hypersensitivity, autoimmunity, oncogenesis

  20. Number of subjects with any adverse events (AEs) and any serious adverse events (SAEs) as a safety measure [ Time Frame: 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

  21. Number of subjects with abnormal clinical laboratory blood test results as a safety measure [ Time Frame: Up to 15 years ]
    Biochemistry, hematology and TSH parameters were assessed

  22. Number of subjects with fertility and pregnancy related outcomes [ Time Frame: Up to 21 years ]
    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.

  23. Data from Retroviral Insertion Site (RIS) analysis and replication competent retrovirus (RCR) [ Time Frame: Up to 21 years ]
    RIS and RCR will be performed when suspected malignancy or after a diagnosis of malignancy

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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 fifty subjects will be enrolled in the registry.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03478670

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Orchard Investigational Site
Milano, Lombardia, Italy, 20132
Sponsors and Collaborators
Orchard Therapeutics
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Study Director: Orchard Clinical Trials Orchard Therapeutics

Additional Information:

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Responsible Party: Orchard Therapeutics Identifier: NCT03478670    
Other Study ID Numbers: STRIM-003
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: May 19, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Orchard Therapeutics:
gene therapy
retroviral vector
inherited immune disorder
previously GSK2696273
Additional relevant MeSH terms:
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Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases