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Trial record 88 of 79742 for:    subjects

Long-term Follow-up of Subjects Treated With OTL-300 for Transfusion Dependent Beta-thalassemia Study (TIGET-BTHAL)

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ClinicalTrials.gov Identifier: NCT03275051
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : April 22, 2019
Sponsor:
Collaborator:
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Information provided by (Responsible Party):
Orchard Therapeutics

Brief Summary:
OTL-300 is a gene therapy drug product consisting of autologous hematopoietic stem/progenitor cluster of differentiation (CD) 34+ cells genetically modified with a lentiviral vector (GLOBE) encoding the human beta globin gene. The TIGET-BTHAL is a phase I/II study evaluating safety and efficacy of OTL-300 in subjects with transfusion dependent beta-thalassemia for two years post gene-therapy. Subjects with rare disease who have undergone gene therapy are followed for efficacy and possible delayed adverse events. Thus, this study is designed to follow patients who have received gene therapy on TIGET-BTHAL for an additional six years (for a total of eight years).

Condition or disease Intervention/treatment Phase
Beta Thalassaemia Other: Safety and Efficacy assessments Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Intervention Model Description: No study treatment will be administered in this study. Subjects who have received treatment with OTL-300 in and completed study TIGET-BTHAL will be included in this study.
Masking: None (Open Label)
Masking Description: No study treatment will be administered.
Primary Purpose: Other
Official Title: A Long-term Safety and Efficacy follow-on Study in Participants With Transfusion Dependent Beta-thalassemia Who Have Previously Received OTL-300 (Formerly Know as GSK2696277)) and Completed the TIGET-BTHAL Study
Actual Study Start Date : October 4, 2017
Estimated Primary Completion Date : December 1, 2025
Estimated Study Completion Date : June 1, 2026


Arm Intervention/treatment
Experimental: All subjects
Subjects who have received treatment with OTL-300 in and completed study TIGET-BTHAL will be included in this study. Subjects received OTL-300 injection administered intraosseously in TIGET-BTHAL study. No study treatment will be administered in this study (207757).
Other: Safety and Efficacy assessments
Safety and efficacy assessment of OTL-300 in subjects with transfusion dependent beta-thalassemia will be performed.




Primary Outcome Measures :
  1. Number of subjects with absence of abnormal clonal proliferation (ACP) [ Time Frame: Up to 6 years ]
    Clonal proliferation describes the selection and reproduction of only one type of cell.

  2. Number of subjects with Polyclonal engraftment [ Time Frame: Up to 6 years ]
    Integration site analysis will be performed on different hematopoietic lineages from peripheral blood and/or bone marrow. Polyclonality of hematopoiesis is defined as >1000 unique integration sites retrieved at specified time points. The number of subjects with polyclonality of hematopoiesis will be estimated.


Secondary Outcome Measures :
  1. Number of subjects with reduction in red blood cells (RBC) transfusion volume [ Time Frame: Up to 6 years ]
  2. Number of subjects with reduction in transfusion rate up to transfusion independence [ Time Frame: Up to 6 years ]
  3. Number of subjects with transfusion independence [ Time Frame: Up to 6 years ]
    Transfusion independence is defined as <= 1 transfusion in the previous 6 months.

  4. Hemoglobin (Hb) levels in subjects achieving transfusion independence [ Time Frame: Up to 6 years ]
  5. Number of subjects with sustained engraftment of genetically corrected cells [ Time Frame: Up to 6 years ]
    Engraftment will be assessed by vector-specific quantitative polymerase chain reaction (PCR) on bone marrow. Sustained engraftment is defined as >=0.15 vector copy number (VCN)/genome in bone marrow erythroid cells.

  6. Number of subjects with overall survival [ Time Frame: Up to 6 years ]
    The number of subjects alive over all the trial.

  7. Number of subjects with adverse events (AEs), serious AEs (SAEs) [ Time Frame: Up to 6 years ]
  8. Clinical chemistry laboratory parameters as a measure of safety [ Time Frame: Up to 6 years ]
  9. Hematology laboratory parameters as a measure of safety [ Time Frame: Up to 6 years ]
  10. Urinalysis as a measure of safety [ Time Frame: Up to 6 years ]
  11. Occurrence of viral infections as a measure of safety [ Time Frame: Up to 6 years ]
    Microbiological laboratory tests will be performed to analyze the presence of hepatitis C virus ribonucleic acid (RNA), hepatitis B virus RNA, hepatitis B surface antigen, human T cell lymphotropic virus type 1-2 antibodies. Molecular tests will be performed for human immunodeficiency virus in peripheral blood or plasma.

  12. Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety [ Time Frame: Up to 6 years ]
    Immunological laboratory tests will be performed to analyze antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1-2, varicella zoster virus, toxoplasma.

  13. Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores [ Time Frame: Up to 6 years ]
  14. Short-Form-36 (SF-36) scores [ Time Frame: Up to 6 years ]
    Impact of disease on overall QoL in adults will be measured using the SF-36.

  15. Pediatric Quality of Life (PedsQL) questionnaire scores [ Time Frame: Up to 6 years ]
    The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.

  16. Evaluation of growth in pediatric subjects [ Time Frame: Up to 6 years ]
    Growth will be assessed by changes in height versus national growth charts and predicted genetic height.

  17. Assessment of hormonal levels in pediatric subjects [ Time Frame: Up to 6 years ]
  18. Changes in puberty status as assessed by clinical examination [ Time Frame: Up to 6 years ]
  19. Changes in puberty status as assessed by Tanner scale (TS) [ Time Frame: Up to 6 years ]
    Puberty will be assessed using TS.

  20. Changes in puberty status as assessed by general questioning [ Time Frame: Up to 6 years ]


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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have completed study TIGET-BTHAL i.e. who have received treatment and been followed for two years post treatment with OTL-300.
  • For adults; capable of giving signed informed consent. For children; informed assent and/or consent in writing signed by the subject and/or parent(s) / legal representative (according to local regulations and age of the subject).

Exclusion Criteria:

  • None

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 ClinicalTrials.gov identifier (NCT number): NCT03275051


Contacts
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Contact: Orchard Clinical Trials +44 (0) 20 3808 8286 medinfo@orchard-tx.com

Locations
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Italy
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET) Recruiting
Milan, Italy, 20132
Contact: Orchard Clinical Trials    +44 (0) 20 3808 8286      
Contact       medinfo@orchard-tx.com   
Sponsors and Collaborators
Orchard Therapeutics
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Investigators
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Principal Investigator: Orchard Clinical Trials Ospedale San Raffaele- Telething Institute for Gene Therapy (SR-TIGET)

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Responsible Party: Orchard Therapeutics
ClinicalTrials.gov Identifier: NCT03275051     History of Changes
Other Study ID Numbers: 207757
2017-001366-14 ( EudraCT Number )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019

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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:
Beta Thalassaemia
previously GSK2696277
Lentiviral vector
TIGET-BTHAL
Gene therapy

Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn