Long-term Follow-up of Subjects Treated With OTL-300 for Transfusion Dependent Beta-thalassemia Study (TIGET-BTHAL)
- Conditions
- Beta Thalassaemia
- Interventions
- Other: Safety and Efficacy assessments
- Registration Number
- NCT03275051
- Lead Sponsor
- IRCCS San Raffaele
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 9
- 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).
- None
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description All subjects Safety and Efficacy assessments 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).
- Primary Outcome Measures
Name Time Method Number of subjects with absence of abnormal clonal proliferation (ACP) Up to 6 years Clonal proliferation describes the selection and reproduction of only one type of cell.
Number of subjects with Polyclonal engraftment 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
Name Time Method Hematology laboratory parameters as a measure of safety Up to 6 years Urinalysis as a measure of safety Up to 6 years Hemoglobin (Hb) levels in subjects achieving transfusion independence Up to 6 years Clinical chemistry laboratory parameters as a measure of safety Up to 6 years Number of subjects with adverse events (AEs), serious AEs (SAEs) Up to 6 years Number of subjects with reduction in red blood cells (RBC) transfusion volume Up to 6 years Number of subjects with reduction in transfusion rate up to transfusion independence Up to 6 years Number of subjects with transfusion independence Up to 6 years Transfusion independence is defined as \<= 1 transfusion in the previous 6 months.
Number of subjects with sustained engraftment of genetically corrected cells 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.
Number of subjects with overall survival Up to 6 years The number of subjects alive over all the trial.
Occurrence of viral infections as a measure of safety 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.
Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety 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.
Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores Up to 6 years Short-Form-36 (SF-36) scores Up to 6 years Impact of disease on overall QoL in adults will be measured using the SF-36.
Pediatric Quality of Life (PedsQL) questionnaire scores Up to 6 years The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.
Evaluation of growth in pediatric subjects Up to 6 years Growth will be assessed by changes in height versus national growth charts and predicted genetic height.
Assessment of hormonal levels in pediatric subjects Up to 6 years Changes in puberty status as assessed by clinical examination Up to 6 years Changes in puberty status as assessed by Tanner scale (TS) Up to 6 years Puberty will be assessed using TS.
Changes in puberty status as assessed by general questioning Up to 6 years
Trial Locations
- Locations (1)
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
đŸ‡®đŸ‡¹Milan, Italy