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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Beta Thalassaemia
• Intervention / Treatment: Other: Safety and Efficacy assessments

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with absence of abnormal clonal proliferation (ACP)	Clonal proliferation describes the selection and reproduction of only one type of cell.	Up to 6 years
Number of subjects with Polyclonal engraftment	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.	Up to 6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Transfusion independence is defined as <= 1 transfusion in the previous 6 months.	Up to 6 years
Hemoglobin (Hb) levels in subjects achieving transfusion independence		Up to 6 years
Number of subjects with sustained engraftment of genetically corrected cells	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.	Up to 6 years
Number of subjects with overall survival	The number of subjects alive over all the trial.	Up to 6 years
Number of subjects with adverse events (AEs), serious AEs (SAEs)		Up to 6 years
Clinical chemistry laboratory parameters as a measure of safety		Up to 6 years
Hematology laboratory parameters as a measure of safety		Up to 6 years
Urinalysis as a measure of safety		Up to 6 years
Occurrence of viral infections as a measure of safety	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.	Up to 6 years
Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety	Immunological laboratory tests will be performed to analyze antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1-2, varicella zoster virus, toxoplasma.	Up to 6 years
Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores		Up to 6 years
Short-Form-36 (SF-36) scores	Impact of disease on overall QoL in adults will be measured using the SF-36.	Up to 6 years
Pediatric Quality of Life (PedsQL) questionnaire scores	The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.	Up to 6 years
Evaluation of growth in pediatric subjects	Growth will be assessed by changes in height versus national growth charts and predicted genetic height.	Up to 6 years
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)	Puberty will be assessed using TS.	Up to 6 years
Changes in puberty status as assessed by general questioning		Up to 6 years

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Collaborators: Telethon Institute for Gene Therapy (OSR-TIGET)
• Investigators: Principal Investigator: Orchard Clinical Trials, Ospedale San Raffaele- Telething Institute for Gene Therapy (SR-TIGET)

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2017
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: August 16, 2017
• First Submitted That Met QC Criteria: September 5, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Actual): November 23, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Gene therapy; Lentiviral vector; Beta Thalassaemia; previously GSK2696277; TIGET-BTHAL
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: 207757; 2017-001366-14 (EudraCT Number)

Drug and device information, study documents

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