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

Primary Purpose

Beta Thalassaemia

Status

Active

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

Safety and Efficacy assessments

About this trial

This is an interventional other trial for Beta Thalassaemia focused on measuring Beta Thalassaemia, previously GSK2696277, Lentiviral vector, TIGET-BTHAL, Gene therapy

Eligibility Criteria

3 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All subjects

Arm Description

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).

Outcomes

Primary Outcome Measures

Number of subjects with absence of abnormal clonal proliferation (ACP)

Clonal proliferation describes the selection and reproduction of only one type of cell.

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.

Secondary Outcome Measures

Number of subjects with reduction in red blood cells (RBC) transfusion volume

Number of subjects with reduction in transfusion rate up to transfusion independence

Number of subjects with transfusion independence

Transfusion independence is defined as <= 1 transfusion in the previous 6 months.

Hemoglobin (Hb) levels in subjects achieving transfusion independence

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.

Number of subjects with overall survival

The number of subjects alive over all the trial.

Number of subjects with adverse events (AEs), serious AEs (SAEs)

Clinical chemistry laboratory parameters as a measure of safety

Hematology laboratory parameters as a measure of safety

Urinalysis as a measure of safety

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.

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.

Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores

Short-Form-36 (SF-36) scores

Impact of disease on overall QoL in adults will be measured using the SF-36.

Pediatric Quality of Life (PedsQL) questionnaire scores

The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.

Evaluation of growth in pediatric subjects

Growth will be assessed by changes in height versus national growth charts and predicted genetic height.

Assessment of hormonal levels in pediatric subjects

Changes in puberty status as assessed by clinical examination

Changes in puberty status as assessed by Tanner scale (TS)

Puberty will be assessed using TS.

Changes in puberty status as assessed by general questioning

Full Information

NCT ID

NCT03275051

First Posted

August 16, 2017

Last Updated

November 22, 2022

Sponsor

IRCCS San Raffaele

Collaborators

Telethon Institute for Gene Therapy (OSR-TIGET)

1. Study Identification

Unique Protocol Identification Number

NCT03275051

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

October 4, 2017 (Actual)

Primary Completion Date

December 1, 2025 (Anticipated)

Study Completion Date

June 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

IRCCS San Raffaele

Collaborators

Telethon Institute for Gene Therapy (OSR-TIGET)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Beta Thalassaemia

Keywords

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

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

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.

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

All subjects

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

Safety and Efficacy assessments

Intervention Description

Safety and efficacy assessment of OTL-300 in subjects with transfusion dependent beta-thalassemia will be performed.

Primary Outcome Measure Information:

Title

Number of subjects with absence of abnormal clonal proliferation (ACP)

Description

Clonal proliferation describes the selection and reproduction of only one type of cell.

Time Frame

Up to 6 years

Title

Number of subjects with Polyclonal engraftment

Description

Time Frame

Up to 6 years

Secondary Outcome Measure Information:

Title

Number of subjects with reduction in red blood cells (RBC) transfusion volume

Time Frame

Up to 6 years

Title

Number of subjects with reduction in transfusion rate up to transfusion independence

Time Frame

Up to 6 years

Title

Number of subjects with transfusion independence

Description

Transfusion independence is defined as <= 1 transfusion in the previous 6 months.

Time Frame

Up to 6 years

Title

Hemoglobin (Hb) levels in subjects achieving transfusion independence

Time Frame

Up to 6 years

Title

Number of subjects with sustained engraftment of genetically corrected cells

Description

Time Frame

Up to 6 years

Title

Number of subjects with overall survival

Description

The number of subjects alive over all the trial.

Time Frame

Up to 6 years

Title

Number of subjects with adverse events (AEs), serious AEs (SAEs)

Time Frame

Up to 6 years

Title

Clinical chemistry laboratory parameters as a measure of safety

Time Frame

Up to 6 years

Title

Hematology laboratory parameters as a measure of safety

Time Frame

Up to 6 years

Title

Urinalysis as a measure of safety

Time Frame

Up to 6 years

Title

Occurrence of viral infections as a measure of safety

Description

Time Frame

Up to 6 years

Title

Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety

Description

Immunological laboratory tests will be performed to analyze antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus 1-2, varicella zoster virus, toxoplasma.

Time Frame

Up to 6 years

Title

Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores

Time Frame

Up to 6 years

Title

Short-Form-36 (SF-36) scores

Description

Impact of disease on overall QoL in adults will be measured using the SF-36.

Time Frame

Up to 6 years

Title

Pediatric Quality of Life (PedsQL) questionnaire scores

Description

The PedsQL 4.0 generic core scale will be used to measure QoL in pediatric subjects.

Time Frame

Up to 6 years

Title

Evaluation of growth in pediatric subjects

Description

Growth will be assessed by changes in height versus national growth charts and predicted genetic height.

Time Frame

Up to 6 years

Title

Assessment of hormonal levels in pediatric subjects

Time Frame

Up to 6 years

Title

Changes in puberty status as assessed by clinical examination

Time Frame

Up to 6 years

Title

Changes in puberty status as assessed by Tanner scale (TS)

Description

Puberty will be assessed using TS.

Time Frame

Up to 6 years

Title

Changes in puberty status as assessed by general questioning

Time Frame

Up to 6 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Orchard Clinical Trials

Organizational Affiliation

Ospedale San Raffaele- Telething Institute for Gene Therapy (SR-TIGET)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)

City

Milan

ZIP/Postal Code

20132

Country

Italy

12. IPD Sharing Statement

Learn more about this trial

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

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