Beta ThalassaemiaNCT03275051
Long-term Follow-up of Subjects Treated With OTL-300 for Transfusion Dependent Beta-thalassemia Study (TIGET-BTHAL)
A study testing Safety and Efficacy assessments in people with Beta Thalassaemia, run by IRCCS San Raffaele at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Beta Thalassaemia
- What is being tested?
- Safety and Efficacy assessments
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteItaly
- Study dates
- 4 Oct 2017to 1 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
Italy1 site
Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Milan, 20132
About this study
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
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).
- Conditions
- Beta Thalassaemia
- Being tested
- Safety and Efficacy assessments
- Keywords
- Beta Thalassaemia, previously GSK2696277, Lentiviral vector, TIGET-BTHAL, Gene therapy
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Safety and Efficacy assessmentsOther
Safety and efficacy assessment of OTL-300 in subjects with transfusion dependent beta-thalassemia will be performed.
| Study group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | 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). Receives: Other: Safety and Efficacy assessments |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with absence of abnormal clonal proliferation (ACP)
Clonal proliferation describes the selection and reproduction of only one type of cell.
Measured: 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.
Measured: Up to 6 years
Secondary outcomes (20)
Number of subjects with reduction in red blood cells (RBC) transfusion volume
Measured: Up to 6 years
Number of subjects with reduction in transfusion rate up to transfusion independence
Measured: Up to 6 years
Number of subjects with transfusion independence
Transfusion independence is defined as <= 1 transfusion in the previous 6 months.
Measured: Up to 6 years
Hemoglobin (Hb) levels in subjects achieving transfusion independence
Measured: 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.
Measured: Up to 6 years
Number of subjects with overall survival
The number of subjects alive over all the trial.
Measured: Up to 6 years
Number of subjects with adverse events (AEs), serious AEs (SAEs)
Measured: Up to 6 years
Clinical chemistry laboratory parameters as a measure of safety
Measured: Up to 6 years
Hematology laboratory parameters as a measure of safety
Measured: Up to 6 years
Urinalysis as a measure of safety
Measured: 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.
Measured: 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.
Measured: Up to 6 years
Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 6 years
Assessment of hormonal levels in pediatric subjects
Measured: Up to 6 years
Changes in puberty status as assessed by clinical examination
Measured: Up to 6 years
Changes in puberty status as assessed by Tanner scale (TS)
Puberty will be assessed using TS.
Measured: Up to 6 years
Changes in puberty status as assessed by general questioning
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start4 Oct 2017
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Beta ThalassaemiaStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- Telethon Institute for Gene Therapy (OSR-TIGET)
- Responsible party
- Principal investigator, Alessandro Aiuti, IRCCS San Raffaele
- Investigators
- Orchard Clinical Trials, Principal investigator, Ospedale San Raffaele- Telething Institute for Gene Therapy (SR-TIGET)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03275051
- Sponsor's protocol ID
- 207757
- Other IDs
- 2017-001366-14, 2017
- Status last verified
- Nov 2022
- First submitted
- 16 Aug 2017
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03275051
- Acronym / sponsor ID
- 207757
- Conditions
- Beta Thalassaemia
- Keywords
- Beta Thalassaemia, previously GSK2696277, Lentiviral vector, TIGET-BTHAL, Gene therapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Collaborators
- Telethon Institute for Gene Therapy (OSR-TIGET)
- Study start
- 4 Oct 2017 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 7 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Other: Safety and Efficacy assessmentsSubjects 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). |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Safety and Efficacy assessmentsSafety and efficacy assessment of OTL-300 in subjects with transfusion dependent beta-thalassemia will be performed. | Other | All subjects |
Primary outcome
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.
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.
20 secondary outcomes
Number of subjects with reduction in red blood cells (RBC) transfusion volume
Time frame: Up to 6 years
Number of subjects with reduction in transfusion rate up to transfusion independence
Time frame: Up to 6 years
Number of subjects with transfusion independence
Time frame: Up to 6 years
Hemoglobin (Hb) levels in subjects achieving transfusion independence
Time frame: Up to 6 years
Number of subjects with sustained engraftment of genetically corrected cells
Time frame: Up to 6 years
Number of subjects with overall survival
Time frame: Up to 6 years
Number of subjects with adverse events (AEs), serious AEs (SAEs)
Time frame: Up to 6 years
Clinical chemistry laboratory parameters as a measure of safety
Time frame: Up to 6 years
Hematology laboratory parameters as a measure of safety
Time frame: Up to 6 years
Urinalysis as a measure of safety
Time frame: Up to 6 years
Occurrence of viral infections as a measure of safety
Time frame: Up to 6 years
Screening for occurrence of antibodies against viruses and toxoplasma as a measure of safety
Time frame: Up to 6 years
Functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) scores
Time frame: Up to 6 years
Short-Form-36 (SF-36) scores
Time frame: Up to 6 years
Pediatric Quality of Life (PedsQL) questionnaire scores
Time frame: Up to 6 years
Evaluation of growth in pediatric subjects
Time frame: Up to 6 years
Assessment of hormonal levels in pediatric subjects
Time frame: Up to 6 years
Changes in puberty status as assessed by clinical examination
Time frame: Up to 6 years
Changes in puberty status as assessed by Tanner scale (TS)
Time frame: Up to 6 years
Changes in puberty status as assessed by general questioning
Time frame: Up to 6 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2022.
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RecruitingObservational study
Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy
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Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
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A Study Evaluating the Efficacy and Safety of Mitapivat in Participants With Non-Transfusion-Dependent Alpha- or Beta-Thalassemia (α- or β-NTDT)
Non-Transfusion-dependent Alpha-Thalassemia, Non-Transfusion-dependent Beta-Thalassemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Orchard Clinical Trials principal investigator
Ospedale San Raffaele- Telething Institute for Gene Therapy (SR-TIGET)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Safety and Efficacy assessments in people with Beta Thalassaemia, run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with absence of abnormal clonal proliferation (ACP) (time frame: Up to 6 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2022.