Long-Term Follow-up of Subjects With Transfusion-Dependant β-Thalassemia Treated With Ex Vivo Gene Therapy Using Autologous Hematopoietic Stem Cells Transduced With a Lentiviral Vector

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genetix Biotherapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 Oct 2008 → ongoing

Decision date (initial)

2024-09-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-513905-29-00

EudraCT number

2013-002245-11

ClinicalTrials.gov

NCT02633943

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy

- Monitor for long-term safety of the gene therapy drug product (i.e., the "drug product") used in bluebird bio-sponsored clinical studies (i.e., the "parent studies") in treated subjects with transfusion-dependent β6thalassemia (TDT)
- Monitor for long-term efficacy of the drug product

Secondary objectives 1

1. Not Applicable

Conditions and MedDRA coding

Beta-thalassaemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/ legal guardian(s)
2. Treated with drug product for therapy of transfusion-dependent β- thalassemia in a bluebird bio-sponsored clinical study

Exclusion criteria 1

1. There are no exclusion criteria for this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. The number of subjects with malignancies
2. The number of subjects with immune-related AEs (e.g., autoimmune disorders, GVHD, opportunistic infections, HIV)
3. The number of subjects with new or worsening hematologic disorders
4. The number of subjects with new or worsening neurologic disorders

Secondary endpoints 16

1. βA-T87Q-globin expression in peripheral blood over time post-drug product infusion through last follow-up, including Year 5, Year 10, and Year 15
2. Proportion of subjects who meet the definition of transfusion independence (TI), defined as a weighted average Hb ≥ 9 g/dL without any pRBC transfusions for a continuous period of ≥ 12 months at any time after drug product infusion in parent study and/or Study LTF-303
3. Proportion of subjects who meet the definition of TI at yearly timepoints including Year 5, Year 10, and Year 15 post-drug product infusion, and at last follow-up
4. Characterization of TI: Time from drug product infusion to achievement of TI (in parent study or Study LTF-303); Duration of TI; Weighted average Hb during T
5. Characterization of transfusion reduction (TR): Reduction in annualized pRBC transfusion volume (mL/kg/year) from 6 months post-drug product infusion (parent study) through last followup of at least 50%, 60%, 75%, 90%, or 100% as compared to the annualized pRBC transfusion volume during the 2 years prior to parent study enrollment
6. Characterization of transfusion reduction (TR):Annualized pRBC transfusion volume (mL/kg/year) and frequency (number/year) from 6 months post-drug product infusion (parent study) through last follow-up as compared to the annualized pRBC transfusion requirements during the 2 years prior to parent study enrollment
7. Characterization of transfusion reduction (TR): Time from drug product infusion to last pRBC transfusion (in parent study or Study LTF-303)
8. Characterization of transfusion reduction (TR): Time from last pRBC transfusion (in parent study or Study LTF-303) to last follow-up
9. Weighted average nadir Hb from 6 months post-drug product infusion (parent study) through last follow-up as compared to the weighted average nadir Hb during the 2 years prior to parent study enrollment
10. Unsupported total Hb levels over time through last follow-up, including Year 5, Year 10, and Year 15
11. Unsupported total Hb levels ≥ 10 g/dL, ≥ 11 g/dL, ≥ 12 g/dL, ≥ 13 g/dL, and ≥ 14 g/dL over time through last follow-up, including Year 5, Year 10, and Year 15
12. Iron burden over time and change from parent study baseline in iron burden at yearly timepoints through last follow-up, as measured by: Liver iron content by magnetic resonance imaging (MRI)/Superconducting Quantum Interference Device (SQUID) as available ; Cardiac T2* by MRI as available ; Serum ferritin
13. Chelation therapy use, including time from last use of chelation therapy to last follow-up and absence of chelation use for at least 6 months post-drug product infusion in parent study and/or Study LTF-303
14. Therapeutic phlebotomy use, including annualized frequency
15. Measures of dyserythropoiesis over time as compared to parent study baseline, assessed by the following parameters: Reticulocytes ; Nucleated RBCs
16. Health-related quality of life (HRQoL) over time as compared to parent study baseline, using the following validated tools as available and as appropriate: Pediatric Quality of Life Inventory (PedsQL) ; EuroQol-5D (EQ-5D; youth version, EQ-5D-Y) ; Short Form-36 (SF-36) v2 ; Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genetix Biotherapeutics Inc.

Sponsor organisation

Genetix Biotherapeutics Inc.

Address

455 Grand Union Boulevard

City

Somerville

Postcode

02145-1446

Country

United States

Scientific contact point

Organisation

Bluebird Bio Inc.

Contact name

Clinical Trial Information

Public contact point

Organisation

Bluebird Bio Inc.

Contact name

Clinical Trial Information

Third parties 10

Locations

4 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications