Skip to main content
MedPath Trial logoMedPath TrialMedPath Trial Home
Clinical Trials/NCT03207009
NCT03207009CompletedPhase 3

A Phase 3 Single Arm Study Evaluating the Efficacy and Safety of Gene Therapy in Subjects With Transfusion-dependent β-Thalassemia by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral βA-T87Q-Globin Vector in Subjects ≤50 Years of Age

Genetix Biotherapeutics Inc.16 sites in 6 countries19 target enrollmentStarted: June 8, 2017Last updated:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
Conditions
Interventions

Trial Snapshot

Phase
Phase 3
Status
Completed
Enrollment
19
Locations
16
Primary Endpoint
Percentage of Participants Who Have Achieved Transfusion Independence (TI)
Study OverviewStudy DesignEligibility CriteriaArms & InterventionsOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Study Overview

Brief Summary

This is a single-arm, multi-site, single-dose, Phase 3 study in approximately 18 participants less than or equal to (<=) 50 years of age with transfusion-dependent β-thalassemia (TDT), who have a β0/β0, β0/IVS-I-110, or IVS-I-110/IVS-I-110 genotype. The study will evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product.

Study Design

Study Type
Interventional
Allocation
Na
Intervention Model
Single Group
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
0 Years to 50 Years (Child, Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • •Participants less than or equal to (<=) 50 years of age at the time of consent or assent (as applicable), and able to provide written consent (adults, or legal guardians, as applicable) or assent (adolescents or children). Provided that the data monitoring committee (DMC) has approved enrolling participants younger than 5 years of age, participants younger than 5 years of age may be enrolled if they weigh a minimum of 6 kilograms (kg) and are reasonably anticipated to be able to provide at least the minimum number of cells required to initiate the manufacturing process.
  • •Diagnosis of TDT with a history of at least 100 milliliter per kilogram per year (mL/kg/year) of pRBCs in the 2 years preceding enrollment (all participants), or be managed under standard thalassemia guidelines with >= 8 transfusions of pRBCs per year in the 2 years preceding enrollment (participants >=12 years).
  • •Clinically stable and eligible to undergo HSCT.
  • •Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Exclusion Criteria

  • •Presence of a mutation characterized as other then β0 (e.g., β+, βE, βC) on at least one β-globin gene (HBB) allele.
  • •Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B virus (HBV), or hepatitis C (HCV).
  • •A white blood cell (WBC) count less than (<) 3×10^9/liter (L), and/or platelet count <100×10^9/L not related to hypersplenism.
  • •Uncorrected bleeding disorder.
  • •Any prior or current malignancy.
  • •Prior HSCT.
  • •Advanced liver disease.
  • •A cardiac T2* <10 ms by MRI.
  • •Any other evidence of severe iron overload that, in the investigator's opinion, warrants exclusion.
  • •Participation in another clinical study with an investigational drug within 30 days of Screening.
  • •Any other condition that would render the participant ineligible for HSCT, as determined by the attending transplant physician or investigator.
  • •Prior receipt of gene therapy.
  • •Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile participant.
  • •A known and available human leukocyte antigen (HLA) matched family donor.
  • •Any contraindications to the use of granulocyte colony stimulating factor (G-CSF) and plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.

Arms & Interventions

LentiGlobin BB305 Drug Product

Experimental

LentiGlobin BB305 Drug Product (autologous CD34+ cell-enriched population that contains cells transduced with LentiGlobin BB305 lentiviral vector encoding human βA-T87Q-globin)

Intervention: LentiGlobin BB305 Drug Product (Genetic)

Outcomes

Primary Outcomes

Percentage of Participants Who Have Achieved Transfusion Independence (TI)

Time Frame: From 12 to 24 months post-transplant

TI was defined as a weighted average hemoglobin (Hb) \>= 9 grams per deciliter (g/dL) without any packed red blood cell (pRBC) transfusions for a continuous period of \>= 12 months at any time during the study after drug product infusion.

Secondary Outcomes

  • Duration of Transfusion Independence (TI)(From start of TI up to Month 24 (actual maximum time frame of up to approximately 25 months due to visit window))
  • Time From Drug Product Infusion to Achievement of Transfusion Independence (TI)(From drug product infusion to start of TI (up to Month 24 [actual maximum time frame of up to approximately 25 months due to visit window]))
  • Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24(Baseline, Month 12 and 24)
  • Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24(Baseline, Months 12 and 24)
  • Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume(12 months post-drug product infusion through Month 24)
  • Time From Drug Product Infusion to Last pRBC Transfusion(From start of drug product infusion up to Month 24)
  • Number of Participants Who Used Therapeutic Phlebotomy Post Drug Product Infusion(From drug product infusion through Month 24)
  • Annualized Phlebotomy Therapy Usage Following Drug Product Infusion(From drug product infusion through Month 24)
  • Change From Baseline in Serum Ferritin(Baseline, Month 12 and 24)
  • Percentage of Participants Who Have Achieved Transfusion Independence (TI) at Month 24(At Month 24 post-transplant)
  • Time From Last pRBC Transfusion to 24 Months(From last pRBC Transfusion up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window))
  • Weighted Average Nadir Hemoglobin (Hb)(12 months post-drug product infusion through Month 24)
  • Number of Participants With Unsupported Total Hb Levels (>=10 g/dL, >=11 g/dL, >=12 g/dL, >=13 g/dL, and >=14 g/dL) at Months 6, 9, 12, 18 and 24(At Months 6, 9, 12, 18 and 24)
  • Change From Baseline in Cardiac T2* on MRI(Baseline, Months 12 and 24)
  • Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24(Baseline, Months 12 and 24)
  • Percentage of Participants Who Meet the Definition of Transfusion Reduction (TR)(From 12 to 24 months post-transplant)
  • Annualized Number of pRBC Transfusions(From 12 months post-drug product infusion through Month 24)
  • Time From Last Iron Chelation Use to Last Follow-up(From last Iron Chelation up to Month 24 (actual maximum time frame of up to approximately 29 months due to visit window))
  • Change From Baseline in Liver Iron Content by Magnetic Resonance Imaging (MRI)(Baseline, Month 12 and 24)
  • Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Total Score(Baseline, Months 12 and 24)
  • Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI)(Timeframe varied by subject. For a given subject, the endpoint was calculated from 60 days after the last pRBC transfusion (so transfused blood did not confound the weighted average calculation) through the Month 24 Visit for that subject.)
  • Annualized Volume of pRBC Transfusions(From 12 to 24 months post-transplant)
  • Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24(At Month 6, 9, 12, 18 and 24)
  • Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion(From 6 to 24 months)
  • Change From Baseline in Short Form-36 Health Survey (SF-36), Version 2, Acute (Physical and Mental Component Summary Scores) at Months 12 and 24(Baseline, Months 12 and 24)

Investigators

Sponsor Class
Industry
Responsible Party
Sponsor

Study Sites (16)

Loading locations...

Similar Trials

Completed
Phase 3
A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia, Who do Not Have a β0/β0 GenotypeBeta-Thalassemia
NCT02906202Genetix Biotherapeutics Inc.24
Withdrawn
Phase 3
A Study of the Efficacy and Safety of MT1621 in Thymidine Kinase 2 (TK2) Deficiency (Treatment naïve)Thymidine Kinase 2 Deficiency
NCT04581733Zogenix MDS, Inc.
Active, not recruiting
Phase 1
AThis study will enroll subjects with transfusion dependent beta-thalassemia, who have a beta0/beta0 genotype, defined by a history of at least 100 mL/kg/year of packed red blood cells (pRBCs) or = 8 transfusions of pRBCs per year in the 2 year preceding enrollment.MedDRA version: 20.1Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 100000004850
EUCTR2016-003611-35-DEbluebird bio, Inc.18
Active, not recruiting
Phase 1
A
EUCTR2015-004122-33-DEbluebird bio, Inc.23
Active, not recruiting
Phase 1
AThis study will enroll subjects with transfusion-dependent beta-thalassemia, who have a beta0/beta0 genotype, defined by a history of at least 100 mL/kg/year of packed red blood cells (pRBCs) or = 8 transfusions of pRBCs per year in the 2 years preceding enrollment.MedDRA version: 20.1Level: LLTClassification code 10054660Term: Thalassemia betaSystem Organ Class: 100000004850
EUCTR2016-003611-35-FRbluebird bio, Inc.15