Clinical trial NCT03207009: A Study Evaluating the Efficacy and Safety of the LentiGlobin® BB305 Drug Product in Participants With Transfusion-Dependent β-Thalassemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Beta-Thalassemia
Lead sponsor: bluebird bio
Sponsor class: INDUSTRY
First posted: 2017-07-02
Enrollment: 19
Sex: ALL
Minimum age (years): 0
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Have Achieved Transfusion Independence (TI)
timeFrame: From 12 to 24 months post-transplant
Secondary outcomes:
measure: Percentage of Participants Who Have Achieved Transfusion Independence (TI) at Month 24
timeFrame: At Month 24 post-transplant
measure: Duration of Transfusion Independence (TI)
timeFrame: From start of TI up to Month 24 (actual maximum time frame of up to approximately 25 months due to visit window)
measure: Time From Drug Product Infusion to Achievement of Transfusion Independence (TI)
timeFrame: 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])
measure: Weighted Average Hemoglobin (Hb) During Transfusion Independence (TI)
timeFrame: 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.
measure: Percentage of Participants Who Meet the Definition of Transfusion Reduction (TR)
timeFrame: From 12 to 24 months post-transplant
measure: Percentage of Participants Who Had a Reduction of At Least 50%, 60%, 75%, 90% or 100% in the Annualized pRBCs Transfusion Volume
timeFrame: 12 months post-drug product infusion through Month 24
measure: Annualized Number of pRBC Transfusions
timeFrame: From 12 months post-drug product infusion through Month 24
measure: Annualized Volume of pRBC Transfusions
timeFrame: From 12 to 24 months post-transplant
measure: Time From Drug Product Infusion to Last pRBC Transfusion
timeFrame: From start of drug product infusion up to Month 24
measure: Time From Last pRBC Transfusion to 24 Months
timeFrame: From last pRBC Transfusion up to Month 24 (actual maximum time frame of up to approximately 27 months due to visit window)
measure: Weighted Average Nadir Hemoglobin (Hb)
timeFrame: 12 months post-drug product infusion through Month 24
measure: Unsupported Total Hb Levels at Month 6, 9, 12, 18 and 24
timeFrame: At Month 6, 9, 12, 18 and 24
measure: 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
timeFrame: At Months 6, 9, 12, 18 and 24
measure: Percentage of Participants Who Have Not Received Chelation Therapy for At Least 6 Months Following Drug Product Infusion
timeFrame: From 6 to 24 months
measure: Time From Last Iron Chelation Use to Last Follow-up
timeFrame: From last Iron Chelation up to Month 24 (actual maximum time frame of up to approximately 29 months due to visit window)
measure: Number of Participants Who Used Therapeutic Phlebotomy Post Drug Product Infusion
timeFrame: From drug product infusion through Month 24
measure: Annualized Phlebotomy Therapy Usage Following Drug Product Infusion
timeFrame: From drug product infusion through Month 24
measure: Change From Baseline in Liver Iron Content by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Month 12 and 24
measure: Change From Baseline in Cardiac T2* on MRI
timeFrame: Baseline, Months 12 and 24
measure: Change From Baseline in Serum Ferritin
timeFrame: Baseline, Month 12 and 24
measure: Change From Baseline in Pediatric Quality of Life Inventory (PedsQL) Total Scores at Months 12 and 24
timeFrame: Baseline, Month 12 and 24
measure: Change From Baseline in EuroQol Quality of Life 5-Dimension Youth Scale (EQ-5D-Y) VAS Health Status at Months 12 and 24
timeFrame: Baseline, Months 12 and 24
measure: Change From Baseline in EuroQol Quality of Life 5-Dimension Adult Scale (EQ-5D-3L) VAS Heath Status Score at Months 12 and 24
timeFrame: Baseline, Months 12 and 24
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Total Score
timeFrame: Baseline, Months 12 and 24
measure: 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
timeFrame: Baseline, Months 12 and 24
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Marseille
country: France
facility: Hopital d'enfants de la Timone
city: Hannover
country: Germany
facility: Hannover Medical School
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Thessaloníki
country: Greece
facility: General Hospital of Thessaloniki 'G.Papanikolaou'
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Babino Gesu
city: London
country: United Kingdom
facility: University College London Hospital
Study officials:
affiliation: bluebird bio
name: Himal L Thakar, MD
role: STUDY_DIRECTOR
References: