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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01745120




Registration number
NCT01745120
Ethics application status
Date submitted
6/12/2012
Date registered
7/12/2012
Date last updated
8/05/2019

Titles & IDs
Public title
A Study Evaluating the Safety and Efficacy of the LentiGlobin BB305 Drug Product in ß-Thalassemia Major Participants
Scientific title
A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With ß-Thalassemia Major by Transplantation of Autologous CD34+ Cells Transduced Ex Vivo With a Lentiviral ßA-T87Q-Globin Vector (LentiGlobin® BB305 Drug Product)
Secondary ID [1] 0 0
HGB-204
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ß-thalassemia Major 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - LentiGlobin BB305 Drug Product

Experimental: LentiGlobin BB305 Drug Product -


Treatment: Other: LentiGlobin BB305 Drug Product
Transplant of autologous hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Sustained Production of >=2.0 Grams Per Deciliter (g/dL) of Hemoglobin A (HbA) Containing ßA-T87Q-globin (HbAT87Q) for the Six Months Between Month 18 and Month 24
Timepoint [1] 0 0
Month 18 to Month 24
Primary outcome [2] 0 0
Percentage of Participants Who Achieved Transfusion Independence (TI)
Timepoint [2] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [1] 0 0
Percentage of Participants Who Achieved Transfusion Independence (TI) at Month 18 and Month 24
Timepoint [1] 0 0
Month 18, Month 24
Secondary outcome [2] 0 0
Duration of Transfusion Independence (TI)
Timepoint [2] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [3] 0 0
Time From LentiGlobin BB305 Drug Product Infusion to Last pRBC Transfusion Prior to Achieving Transfusion Independence (TI)
Timepoint [3] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [4] 0 0
Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI)
Timepoint [4] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [5] 0 0
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI)
Timepoint [5] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [6] 0 0
Percentage Change From Baseline in Annualized Number of Packed Red Blood Cells (pRBC) Transfusions at Month 24
Timepoint [6] 0 0
Baseline, Month 24
Secondary outcome [7] 0 0
Percentage Change From Baseline in Average Annual Packed Red Blood Cells (pRBC) Transfusion Volume at Month 24
Timepoint [7] 0 0
Baseline, Month 24
Secondary outcome [8] 0 0
Weighted Average Nadir Hemoglobin (Hb)
Timepoint [8] 0 0
Baseline, Month 6 to Month 24
Secondary outcome [9] 0 0
Number of Participants With Successful Neutrophil Engraftment
Timepoint [9] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [10] 0 0
Time to Neutrophil Engraftment
Timepoint [10] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [11] 0 0
Number of Participants With Successful Platelet Engraftment
Timepoint [11] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [12] 0 0
Time to Platelet Engraftment
Timepoint [12] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [13] 0 0
Transplant-related Mortality
Timepoint [13] 0 0
Through 100 and 365 days post-LentiGlobin BB305 Drug Product infusion
Secondary outcome [14] 0 0
Overall Survival
Timepoint [14] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [15] 0 0
Percentage of Participants Detected With Replication-competent Lentivirus (RCL)
Timepoint [15] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [16] 0 0
Number of Participants With Integration Site Analysis (ISA) With >30% Clonal Contribution
Timepoint [16] 0 0
From time of drug product infusion up to 24 months
Secondary outcome [17] 0 0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [17] 0 0
From signing of informed consent to 24 months after the drug product infusion

Eligibility
Key inclusion criteria
Inclusion criteria:

* Participants between 12 and 35 years of age, inclusive, at the time of consent/assent, and able to provide written consent/assent, if applicable.
* Diagnosis of ß-thalassemia major and a history of at least 100 mL/kg/year of pRBCs or =8 transfusions of pRBCs per year for the prior 2 years.
* Eligible for allogeneic bone marrow transplant.
* Treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
Minimum age
12 Years
Maximum age
35 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Positive for presence of human immunodeficiency virus type 1 or 2 (HIV 1 and HIV 2).
* A white blood cell (WBC) count <3 × 10^9/L, and / or platelet count <100 × 10^9/L if not due to hypersplenism.
* Uncorrected bleeding disorder.
* Any prior or current malignancy or myeloproliferative or immunodeficiency disorder.
* Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome and familial adenomatous polyposis).
* Receipt of an allogeneic transplant.
* Advanced liver disease, including persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 × the upper limit of normal, liver biopsy demonstrating cirrhosis, extensive bridging fibrosis, or active hepatitis.
* Kidney disease with a calculated creatinine clearance <30% normal value.
* Uncontrolled seizure disorder.
* Diffusion capacity of carbon monoxide (DLco) <50% of predicted (corrected for hemoglobin).
* A cardiac T2* <10 ms by magnetic resonance imaging (MRI).
* Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion.
* Clinically significant pulmonary hypertension, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental home oxygen.
* Participation in another clinical study with an investigational drug within 30 days of Screening.
* Any prior or current malignancy or myeloproliferative disorder.
* Prior receipt of gene therapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/02/2018
Sample size
Target
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Sydney
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
Thailand
State/province [4] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
bluebird bio
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a non-randomized, open label, multi-site, single-dose, phase 1/2 study in up to 18 participants (including at least 3 adolescents between 12 and 17 years of age, inclusive) with ß-thalassemia major. The study will evaluate the safety and efficacy of autologous hematopoietic stem cell transplantation (HSCT) using LentiGlobin BB305 Drug Product \[autologous CD34+ hematopoietic stem cells transduced with LentiGlobin BB305 lentiviral vector encoding the human ßA-T87Q-globin gene\].
Trial website
https://clinicaltrials.gov/study/NCT01745120
Trial related presentations / publications
Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, Magrin E, Schiller GJ, Payen E, Semeraro M, Moshous D, Lefrere F, Puy H, Bourget P, Magnani A, Caccavelli L, Diana JS, Suarez F, Monpoux F, Brousse V, Poirot C, Brouzes C, Meritet JF, Pondarre C, Beuzard Y, Chretien S, Lefebvre T, Teachey DT, Anurathapan U, Ho PJ, von Kalle C, Kletzel M, Vichinsky E, Soni S, Veres G, Negre O, Ross RW, Davidson D, Petrusich A, Sandler L, Asmal M, Hermine O, De Montalembert M, Hacein-Bey-Abina S, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia. N Engl J Med. 2018 Apr 19;378(16):1479-1493. doi: 10.1056/NEJMoa1705342.
Public notes

Contacts
Principal investigator
Name 0 0
Mohammed Asmal, MD
Address 0 0
bluebird bio
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01745120