Beta-Thalassemia MajorPhase 1/2NCT02151526

A Study Evaluating the Safety and Efficacy of LentiGlobin BB305 Drug Product in β-Thalassemia Major (Also Referred to as Transfusion-dependent β-Thalassemia [TDT]) and Sickle Cell Disease

A Phase 1/2 study testing LentiGlobin BB305 Drug Product in people with Beta-Thalassemia Major and Sickle Cell Disease, run by Genetix Biotherapeutics Inc. at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

This is a Phase 1/2, open label, safety, and efficacy study of the administration of LentiGlobin BB305 Drug Product to participants with either transfusion dependent beta-thalassemia (TDT) or sickle cell disease (SCD). Read more about this study

Who is it for?: Ages 5 to 35 years
Conditions the study is for: Beta-Thalassemia Major, Sickle Cell Disease
What is being tested?: LentiGlobin BB305 Drug Product
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteFrance
Study dates: 7 Jun 2013to 26 Feb 2019
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 5 to 35 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Be between 5 and 35 years of age, inclusive.
Have severe SCD or transfusion dependent beta-thalassemia major, regardless of the genotype with the diagnosis confirmed by Hb studies. Transfusion dependence is defined as requiring at least 100 mL/kg/year of packed red blood cells (pRBCs).
Be eligible for allogeneic hematopoietic stem cell transplant (HSCT) based on institutional medical guidelines, but without a matched related donor.
Be willing and able, in the Investigator's opinion, to comply with the study procedures outlined in the study protocol.
Have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.
Participants with severe SCD also must:

Show all 16Show fewer

Have failed to achieve adequate clinical benefit following hydroxyurea treatment with sufficient dosage, for at least 4 months unless this treatment was not indicated or not well tolerated.
Have 1 or more of the following poor prognostic risk factors:
Recurrent vaso occlusive crises (at least 2 episodes in the preceding year or in the year prior to start of a regular transfusion program).
Presence of any significant cerebral abnormality on magnetic resonance imaging (MRI) (such as stenosis or occlusions).
Stroke without any severe cognitive disability.
Osteonecrosis of 2 or more joints.
Anti-erythrocyte alloimmunization (>2 antibodies).
Presence of sickle cell cardiomyopathy documented by Doppler echocardiography.
Acute chest syndrome (at least 2 episodes) defined by an acute event with pneumonia-like symptoms (e.g., cough, fever [>38.5°C], acute dyspnea, expectoration, chest pain, findings upon lung auscultation, tachypnea, or wheezing) and the presence of a new pulmonary infiltrate. Participants with a chronic oxygen saturation <90% (excluding periods of SCD crisis) or carbon monoxide diffusing capacity (DLco) less than 60% in the absence of an infection should not be included in the study.
Participants with severe SCD and cerebral vasculopathy (defined by overt stroke; abnormal transcranial Doppler [> 170 cm/sec]; or occlusion or stenosis in the polygon of Willis; or presence of Moyamoya disease) may be enrolled only with approval by the Comite de Surveillance after review of safety and efficacy data from >or= 2 SCD participants without cerebral vasculopathy treated with LentiGlobin BB305 Drug Product

Who cannot join

Availability of a willing 10 /10 matched human leukocyte antigen (HLA) identical sibling hematopoietic cell donor, unless recommendation for enrollment is provided by the Comite de Surveillance following a review of the case.
Clinically significant, active bacterial, viral, fungal, or parasitic infection.
Contraindication to anesthesia for bone marrow harvesting.
Any prior or current malignancy, myeloproliferative or immunodeficiency disorder.
A white blood cell (WBC) count <3×10^9/L and/or platelet count <120×10^9/L.
History of major organ damage including:

Show all 14Show fewer

Liver disease, with transaminase levels >3× upper limit of normal.
This observation will not be exclusionary if a liver biopsy shows no evidence of extensive bridging fibrosis, cirrhosis, or acute hepatitis.
Histopathological evidence of extensive bridging fibrosis, cirrhosis, or acute hepatitis on liver biopsy.
Heart disease, with a left ventricular ejection fraction <25%.
Kidney disease with a calculated creatinine clearance <30% normal value.
Severe iron overload, which in the opinion of the physician is grounds for exclusion.
A cardiac T2* <10 ms by magnetic resonance imaging (MRI).
Evidence of clinically significant pulmonary hypertension requiring medical intervention.

Trial locations and contacts

1 site in 1 country.

France1 site

Study site
Paris

Other trials in France

About this study

Official title: A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the β-Hemoglobinopathies (Sickle Cell Anemia and β-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral β-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product)

Conditions: Beta-Thalassemia Major, Sickle Cell Disease
Being tested: LentiGlobin BB305 Drug Product
Medical subject headings: beta-Thalassemia, Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LentiGlobin BB305 Drug ProductDrug
LentiGlobin BB305 Drug Product was administered by intravenous (IV) infusion.

Study groups in NCT02151526
Study group	Role	What they receive
LentiGlobin BB305 Drug Product	Experimental	Following myeloablative conditioning with IV busulfan for 4 consecutive days (dose may be adjusted as per protocol) and subsequent daily monitoring of busulfan levels for confirmation of adequate washout, a single dose cluster of differentiation (CD) 34+ cells/kg LentiGlobin BB305 Drug Product was administered to participants by IV infusion. Receives: Drug: LentiGlobin BB305 Drug Product

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Treated Participants With Successful Neutrophil and Platelet Engraftment
Neutrophil engraftment was defined as the first of absolute neutrophil count (ANC) > or = 0.5 × 10^9/ liter (L) for 3 consecutive days (or 3 consecutive measurements done on separate days), after a post-transplant value less than (<) 0.5 × 10^9/L. Platelet engraftment was defined as the first of 3 consecutive platelet values > or =20 × 10^9/L for participants with TDT and values > or =50 × 10^9/L for participants with SCD obtained on different days with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Measured: From time of drug product infusion through Month 24
Time to Successful Neutrophil and Platelet Engraftment
Neutrophil engraftment was defined as the first of ANC > or = 0.5 × 10^9/ liter (L) for 3 consecutive days (or 3 consecutive measurements done on separate days), after a post-transplant value < 0.5 × 10^9/L). Platelet engraftment was defined as the first of 3 consecutive platelet values > or =20 × 10^9/L for participants with TDT and values > or =50 × 10^9/L for participants with SCD obtained on different days with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Measured: From time of drug product infusion through Month 24
Incidence of Transplant Related Mortality
This was the safety outcome measure related to mortality. Transplant related mortality was defined as any death occurring in the study post drug product infusion deemed related to the transplant by the investigator.
Measured: From screening through 365 days post-transplant
Number of Participants With Overall Survival (OS) Events
Overall survival was defined as time from date of LentiGlobin BB305 Drug Product infusion (Day 1) to date of death. Overall survival was censored at the date of last visit if the participant was still alive. Number of participants with OS events were reported.
Measured: From time of drug product infusion through Month 24
Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)
Blood samples were analyzed for detection of RCL using RCL co-culture assay.
Measured: From time of drug product infusion through Month 24
Number of Treated Participants With Greater Than (>) 30 Percent (%) Contribution of an Individual Clone As Per Integration Site Analysis (ISA)
Clonal dominance was defined as an ISA result greater than (>) 90% of the total insertion sites (IS) at any time and a vector copy number (VCN) > or =0.3, or an initial ISA result of > 30% of the total IS with a VCN > or =0.3 followed by a result > 30% and less than or equal to (< or =) 90% at first repeat and a result > 50% at second repeat.
Measured: From time of drug product infusion through Month 24
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE may include a change in physical signs, symptoms, and/or clinically significant laboratory change occurring in any phase of a clinical study. This definition includes inter-current illnesses or injuries, and exacerbation of pre-existing conditions. An SAE was any AE, occurring at any dose and regardless of causality, that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or was considered an important medical event that may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed previously. The number of participants with AEs and SAEs were evaluated.
Measured: From date of Informed Consent signing up to Month 24

Secondary outcomes (11)

Percentage of Treated Participants With Transfusion-Dependent β-Thalassemia (TDT) Who Achieved Transfusion Independence (TI)
TI was defined as a weighted average hemoglobin (Hb) > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days.
Measured: From time of drug product infusion through Month 24
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
TI was defined as a weighted average hemoglobin (Hb) > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days.
Measured: From time of drug product infusion through Month 24
Duration of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
TI was defined as a weighted average Hb > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days. To meet the initial TI criteria, the weighted Hb must be > or =9 g/dL at the end of the 12-month period, to remain in the TI state beyond the 12-month period, the treated participant needs to maintain a weighted Hb of > or =9 g/dL from that point forward, without receiving a pRBC transfusion. This outcome measure reports the duration of TI and was evaluated in the TDT Transplant Population (TP) that reached TI.
Measured: From time of drug product infusion through Month 24
Time From LentiGlobin BB305 Drug Product Infusion to Last Packed Red Blood Cells (pRBC) Transfusion Prior to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
TI was defined as a weighted average Hb > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days. To meet the initial TI criteria, the weighted Hb must be > or =9 g/dL at the end of the 12-month period, to remain in the TI state beyond the 12-month period, the treated participant needs to maintain a weighted Hb of > or =9 g/dL from that point forward, without receiving a pRBC transfusion. This endpoint reports the time from infusion to the last pRBC transfusion prior to achieving TI.
Measured: From time of drug product infusion through Month 24
Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
TI was defined as a weighted average Hb > or =9 grams per deciliter (g/dL) without any pRBC transfusions for a continuous period of > or =12 months at any time during the study after drug product infusion, where calculation of time period of TI starts when participants achieve a Hb > or =9 g/dL with no transfusions in the preceding 60 days. To meet the initial TI criteria, the weighted Hb must be > or =9 g/dL at the end of the 12-month period, to remain in the TI state beyond the 12-month period, the treated participant needs to maintain a weighted Hb of > or =9 g/dL from that point forward, without receiving a pRBC transfusion. This outcome measure reports the time from infusion to achievement of TI.
Measured: From time of drug product infusion through Month 24
Weighted Average Nadir Hemoglobin (Hb) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
Weighted average Hb nadir was defined as an average area under the curve where the Hb closest but within 3 days prior to a transfusion was used as the Hb nadir. Hb values on the day of the transfusion were considered for nadir calculations.
Measured: From 6 months post-drug product infusion through Month 24
Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume
Percent change from baseline in the average annual transfusion volume from 6 months post-drug product infusion through last visit were reported.
Measured: Baseline, From 6 months post-drug product infusion through Month 24
Percentage Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions
Percentage change from baseline in annualized number of pRBC transfusions from 6 months post-drug product infusion through last visit were reported.
Measured: Baseline, From 6 months post-drug product infusion through Month 24
Number of Participants With Vaso-Occlusive Crisis (VOC) and/or Acute Chest Syndrome (ACS) Events Post Drug Product Infusion in Sickle Cell Disease Participants
Number of VOCs, ACS, and vaso-occlusive events (VOEs; which included both VOC and ACS) through 24 months after drug product infusion.
Measured: From time of drug product infusion through Month 24
Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood
Therapeutic globin expression was measured by HbA^T87Q in peripheral blood and the ratio of alpha(α)- globin to all beta (β)-like-globins. The relative amount of each globin produced by a participant (including βA^A-T87Q globin) was determined in peripheral blood throughout the study.
Measured: From time of drug product infusion through Month 24
Vector Copy Number (VCN) in Peripheral Blood
LentiGlobin BB305 lentiviral vector (LVV) transduction efficiency was measured by VCN. The presence of vector sequences in the genomic DNA of cells is detected using quantitative polymerase chain reaction (qPCR), and results were expressed as VCN.
Measured: From time of drug product infusion through Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Jun 201326 Feb 2019

First posted30 May 2014 (estimated)
Study start7 Jun 2013
Primary completion26 Feb 2019
Study completion26 Feb 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Beta-Thalassemia MajorStudies of the same condition, open and under way.
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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02151526
Sponsor's protocol ID: HGB-205
Other IDs: 2012-000695-42
Status last verified: Apr 2022
First submitted: 14 May 2014
Last updated: 26 Apr 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Treluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poiree M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M. Long-term outcomes of lentiviral gene therapy for the beta-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88. doi: 10.1038/s41591-021-01650-w. Epub 2022 Jan 24.
PubMed 35075288
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.
PubMed 29669226
Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, Caccavelli L, Neven B, Bourget P, El Nemer W, Bartolucci P, Weber L, Puy H, Meritet JF, Grevent D, Beuzard Y, Chretien S, Lefebvre T, Ross RW, Negre O, Veres G, Sandler L, Soni S, de Montalembert M, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 2017 Mar 2;376(9):848-855. doi: 10.1056/NEJMoa1609677.
PubMed 28249145

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Transfusion-dependent Beta-Thalassemia
RecruitingObservational study
Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy
Transfusion-dependent Beta-Thalassemia, Gene Therapy
Not yet recruiting
Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
Beta-Thalassemia
RecruitingPhase 1/2
β-Thalassemia Treatment With KL003 Cell Injection
Transfusion-dependent Beta-Thalassemia
Active, not recruitingPhase 3
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

All Beta-Thalassemia Major trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1/2 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy of the β-Hemoglobinopathies (Sickle Cell Anemia and β-Thalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Transduced Ex Vivo With a Lentiviral β-A-T87Q Globin Vector (LentiGlobin BB305 Drug Product)
ClinicalTrials.gov ID: NCT02151526
Acronym / sponsor ID: HGB-205
Conditions: Beta-Thalassemia Major, Sickle Cell Disease
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: Genetix Biotherapeutics Inc.Industry (pharma, biotech, devices)
Study start: 7 Jun 2013 (actual)
Primary completion: 26 Feb 2019 (actual)
Study completion: 26 Feb 2019 (actual)
First posted: 30 May 2014 (estimated)
Results: Posted 10 Mar 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
LentiGlobin BB305 Drug Product	Experimental	Drug: LentiGlobin BB305 Drug ProductFollowing myeloablative conditioning with IV busulfan for 4 consecutive days (dose may be adjusted as per protocol) and subsequent daily monitoring of busulfan levels for confirmation of adequate washout, a single dose cluster of differentiation (CD) 34+ cells/kg LentiGlobin BB305 Drug Product was administered to participants by IV infusion.

Who may qualify

Ages: 5 to 35 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (16 listed)

Be between 5 and 35 years of age, inclusive.
Have severe SCD or transfusion dependent beta-thalassemia major, regardless of the genotype with the diagnosis confirmed by Hb studies. Transfusion dependence is defined as requiring at least 100 mL/kg/year of packed red blood cells (pRBCs).
Be eligible for allogeneic hematopoietic stem cell transplant (HSCT) based on institutional medical guidelines, but without a matched related donor.
Be willing and able, in the Investigator's opinion, to comply with the study procedures outlined in the study protocol.
Have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

Key exclusion criteria (14 listed)

Availability of a willing 10 /10 matched human leukocyte antigen (HLA) identical sibling hematopoietic cell donor, unless recommendation for enrollment is provided by the Comite de Surveillance following a review of the case.
Clinically significant, active bacterial, viral, fungal, or parasitic infection.
Contraindication to anesthesia for bone marrow harvesting.
Any prior or current malignancy, myeloproliferative or immunodeficiency disorder.
A white blood cell (WBC) count <3×10^9/L and/or platelet count <120×10^9/L.

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
LentiGlobin BB305 Drug ProductLentiGlobin BB305 Drug Product was administered by intravenous (IV) infusion.	Drug	LentiGlobin BB305 Drug Product

Primary outcome

Number of Treated Participants With Successful Neutrophil and Platelet Engraftment
Time frame: From time of drug product infusion through Month 24
Neutrophil engraftment was defined as the first of absolute neutrophil count (ANC) > or = 0.5 × 10^9/ liter (L) for 3 consecutive days (or 3 consecutive measurements done on separate days), after a post-transplant value less than (<) 0.5 × 10^9/L. Platelet engraftment was defined as the first of 3 consecutive platelet values > or =20 × 10^9/L for participants with TDT and values > or =50 × 10^9/L for participants with SCD obtained on different days with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Time to Successful Neutrophil and Platelet Engraftment
Time frame: From time of drug product infusion through Month 24
Neutrophil engraftment was defined as the first of ANC > or = 0.5 × 10^9/ liter (L) for 3 consecutive days (or 3 consecutive measurements done on separate days), after a post-transplant value < 0.5 × 10^9/L). Platelet engraftment was defined as the first of 3 consecutive platelet values > or =20 × 10^9/L for participants with TDT and values > or =50 × 10^9/L for participants with SCD obtained on different days with no platelet transfusions administered for 7 days immediately preceding and during the evaluation period. The day of engraftment is the first day of the 3 consecutive platelet measurements.
Incidence of Transplant Related Mortality
Time frame: From screening through 365 days post-transplant
This was the safety outcome measure related to mortality. Transplant related mortality was defined as any death occurring in the study post drug product infusion deemed related to the transplant by the investigator.
Number of Participants With Overall Survival (OS) Events
Time frame: From time of drug product infusion through Month 24
Overall survival was defined as time from date of LentiGlobin BB305 Drug Product infusion (Day 1) to date of death. Overall survival was censored at the date of last visit if the participant was still alive. Number of participants with OS events were reported.
Percentage of Participants With Vector-Derived Replication-Competent Lentivirus (RCL)
Time frame: From time of drug product infusion through Month 24
Blood samples were analyzed for detection of RCL using RCL co-culture assay.
Number of Treated Participants With Greater Than (>) 30 Percent (%) Contribution of an Individual Clone As Per Integration Site Analysis (ISA)
Time frame: From time of drug product infusion through Month 24
Clonal dominance was defined as an ISA result greater than (>) 90% of the total insertion sites (IS) at any time and a vector copy number (VCN) > or =0.3, or an initial ISA result of > 30% of the total IS with a VCN > or =0.3 followed by a result > 30% and less than or equal to (< or =) 90% at first repeat and a result > 50% at second repeat.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From date of Informed Consent signing up to Month 24
An AE was any untoward medical occurrence associated with the use of a drug in participants, whether or not considered drug related. An AE may include a change in physical signs, symptoms, and/or clinically significant laboratory change occurring in any phase of a clinical study. This definition includes inter-current illnesses or injuries, and exacerbation of pre-existing conditions. An SAE was any AE, occurring at any dose and regardless of causality, that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or was considered an important medical event that may jeopardize the participant and may require medical or surgical intervention to prevent an outcome listed previously. The number of participants with AEs and SAEs were evaluated.

11 secondary outcomes

Percentage of Treated Participants With Transfusion-Dependent β-Thalassemia (TDT) Who Achieved Transfusion Independence (TI)
Time frame: From time of drug product infusion through Month 24
Weighted Average Hemoglobin (Hb) During Period of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
Time frame: From time of drug product infusion through Month 24
Duration of Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
Time frame: From time of drug product infusion through Month 24
Time From LentiGlobin BB305 Drug Product Infusion to Last Packed Red Blood Cells (pRBC) Transfusion Prior to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
Time frame: From time of drug product infusion through Month 24
Time From LentiGlobin BB305 Drug Product Infusion to Achieving Transfusion Independence (TI) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
Time frame: From time of drug product infusion through Month 24
Weighted Average Nadir Hemoglobin (Hb) in Participants With Transfusion-Dependent β-Thalassemia (TDT)
Time frame: From 6 months post-drug product infusion through Month 24
Percentage Change From Baseline in Annualized Packed Red Blood Cell (pRBC) Transfusion Volume
Time frame: Baseline, From 6 months post-drug product infusion through Month 24
Percentage Change From Baseline in Annualized Number of Packed Red Blood Cell (pRBC) Transfusions
Time frame: Baseline, From 6 months post-drug product infusion through Month 24
Number of Participants With Vaso-Occlusive Crisis (VOC) and/or Acute Chest Syndrome (ACS) Events Post Drug Product Infusion in Sickle Cell Disease Participants
Time frame: From time of drug product infusion through Month 24
Therapeutic Globin Expression Measured by Hb Containing β^A -T87Q Globin (HbA^T87Q) in Peripheral Blood
Time frame: From time of drug product infusion through Month 24
Vector Copy Number (VCN) in Peripheral Blood
Time frame: From time of drug product infusion through Month 24

Results and safety

Results posted to the registry on 10 Mar 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LentiGlobin BB305 Drug Product for SCD	3	3
LentiGlobin BB305 Drug Product for TDT	4	4

Primary outcome: Number of Treated Participants With Successful Neutrophil and Platelet Engraftment

Time frame: From time of drug product infusion through Month 24. Count of participants. Unit: Participants

Measure	LentiGlobin BB305 Drug Product for SCD n = 3	LentiGlobin BB305 Drug Product for TDT n = 4
Participants with Neutrophil Engraftment	3	4
Participants with Platelet Engraftment	3	4

Population analysed: Transplant Population (TP) included all participants in the Intent to treat population who underwent LentiGlobin BB305 Drug Product infusion.

Primary outcome: Time to Successful Neutrophil and Platelet Engraftment

Time frame: From time of drug product infusion through Month 24. Median (Full Range). Unit: Days

Measure	LentiGlobin BB305 Drug Product for SCD n = 3	LentiGlobin BB305 Drug Product for TDT n = 4
Time to Neutrophil Engraftment	32 (27 to 38)	16.5 (14 to 29)
Time to Platelet Engraftment	51 (39 to 92)	23 (20 to 26)

Population analysed: This outcome measure was evaluated in the Transplant Population (TP).

Primary outcome: Incidence of Transplant Related Mortality

Time frame: From screening through 365 days post-transplant. Number. Unit: Number of deaths reported

Measure	LentiGlobin BB305 Drug Product for SCD n = 3	LentiGlobin BB305 Drug Product for TDT n = 4
Value	0	0

Population analysed: This outcome measure was evaluated in the Transplant Population (TP).

Primary outcome: Number of Participants With Overall Survival (OS) Events

Time frame: From time of drug product infusion through Month 24. Count of participants. Unit: Participants

Measure	LentiGlobin BB305 Drug Product for SCD n = 3	LentiGlobin BB305 Drug Product for TDT n = 4
Censored Participants	3	4
Participants reported OS events	0	0

Population analysed: Intent to Treat (ITT) population consisted of all participants who initiated any study procedures, beginning with mobilization (by Granulocyte colony stimulating factor \[G-CSF\] with or without plerixafor), or bone marrow harvest.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: From date of Informed Consent signing up to Month 24. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LentiGlobin BB305 Drug Product for SCD	3 of 3 (100%)	3 of 3 (100%)	0 of 3
LentiGlobin BB305 Drug Product for TDT	3 of 4 (75%)	4 of 4 (100%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35075288Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, Gabrion A, Roudaut C, Marouene J, Lefrere F, Diana JS, Denis A, Neven B, Funck-Brentano I, Negre O, Renolleau S, Brousse V, Kiger L, Touzot F, Poirot C, Bourget P, El Nemer W, Blanche S, Treluyer JM, Asmal M, Walls C, Beuzard Y, Schmidt M, Hacein-Bey-Abina S, Asnafi V, Guichard I, Poiree M, Monpoux F, Touraine P, Brouzes C, de Montalembert M, Payen E, Six E, Ribeil JA, Miccio A, Bartolucci P, Leboulch P, Cavazzana M. Long-term outcomes of lentiviral gene therapy for the beta-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88. doi: 10.1038/s41591-021-01650-w. Epub 2022 Jan 24.
Derived from this study: PubMed 29669226Thompson 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.
Derived from this study: PubMed 28249145Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, Caccavelli L, Neven B, Bourget P, El Nemer W, Bartolucci P, Weber L, Puy H, Meritet JF, Grevent D, Beuzard Y, Chretien S, Lefebvre T, Ross RW, Negre O, Veres G, Sandler L, Soni S, de Montalembert M, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 2017 Mar 2;376(9):848-855. doi: 10.1056/NEJMoa1609677.

Related trials for Beta-Thalassemia Major

Active, not recruiting
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Transfusion-dependent Beta-Thalassemia
RecruitingObservational study
Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy
Transfusion-dependent Beta-Thalassemia, Gene Therapy
Not yet recruiting
Gene Therapy of Beta Thalassemia Using a Self-inactivating Lentiviral Vector
Beta-Thalassemia
RecruitingPhase 1/2
β-Thalassemia Treatment With KL003 Cell Injection
Transfusion-dependent Beta-Thalassemia
Active, not recruitingPhase 3
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.

Jean-Antoine Ribeil, MD study director

bluebird bio, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LentiGlobin BB305 Drug Product in people with Beta-Thalassemia Major and Sickle Cell Disease, run by Genetix Biotherapeutics Inc. at 1 site in France.

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 16 inclusion and 14 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: finished, as of the sponsor's last update on 26 Apr 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 France. 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.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Treated Participants With Successful Neutrophil and Platelet Engraftment (time frame: From time of drug product infusion through Month 24). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02151526, which also lists 3 linked publications.

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 26 Apr 2022.