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A Study Evaluating the Safety and Efficacy of the BD211 Drug Product in β-Thalassemia Major Participants

Primary Purpose

Hematologic Diseases

Status

Recruiting

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

BD211 Drug Product

About this trial

This is an interventional prevention trial for Hematologic Diseases focused on measuring TDT, β-thalassemia major

Eligibility Criteria

5 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1.5 to 35 years of age.

2.Be eligible for allogeneic HSCT based on institutional medical guideline, but without a matched related donor.

3.Transfusion-dependent β-Thalassemia Major, regardless of the genotype, with the diagnosis confirmed by Hb studies. Subjects must be stable and maintained on an appropriate iron chelation regimen. Transfusion dependence is defined as requiring at least 100 mL/kg/year of packed red blood cells(pRBCs).

4.Have been treated and followed for at least the past 2 years in a specialized center that maintained detailed medical records, including transfusion history.

5.Be willing and able, in the Investigator's opinion, to comply with the study procedures outlined in the study protocol. If a pediatric subject, the subject's parent/legal guardian also must be willing and able to comply with the study procedures outlined in the study protocol.

Exclusion Criteria:

Availability of a willing matched HLA-identical sibling hematopoietic cell donor.
Positive for presence of human immunodeficiency virus, human T-lymphotropic virus, vesicular stomatitis virus G antibody.
Clinically significant, active bacterial, viral, fungal, or parasitic infection.
A white blood cell (WBC) count<3x109/L and/or platelet count<120x109/L
Receipt of an allogeneic transplant.
Receipt of erythropoietin within 3 months before HSCT harvest.
Contraindication to anesthesia for bone marrow harvesting.
Any of prior or current malignancy, myeloproliferative or immunodeficiency disorder.
Active relapsing malaria
Immediate family member with a known or suspected Familial Cancer Syndrome.
Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study.
Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects.
Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician.
History of major organ damage.including Liver, Heart, Kidney disease, pulmonary hypertension ,severe iron overload, which in the opinion of the physician is grounds for exclusion.
Participation in another clinical study with an investigational drug within 30 days of screening.
Hydroxyurea therapy within 3 months before hematopoietic stem cell collection.
An assessment by the Investigator that the subject or parents of the subject will not comply with the study procedures outlined in the study protocol.
Subjects who have the desire to become a parent within the 27-month study period.
Prior receipt of gene therapy.

Sites / Locations

920th Hospital of Joint Logistics Support Force of People's Liberation Army of ChinaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mobilization,harvest,transduction,conditioning,treatment,engraftment

Arm Description

Subjects will participate in this study for a total of approximately 27 months, consisting of an up to 3 months pre-transplant period(consisting of a screening period followed by autologous cell harvest, followed by a waiting period during which the harvested cells are transduced and undergo release testing, followed by treatment with busulfan IV, and a single infusion of BD211 Drug Product) and a 24-month post-transplant evaluation period. Following completion of this study, all subjects will be asked to provided consent to participate in a follow-up study for another 13 years, which will focus on long-term safety, with an emphasis on integration site analysis, and long-term efficacy.

Outcomes

Primary Outcome Measures

Evaluate the success and kinetics of HSC engraftment.

Three consecutive absolute neutrophil counts≥500 cells/uL, three consecutive platelet values ≥20 e9/L, measure blood samples monthly after BD211 drug product infusion.

Incidence of transplant-related mortality through 100 days post-transplant.

Overall survival of maintenance phase.

Post-transplant blood samples for replication competent lentivirus (RCL) testing.

The testing of any subject positivity will be considered an SAE and suspend the inclusion of new subjects.

Assessment of Clonal dominance or leukemia/lymphoma and other malignancies.

Using peripheral blood of subjects for integration site analysis via LAM-PCR & deep sequencing.

Incidence of treatment- related adverse events.

According to the requirements of the National Cancer Institute Common Terminology Standards for Adverse Events (NCI CTCAE) version 5.0, monitor laboratory parameters and the frequency and severity of clinical AEs.

Secondary Outcome Measures

Quantify gene transfer efficiency and expression of BD211 drug product.

Expression of βA-T87Q-globin chain in whole blood by assessing the ratio of βA-T87Q-globin to α-globin, as well as βA-T87Q-globin fractions in all β-chains over time by HPLC.

Quantify the hematopoietic chimerism resulting from treatment with BD211 drug product.

Measuring lentiviral vector copy number per diploid genome(c/dg) for evaluation.

Measure the effects of transplantation with BD211 on the expression of disease-specific biological parameters and clinical events, including amounts of HbAT87Q in peripheral blood in grams per deciliter (g/dL).

Reduction from baseline of RBC transfusion requirements (mL/kg) per month and year post-transplant.

Duration of transfusion independence (months).

Weighted average Hemoglobin during transfusion independence in grams per deciliter (g/dL).

Changes from baseline in iron burden by assessing liver iron content (mg Fe/g dry weight).

Changes from baseline in iron burden by assessing cardiac iron content using magnetic resonance imaging (MRI) T2* value (milliseconds, ms).

Full Information

NCT ID

NCT05015920

First Posted

June 7, 2021

Last Updated

October 24, 2022

Sponsor

Shanghai BDgene Co., Ltd.

Collaborators

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

1. Study Identification

Unique Protocol Identification Number

NCT05015920

Brief Title

A Study Evaluating the Safety and Efficacy of the BD211 Drug Product in β-Thalassemia Major Participants

Official Title

A Phase 1 Open Label Study Evaluating the Safety and Efficacy of Gene Therapy in Subjects With β-Thalassemia Major by Transplantation of Autologous CD34+Stem Cells Transduced With a Lentiviral Vector Encoding βA-T87Q-Globin

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 1, 2021 (Actual)

Primary Completion Date

February 23, 2024 (Anticipated)

Study Completion Date

February 23, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai BDgene Co., Ltd.

Collaborators

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a Phase 1,open label,safety,and efficacy study in subjects with non-β0/β0 TDT β-thalassemia Major by transplanting BD211 drug product which is for autologous use only,via a single IV administration.

Detailed Description

After collection of mobilised peripheral blood samples, the patient's autologous cells,enriched for CD34+ HSCs, undergo ex vivo transduction with lentiviral vector encoding βA-T87Q-globin to BD211 finished product,which is then infused intravenously into the patient after myeloablative busulfan conditioning to prepare bone marrow "niches" for engraftment of the HSCs. After discharge, subjects will be followed monthly, at a minimum, for 6 months and thereafter every 3 months for the remainder of the 24 months post-transplant. Evaluation will include Routine and special biological testing at regular intervals, collection of AEs and concomitant medications, and evaluation of disease specific biological and clinical parameters. Subjects will then be enrolled in a long-term follow-up protocol with annual evaluations for an additional 13 years post-transplant. The long-term follow-up study will focus on long-term safety, with an emphasis on integration site analysis, and long-term efficacy. This study will end when the last subject completes the Month 24 visit or discontinues from the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Diseases

Keywords

TDT, β-thalassemia major

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Mobilization,harvest,transduction,conditioning,treatment,engraftment

Arm Type

Experimental

Arm Description

Intervention Type

Genetic

Intervention Name(s)

BD211 Drug Product

Intervention Description

Transplantation of Autologous CD34+Stem Cells Transduced to BD211 finished Product with a Lentiviral Vector coding βA-T87Q-Globin.

Primary Outcome Measure Information:

Title

Evaluate the success and kinetics of HSC engraftment.

Description

Three consecutive absolute neutrophil counts≥500 cells/uL, three consecutive platelet values ≥20 e9/L, measure blood samples monthly after BD211 drug product infusion.

Time Frame

At multiple timepoints after infusion for 24 months.

Title

Incidence of transplant-related mortality through 100 days post-transplant.

Time Frame

Up to 100 days post-HSCT.

Title

Overall survival of maintenance phase.

Time Frame

Up to 24 months post-HSCT.

Title

Post-transplant blood samples for replication competent lentivirus (RCL) testing.

Description

The testing of any subject positivity will be considered an SAE and suspend the inclusion of new subjects.

Time Frame

At multiple timepoints after infusion for 24 months.

Title

Assessment of Clonal dominance or leukemia/lymphoma and other malignancies.

Description

Using peripheral blood of subjects for integration site analysis via LAM-PCR & deep sequencing.

Time Frame

At multiple timepoints after infusion for 24 months.

Title

Incidence of treatment- related adverse events.

Description

Time Frame

Up to 24 months after BD211 drug product infusion.

Secondary Outcome Measure Information:

Title

Quantify gene transfer efficiency and expression of BD211 drug product.

Description

Expression of βA-T87Q-globin chain in whole blood by assessing the ratio of βA-T87Q-globin to α-globin, as well as βA-T87Q-globin fractions in all β-chains over time by HPLC.

Time Frame