Clinical trial NCT05015920: 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
Overall status: COMPLETED
Phase: NA
Conditions: Hematologic Diseases
Keywords: TDT
β-thalassemia major
Lead sponsor: Shanghai BDgene Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
First posted: 2021-08-23
Enrollment: 2
Sex: ALL
Minimum age (years): 5
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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:

1. Availability of a willing matched HLA-identical sibling hematopoietic cell donor.
2. Positive for presence of human immunodeficiency virus, human T-lymphotropic virus, vesicular stomatitis virus G antibody.
3. Clinically significant, active bacterial, viral, fungal, or parasitic infection.
4. A white blood cell (WBC) count\<3x109/L and/or platelet count\<120x109/L
5. Receipt of an allogeneic transplant.
6. Receipt of erythropoietin within 3 months before HSCT harvest.
7. Contraindication to anesthesia for bone marrow harvesting.
8. Any of prior or current malignancy, myeloproliferative or immunodeficiency disorder.
9. Active relapsing malaria
10. Immediate family member with a known or suspected Familial Cancer Syndrome.
11. Diagnosis of significant psychiatric disorder of the subject that could seriously impede the ability to participate in the study.
12. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception for fertile subjects.
13. Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician.
14. 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.
15. Participation in another clinical study with an investigational drug within 30 days of screening.
16. Hydroxyurea therapy within 3 months before hematopoietic stem cell collection.
17. 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.
18. Subjects who have the desire to become a parent within the 27-month study period.
19. Prior receipt of gene therapy.

Primary outcomes:
measure: Evaluate the success and kinetics of HSC engraftment.
timeFrame: At multiple timepoints after infusion for 24 months.
measure: Incidence of transplant-related mortality through 100 days post-transplant.
timeFrame: Up to 100 days post-HSCT.
measure: Overall survival of maintenance phase.
timeFrame: Up to 24 months post-HSCT.
measure: Post-transplant blood samples for replication competent lentivirus (RCL) testing.
timeFrame: At multiple timepoints after infusion for 24 months.
measure: Assessment of Clonal dominance or leukemia/lymphoma and other malignancies.
timeFrame: At multiple timepoints after infusion for 24 months.
measure: Incidence of treatment- related adverse events.
timeFrame: Up to 24 months after BD211 drug product infusion.
Secondary outcomes:
measure: Quantify gene transfer efficiency and expression of BD211 drug product.
timeFrame: Up to 24 months after engraftment.
measure: Quantify the hematopoietic chimerism resulting from treatment with BD211 drug product.
timeFrame: Up to 24 months after engraftment.
measure: HbAT87Q in peripheral blood
timeFrame: Up to 24 months after engraftment.
measure: Reduction of RBC transfusion requirements from baseline
timeFrame: Up to 24 months after engraftment.
measure: Duration of transfusion independence (months).
timeFrame: Up to 24 months after engraftment.
measure: Weighted average Hemoglobin
timeFrame: Up to 24 months after engraftment.
measure: Changes of liver iron burden from baseline
timeFrame: Up to 24 months after engraftment.
measure: Changes of cardiac iron burden from baseline
timeFrame: Up to 24 months after engraftment.
Other outcomes:
Locations:
city: Kunming
country: China
facility: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
state: Yunnan
Study officials:
affiliation: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: Sanbin Wang, Dr.
role: STUDY_CHAIR
References: