Clinical trial NCT05577312: Safety and Efficacy Evaluation of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia
Official title: A Phase 1/2 Clinical Study to Evaluate the Safety and Efficacy of Single Dose Intravenous Infusion of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Beta-Thalassemia
Keywords: Transfusion-Dependent β-Thalassemia
Lead sponsor: Bioray Laboratories
Sponsor class: INDUSTRY
Collaborators: name: First Affiliated Hospital of Guangxi Medical University
name: Xiangya Hospital of Central South University
name: Chinese Academy of Medical Sciences
name: Nanfang Hospital, Southern Medical University
First posted: 2022-10-13
Enrollment: 9
Sex: ALL
Minimum age (years): 3
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 non-randomized, open label, multi-site, single-dose, phase 1/2 study in subjects with Transfusion-Dependent β-Thalassemia (TDT). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (BRL-101)

Detailed description: This clinical trial is a multi-center, single-arm, single-dose, open-label study without dose escalation. The proposed dose is ≥ 3 × 106 CD34 + cells/kg administered as a single intravenous infusion. The primary objective of Phase 1 is to explore the safety of the study drug in different age groups. For subjects of each age group, myeloablative conditioning and dosing of the remaining subjects was initiated only after completion of dosing and safety observations and assessments in sentinel subjects. The Phase 2 primary objective was to determine the effectiveness of BRL-101 administered intravenously to patients with TDT.

Eligibility criteria: Key Inclusion Criteria:

* Fully understand and voluntarily sign informed consent. 3-35years old. At least one legal guardian and/or Subjects to sign informed consent.
* Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β+, β+β0, βEβ0 genotype.
* Subjects with no affection with HIV, TP, HBV, HCV, CMV and EBV.
* Subjects body condition eligible for autologous stem cell transplant.

Key Exclusion Criteria:

* Subjects acceptable for allogeneic hematopoietic stem cell transplantation and have an available fully matched related donor.
* Active bacterial, viral, or fungal infection.
* Treated with erythropoietin prior 3 months.
* Immediate family member with any known hematological tumor.
* Subjects with severe psychiatric disorders to be unable to cooperate.
* Prior hematopoietic stem cell transplant (HSCT).

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Proportion of stem cell engrafted subjects
timeFrame: Within 42 Days After BRL-101 Infusion
measure: Time to neutrophil engraftment
timeFrame: Up to 12 Months After BRL-101 Infusion
measure: Frequency, severity, and relationship to BRL-101 of adverse events over 12 months following BRL-101 infusion
timeFrame: Up to 12 Months After BRL-101 Infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Tianjin
country: China
facility: Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Bioray Laboratories
name: Xiaochen Wang, PhD
role: STUDY_CHAIR
References: