Safety and Efficacy Evaluation of BRL-101 in Subjects With Transfusion-Dependent β-Thalassemia

• ClinicalTrials.gov Identifier: NCT05577312
• Recruitment Status: Enrolling by invitation
• First Posted: October 13, 2022
• Last Update Posted: March 4, 2024
• Sponsor: Bioray Laboratories
• Collaborators: First Affiliated Hospital of Guangxi Medical University; Xiangya Hospital of Central South University; Chinese Academy of Medical Sciences; Nanfang Hospital, Southern Medical University
• Information provided by (Responsible Party): Bioray Laboratories

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Beta-Thalassemia	Drug: BRL-101	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 1, 2022
• Estimated Primary Completion Date: August 4, 2025
• Estimated Study Completion Date: September 10, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: BRL-101; BRL-101 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the erythroid lineage-specific enhancer of the BCL11A gene). Subjects will receive a single infusion of BRL-101.	Drug: BRL-101; CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A enhancer site; Other Name: BRL-101 autologous hematopoietic stem and progenitor cells injection

Outcome Measures

Primary Outcome Measures :

1. Proportion of stem cell engrafted subjects [ Time Frame: Within 42 Days After BRL-101 Infusion ]
   Stem cell engraftment was defined as an absolute peripheral blood neutrophil count of ≥ 0.5 × 109/L for 3 consecutive days within 42 days following BRL-101 intravenous infusion.
2. Time to neutrophil engraftment [ Time Frame: Up to 12 Months After BRL-101 Infusion ]
   Defined as Day 1 of absolute peripheral blood neutrophil count ≥ 0.5 × 109/L for 3 consecutive days
3. Frequency, severity, and relationship to BRL-101 of adverse events over 12 months following BRL-101 infusion [ Time Frame: Up to 12 Months After BRL-101 Infusion ]
   Adverse events assessed according to NCI-CTCAE v5.0 criteria

Eligibility Criteria

• Ages Eligible for Study: 3 Years to 35 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

China, Guangdong

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China, 510510

China, Guangxi

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China, 530021

China, Hunan

Xiangya Hospital of Central South University

Changsha, Hunan, China, 510510

China, Tianjin

Chinese Academy of Medical Sciences

Tianjin, Tianjin, China

Sponsors and Collaborators

Bioray Laboratories

First Affiliated Hospital of Guangxi Medical University

Xiangya Hospital of Central South University

Chinese Academy of Medical Sciences

Nanfang Hospital, Southern Medical University

Investigators

• Study Chair: Xiaochen Wang, PhD; Bioray Laboratories

More Information

• Responsible Party: Bioray Laboratories
• ClinicalTrials.gov Identifier: NCT05577312
• Other Study ID Numbers: 2022-BRL-101
• First Posted: October 13, 2022
• Last Update Posted: March 4, 2024
• Last Verified: January 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bioray Laboratories:

Transfusion-Dependent β-Thalassemia

Additional relevant MeSH terms:

Thalassemia; beta-Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn