A Clinical Study Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia

A Clinical Study Evaluating the Safety and Efficacy of Ex-vivo tBE Edited Autologous Hematopoietic Stem Progenitor Cells (CS-101) in Treating Subjects With β-thalassemia

The goal of this open label, single-arm clinical study is to learn about the safety and efficacy of CS-101 in treating β-thalassemia.

Study Overview

• Status: Completed
• Conditions: Beta-Thalassemia
• Intervention / Treatment: Biological: CS-101

Detailed Description

CS-101 is an autologous CD34+ cell suspension, edited by ex vivo base editing technology, which modifies the BCL11A binding site in HBG promoter, so that it loses the ability to bind to BCL11A, which can re-induce the production of γ-globin chain and increase the concentration of fetal hemoglobin(HbF) in the blood, compensating for the function of missing adult hemoglobin HbA to achieve clinical cure. The therapy addresses two major challenges in the current treatment of the disease: lack of matching donors and graft-versus-host diseases in allogeneic hematopoietic stem cell transplantation.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Nanning, China
    • The First Affiliated Hospital of Guangxi Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria：

• 6 to 35 years old(inclusive) male or female subjects at the time of informed consenting
• Diagnosis of β-thalassemia, genotypes include but are not limited to β+β0，βEβ0，β0β0, etc
• History of at least≥8 units/year of packed RBC transfusions in the prior 12 months prior to the screening period
• Generally in good condition, Karnofsky performance score≥60 points for subjects≥16 years old at the time of autologous hematopoietic stem cell collection, or Lansky Play-Performance score≥60 points for subjects under 16 years old, or equivalent clinical evaluation as the investigator site's common practice

Key Exclusion Criteria:

• Treatment with other investigational medications or other experimental interventions 30 days prior to signing informed consent or within 6 half-lives of the drug, whichever is longer.
• Subjects who have received or are receiving thalidomide and/or Luspatercept, when their drug-drug interaction on the efficacy and safety of CS-101 cannot be ruled out, unless at least there are 3 test results showing the total hemoglobin level before transfusion is below 9g/dL in the past 6 months before screening.
• Previously received allogeneic hematopoietic stem cell transplantation or gene(edited) therapy.
• Subjects have available related fully matching donors and are eligible and prepared for allogeneic hematopoietic stem cell transplantation.
• Those with active infections, including but not limited to: HIV, hepatitis B, hepatitis C, cytomegalovirus, Epstein-Barr virus and treponema pallidum test positive, or known tuberculosis, parasitic infection, etc. who are judged by the investigator to be unsuitable to participate in this study.
• Echocardiography results with ejection fraction below 45%.
• Advanced liver disease, defined as：

Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) or:

Baseline International Normalized Ratio (INR) >1.5 × ULN.

• MRI during the screening period showed heavy iron overload and is judged by the investigator to be unable to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CS-101; CS-101: Autologous CD34+ hematopoietic stem cell suspension modified by ex vivo base editing technique	Biological: CS-101; Autologous CD34+ hematopoietic stem cell suspension modified by ex vivo base editing technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of adverse events(AEs）as assessed by CTCAE v5.0		From signing informed consent to 12 months post-CS-101 infusion
Proportion of subjects with engraftment	Subjects with engraftment is defined as neutrophil engrafted	within 42 days post-CS-101infusion
Incidence of transplant-related mortality		From baseline to 100 days post-CS-101 infusion
All-cause mortality		From signing informed consent to 12 months post-CS-101 infusion
Proportion of subjects achieving transfusion independence for at least 6 consecutive months		From 3 months up to 12 months post-CS-101 infusion
Time to last red blood cell(RBC) transfusion		Days post-CS-101 infusion
Time to neutrophil and platelet engraftment	Time to neutrophil engraftment is defined as first day of 3 consecutive measurements of absolute neutrophil count≥0.5×10^9/L on three different days； Time to platelet engraftment is defined as first day of 3 consecutive measurements of absolute platelet count≥20×10^9/L on three different days and without platelet transfusion in the past 7 days；	Days post-CS-101 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total hemoglobin(Hb) concentration over time	Total hemoglobin concentration change from baseline to 12 months post-CS-101 infusion	up to 12 months post-CS-101 infusion
Chimerism level in Peripheral blood and bone marrow	Proportion of alleles with intended genetic modification in peripheral blood leukocytes and bone marrow over time	up to 12 months post-CS-101 infusion
Change in fetal hemoglobin(HbF) concentration over time	fetal hemoglobin concentration change from baseline to 12 months post-CS-101 infusion	up to 12 months post-CS-101 infusion

Collaborators and Investigators

• Sponsor: CorrectSequence Therapeutics Co., Ltd
• Collaborators: First Affiliated Hospital of Guangxi Medical University
• Investigators: Principal Investigator: Yongrong Lai, M.D., First Affiliated Hospital of Guangxi Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2023
• Primary Completion (Actual): July 1, 2025
• Study Completion (Actual): July 1, 2025

Study Registration Dates

• First Submitted: August 23, 2023
• First Submitted That Met QC Criteria: August 29, 2023
• First Posted (Actual): September 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; beta-Thalassemia
• Other Study ID Numbers: CS-101-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No