Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major

Evaluation and Promotion of Key Technologies of Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major

The goal of this open label, single-arm clinical study is to learn about the safety and efficacy of base-edited autologous hematopoietic stem cell transplantation(CS-101) in treating patients with β-thalassemia major.

Study Overview

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

Detailed Description

CS-101 is an autologous CD34+ cell suspension modified by ex vivo base editing technology, removing the inhibitory effect of BCL11A on the γ-globin coding gene, inducing the production of γ-globin chains, increasing the concentration of fetal hemoglobin (HbF) in the blood, compensating for the loss of adult hemoglobin (HbA) to treat transfusion-dependent type/ Major β - thalassemia. The therapy addresses two major challenges in the treatment of the disease: lack of matching donors and graft-versus-host responses commonly seen in allogeneic hematopoietic stem cell transplantation.

The study consists of the following five phases:

Screening phase: Sign informed consent, complete screening assessments, and confirm the eligibility for enrollment; Baseline: check the subject's baseline status; Mobilization, collection and manufacturing phase: mobilize, collect autologous CD34+ cells and manufacture, release and transport CS-101 product; Conditioning and treatment phase: including myeloablation and CS-101 product infusion; Follow-up phase: 180 days post-infusion.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201102
      • Children's Hospital of Fudan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 3 to 17 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
• 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
• For female subjects of childbearing potential: use effective contraceptive measures for at least 1 month prior to screening and agree to continue using such measures for contraception throughout the study
• For male subjects who have a potential ability to father a child: use condoms or other methods continuously from the start of mobilization to ensure effective contraception for sexual partners during the study period

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.
• Subjects with coexisting α-thalassemia and more than 2 deletions or non-deletional mutations in the α-globin chain coding genes.
• Known to be allergic to drugs used during autologous hematopoietic stem cell transplantation (including but not limited to granulocyte colony-stimulating factor, busulfan, dextran), excipients(such as dimethyl sulfoxide), or instruments(such as intravenous catheters) as determined by the investigator are deemed unsuitable to participate in this study.
• 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%
• Subjects who are febrile (temperature over 37.3° C) should be held back from enrolment.
• 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.
• Patients with past/present history of cancer
• Known neurological disorders, psychological problems or mental illness, and is judged by the investigator to be unable to cooperate with the study procedures
• Known history of uncontrolled epileptic seizures and is judged by the investigator to be unfit to participate in this study
• Known history of other serious cardiovascular, pulmonary, renal diseases, digestive tract conditions, liver diseases and / or other conditions, etc., and are judged by the investigator to be intolerable or inappropriate for autologous hematopoietic stem cell mobilization, collection, and myeloablative conditioning and infusion
• Pregnant or lactating women

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 injection; Autologous CD34+(cluster of differentiation 34) hematopoietic stem cell suspension modified by in vitro base editing technique	Biological: CS-101 injection; Autologous CD34+ hematopoietic stem cell suspension modified by in vitro 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 180 days post-CS-101 infusion
Occurrence of engraftment	Subjects with engraftment is defined as neutrophil engrafted	within 42 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	Days post-CS-101 infusion
Occurrence of transplant-related death		baseline to 100 days post-CS-101 infusion
Occurrence of all-cause death		From signing informed consent to 180 days post-CS-101 infusion
Occurrence of achieving transfusion reduction for at least 3 consecutive months		From 3 months post -CS-101 infusion to 3 months post -CS-101 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to last red blood cell(RBC) transfusion		Days post-CS-101 infusion
Occurrence of achieving transfusion independence for at least 3 consecutive months		From 3 months up to 180 days post-CS-101 infusion
Change in total hemoglobin(Hb) concentration over time		up to 180 days post-CS-101 infusion
Change in fetal hemoglobin(HbF) concentration over time		up to 180 days 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 180 days post-CS-101 infusion

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: CorrectSequence Therapeutics Co., Ltd
• Investigators: Principal Investigator: Xiaowen Zhai, M.D., Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2023
• Primary Completion (Actual): August 12, 2025
• Study Completion (Actual): August 12, 2025

Study Registration Dates

• First Submitted: September 27, 2023
• First Submitted That Met QC Criteria: September 27, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 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-101-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No