A Safety and Efficacy Study Evaluating CS-101 in Subjects With β-Thalassemia Major

NCT06291961 | Completed Phase 1

• 1 other identifier: CS-101-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Beta-Thalassemia Major

Outcome Measures

Primary Outcomes (8)

• AEs(Adverse Events) and SAEs(Serious Adverse Events) after CS-101 infusion

  Frequency and severity of adverse events(AEs）as assessed by CTCAE(Common Terminology Criteria for Adverse Events)v5.0

  From signing informed consent to 12 months post-CS-101 infusion

• Overall survival rate

  Up 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-101 infusion

• Time to neutrophil 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.

  Up to 12 months post-CS-101 infusion

• Time to platelet engraftment

  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.

  Up to 12 months post-CS-101 infusion

• Incidence of transplant-related mortality

  Incidence of transplant-related mortality(Transplant-related mortality events defined as deaths assessed by the investigator as potentially transplant-related)

  From baseline to 100 days post-CS-101 infusion

• Change in fetal hemoglobin(HbF) concentration over time

  Fetal hemoglobin(HbF) concentration from baseline to 9 months post-CS-101 infusion

  Up to 12 months post-CS-101 infusion

• Change in total hemoglobin(Hb) concentration over time

  Total hemoglobin concentration change from baseline to 9 months post-CS-101 infusion

  Up to 12 months post-CS-101 infusion

Secondary Outcomes (4)

• Chimerism level in Peripheral blood and bone marrow

  Up to 12 months post-CS-101 infusion

• Proportion of subjects achieving transfusion independence for at least 6 consecutive months

  From CS-101 infusion up to 12 months post-CS-101 infusion

• Proportion of subjects achieving fetal hemoglobin(HbF) increase≥2.0 g/dL

  Up to 2 months post-CS-101 infusion

• Proportion of subjects achieving fetal hemoglobin(HbF) increase≥7.0 g/dL

  Up to 6 months post-CS-101 infusion

Study Arms (1)

CS-101 injection

EXPERIMENTAL

Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique

Genetic: CS-101 injection

Interventions

CS-101 injection GENETIC

Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique

CS-101 injection

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• to 35 years old(inclusive) male or female subjects at the time of informed consenting. For minors, their legal representative is required to sign the informed consent form, besides, if the subjects aged 8 years or older, they should provide a signed and dated.
• Diagnosis of β-thalassemia major.
• Generally in good condition, Karnofsky performance score≥60 points for subjects≥16 years old, or Lansky Play-Performance score≥60 points for subjects under 16 years old.
• For female subjects of childbearing potential: use effective contraceptive measures from the start of 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

You may not qualify if:

• 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 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
• Patients 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 positive results in HIV, cytomegalovirus, Epstein-Barr virus and treponema pallidum test, active infection of hepatitis B, hepatitis C, or known tuberculosis, parasitic infection, etc. Hepatitis B stabilized on medication(HBV-DNA test negative) and cured hepatitis C(HCV-RNA test negative) can be considered acceptable.
• Echocardiography shows ejection fraction below 45%
• Laboratory indicators, 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 shows severe cardiac iron overload and other conditions, and are judged by the investigator to be intolerable or inappropriate for autologous hematopoietic stem cell transplantation
• 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
• The investigators determined that a non-hypersplenism-induced white blood cell count of\<3×10\^9/L, and/or a platelet count of\<100×10\^9/L.
• 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

Sponsors & Collaborators

• CorrectSequence Therapeutics Co., Ltd: lead

Study Sites (3)

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Location

Ruijin Hospital Shanghai JiaoTong University School of Medicine

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

beta-Thalassemia

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Yaliang Li

  CorrectSequence Therapeutics Co., Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: March 4, 2024
• Study Start: April 18, 2024
• Primary Completion: November 17, 2025
• Study Completion: November 17, 2025
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

CN (3)