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

NCT06065189 | Active Not Recruiting Early Phase 1

• 1 other identifier: CS-101-03
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Beta-Thalassemia

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Occurrence of achieving transfusion independence for at least 3 consecutive months

  From 3 months up to 180 days post-CS-101 infusion

• Time to last red blood cell(RBC) transfusion

  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

  up to 180 days post-CS-101 infusion

Study Arms (1)

CS-101 injection

EXPERIMENTAL

Autologous CD34+(cluster of differentiation 34) hematopoietic stem cell suspension modified by in vitro base editing technique

Biological: CS-101 injection

Interventions

CS-101 injection BIOLOGICAL

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

CS-101 injection

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

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, 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

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• CorrectSequence Therapeutics Co., Ltd: collaborator

Study Sites (1)

Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, 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

• Xiaowen Zhai, M.D.

  Children's Hospital of Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 3, 2023
• Study Start: November 7, 2023
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)