CS-101 in Patients With β-thalassemia

Beta-Thalassemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06328764
• Other study ID #: CS-101-11
• Status: Enrolling by invitation
• Phase: Early Phase 1
• Start date: March 19, 2024
• Est. completion date: January 30, 2026

Study information

• Verified date: May 2024
• Source: CorrectSequence Therapeutics Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

CS-101 is an autologous CD34+ cell suspension, edited by in vitro 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 10
• Est. completion date: January 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 35 Years

Eligibility

Inclusion Criteria:

• 6 to 35 years old(inclusive) male or female subjects at the time of informed consenting Diagnosis of ß-thalassemia, genotypes include but are not limited to ß+ß0,ßEß0,ß0ß0, 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

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.

Related Conditions & MeSH terms

• Beta-Thalassemia
• Thalassemia

Intervention

Genetic:
• CS-101
Autologous CD34+ hematopoietic stem cell suspension modified by in vitro base editing technique

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi

Sponsors (2)

Lead Sponsor	Collaborator
CorrectSequence Therapeutics Co., Ltd	First Affiliated Hospital of Guangxi Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of adverse events(AEs)as assessed by CTCAE v5.0		From signing informed consent to 12 months post-CS-101 infusion
Primary	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
Primary	Proportion of subjects with engraftment	Subjects with engraftment is defined as neutrophil engrafted	within 42 days post-CS-101infusion
Primary	Incidence of transplant-related mortality		From baseline to 100 days post-CS-101 infusion
Primary	All-cause mortality		From signing informed consent to 12 months post-CS-101 infusion
Primary	Proportion of subjects achieving transfusion independence for at least 6 consecutive months		From 3 months up to 12 months post-CS-101 infusion
Primary	Time to last red blood cell(RBC) transfusion		Days post-CS-101 infusion
Secondary	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
Secondary	Change in fetal hemoglobin(HbF) concentration over time	?-globin concentration change from baseline to 12 months post-CS-101 infusion	up to 12 months post-CS-101 infusion
Secondary	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