Clinical trial NCT06024876: A Clinical Study Evaluating the Safety and Efficacy of CS-101 in Treating Subjects With β-thalassemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Beta-Thalassemia
Lead sponsor: CorrectSequence Therapeutics Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: First Affiliated Hospital of Guangxi Medical University
First posted: 2023-09-06
Enrollment: 5
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 β-thalassemia.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency and severity of adverse events(AEs）as assessed by CTCAE v5.0
timeFrame: From signing informed consent to 12 months post-CS-101 infusion
measure: Time to neutrophil and platelet engraftment
timeFrame: Days post-CS-101 infusion
measure: Proportion of subjects with engraftment
timeFrame: within 42 days post-CS-101infusion
measure: Incidence of transplant-related mortality
timeFrame: From baseline to 100 days post-CS-101 infusion
measure: All-cause mortality
timeFrame: From signing informed consent to 12 months post-CS-101 infusion
measure: Proportion of subjects achieving transfusion independence for at least 6 consecutive months
timeFrame: From 3 months up to 12 months post-CS-101 infusion
measure: Time to last red blood cell(RBC) transfusion
timeFrame: Days post-CS-101 infusion
Secondary outcomes:
measure: Change in total hemoglobin(Hb) concentration over time
timeFrame: up to 12 months post-CS-101 infusion
measure: Change in fetal hemoglobin(HbF) concentration over time
timeFrame: up to 12 months post-CS-101 infusion
measure: Chimerism level in Peripheral blood and bone marrow
timeFrame: up to 12 months post-CS-101 infusion
Other outcomes:
Locations:
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
Study officials:
affiliation: First Affiliated Hospital of Guangxi Medical University
name: Yongrong Lai, M.D.
role: PRINCIPAL_INVESTIGATOR
References: