Evaluating CS-101 for treating β-thalassemia major

A Single-arm, Open-label Phase I Clinical Trial to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamic Profile of a Single Dose of CS-101 Injection in Subjects With β-thalassemia Major

This study is testing a new treatment called CS-101 to see if it can help people with β-thalassemia major by boosting their production of fetal hemoglobin to improve their anemia.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 12 Years to 35 Years
• Sex: All
• Sponsor: CorrectSequence Therapeutics Co., Ltd (Industry-sponsored)
• Locations: 3 sites (Nanning, Guangxi and 2 other locations)
• Trial ID: NCT06291961 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm clinical study aims to assess the safety and efficacy of CS-101, an autologous CD34+ cell suspension, in patients with β-thalassemia major anemia. The treatment utilizes in vitro base editing technology to modify the BCL11A binding site in the HBG promoter, enhancing the production of fetal hemoglobin (HbF) to compensate for the absence of adult hemoglobin (HbA). By addressing challenges such as donor matching and graft-versus-host disease, this innovative approach seeks to provide a clinical cure for affected individuals.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 12 to 35 diagnosed with β-thalassemia major who are generally in good health.

Not a fit: Patients who are currently receiving other investigational medications or have severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life and health outcomes for patients with β-thalassemia major.

How similar studies have performed: While this approach is innovative, similar studies using gene editing technologies have shown promise in treating genetic blood disorders.

Eligibility criteria

Inclusion Criteria:

* 12 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

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 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
* Pregnant or lactating women

Where this trial is running

Nanning, Guangxi and 2 other locations

• The First Affiliated Hospital of Guangxi Medical University — Nanning, Guangxi, China (Recruiting)
• Children's Hospital of Fudan University — Shanghai, Shanghai, China (Recruiting)
• Ruijin Hospital Shanghai JiaoTong University School of Medicine — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Yaliang Li

Conditions Beta-Thalassemia Major