Safety and Efficacy of KL003 Cell Injection in Severe Sickle Cell Disease

It is a single-arm, single-center, open-label, single-dose study. A total of three subjects with severe sickle cell disease (SCD), aged 12-50 years (inclusive), are planned to receive cell infusion. After successful hematopoietic stem cell engraftment is achieved in the first subject, cell infusion will be initiated for subsequent subjects.

Study Overview

• Status: Not yet recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Genetic: KL003 Cell Injection

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 12-50 years of age (inclusive) at the time of screening
• Diagnosed with sickle cell disease (SCD) with a βS/βS, βS/β0 or βS/β+ genotype.
• Experienced at least 4 severe vaso-occlusive events (VOEs) in the two years before informed consent, despite supportive care measures (e.g., a pain management plan).
• Have a Karnofsky Performance Status (KPS) score (for subjects ≥16 years) or Lansky Performance Status (LPS) score (for subjects <16 years) of ≥60.
• Have experienced either hydroxyurea (HU) failure at any time in the past or demonstrated intolerance to HU.
• Subject must have been treated and followed for at least two years before informed consent at the medical center that maintained detailed records of their sickle cell disease history.
• Be willing and able to comply with all study procedures and visit schedules.
• The subject and/or their legally authorized representative must voluntarily agree to participate, sign the informed consent form, and be capable of completing all follow-up assessments required by the protocol.

Exclusion Criteria:

• Have any severe active infection (fungal, bacterial, viral, tuberculosis, or other), including active Hepatitis B (defined as serum HBV-DNA ≥2000 IU/mL), active Hepatitis C virus (HCV) infection, positive human immunodeficiency virus (HIV) antibody, or active syphilis.
• Inadequate bone marrow function, as defined by an absolute neutrophil count of <1.0 x 10^9/L (<0.5 x 10^9/L for subjects on hydroxyurea treatment) or a platelet count <100 x 10^9/L.
• Have severe cerebrovascular disease, including a history of significant ischemic or hemorrhagic stroke, abnormal Transcranial Doppler (TCD) flow velocities requiring chronic transfusion therapy (>200 cm/s), occlusion or stenosis of the circle of Willis, or any history of moyamoya disease.
• Baseline oxygen saturation < 90% without supplemental oxygen (excluding periods of SCD crisis, severe anemia or infection).
• Baseline carbon monoxide diffusing capacity (DLCO) < 50% (corrected for Hb) in the absence of infection. If DLCO cannot be assessed due to age or cognitive limitations, there must be a normal respiratory exam, a chest radiograph without pulmonary infiltrates, and oxygen saturation by pulse oximetry ≥ 90% on room air.
• Baseline left ventricular ejection fraction (LVEF) < 45%
• Clinically significant pulmonary hypertension at baseline, as defined by the requirement for ongoing pharmacologic treatment or the consistent or intermittent use of supplemental oxygen.
• Baseline estimated glomerular filtration rate (eGFR) <70 mL/min/1.73 m^2
• Advanced liver disease
• Have a definite contraindication to stem cell collection.
• Have any prior or current malignancy, myeloproliferative disorder, or immunodeficiency disease.
• Have white blood count <3.0 x 10^9/L and/or platelet count <100.0 x 10^9/L not due to hypersplenism.
• Have a diagnosis of compound alpha-thalassemia (excluding silent carrier).
• Have significant iron overload at screening, defined as severe iron overload on liver MRI, or serum ferritin levels >2000 ng/mL, or cardiac T2* <10 ms.
• Have positive irregular red cell antibodies or platelet antibodies.
• Be eligible for allogeneic hematopoietic stem cell transplantation and have an identified willing, fully HLA-matched donor.
• Prior receipt of gene therapy or allogeneic hematopoietic stem cell transplantation.
• Immediate family member with a known or suspected Familial Cancer Syndrome (including but not limited to hereditary breast and ovarian cancer syndrome, hereditary non-polyposis colorectal cancer syndrome, and familial adenomatous polyposis).
• Have a diagnosed major psychiatric disorder or predisposition that, in the Investigator's opinion, would severely compromise the ability to participate in the clinical study.
• Have an uncorrectable coagulation disorder or a history of severe hemorrhagic disease.
• Have any other condition that, in the opinion of the treating physician, renders the subject unsuitable for hematopoietic stem cell transplantation.
• Have a known allergy to the investigational drug(s) (e.g., plerixafor, busulfan) or their components.
• Have participated in or are currently participating in another interventional clinical study within 3 months before screening.
• Received a live vaccine within 6 weeks before screening.
• Be pregnant or breastfeeding.
• The subject or their partner is unwilling to use medically acceptable effective contraception during the 32-month study period.
• Unable to receive red blood cell transfusion.
• The subject or their parent/guardian is unable to adhere to the study protocol.
• Have any other condition deemed by the Investigator to make the subject unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental; A single intravenous infusion of ≥ 3.0 × 10^6 CD34+ cells/kg was administered.

Genetic: KL003 Cell Injection; KL003 is an autologous CD34⁺ hematopoietic stem cell gene therapy product in which the βA-T87Q-globin gene is transduced via a lentiviral vector. Through genetic modification, the patient's autologous CD34⁺ hematopoietic stem cells are engineered to differentiate into red blood cells expressing functional β-globin, thereby increasing overall hemoglobin levels, improving anemia, and ultimately eliminating transfusion dependence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects who achieve successful engraftment of CD34⁺ cells modified with the βA-T87Q-globin lentiviral vector	Achieving neutrophil engraftment, defined as an absolute neutrophil count ≥ 0.5 × 10^9/L for three consecutive days.	From Day 0 to Day 42 after cell infusion
Incidence and severity of adverse events	Use Common Terminology Criteria for Adverse Events (CTCAE) Version 5 to assess the adverse event	Adverse events will be monitored from baseline through study completion, up to 24 months.

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 14, 2026
• First Submitted That Met QC Criteria: February 23, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell
• Other Study ID Numbers: CP-KL003-006/02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No