Transfusion-dependent Beta-Thalassemia
Conditions
Keywords
gene therapy, lentiviral vector, KL003 cell injection, transfusion-dependent β-thalassemia
Brief summary
This is a non-randomized, open label, single-dose study in up to 41 participants with β-thalassemia major. The goal of this clinical trial is to evaluate the safety and efficacy of KL003 cell injection in subjects with β-thalassemia major.
Detailed description
This is a single-arm, multi-site, single-dose, Phase 1/2 study to assess KL003 Cell Injection in up to 41 participants with transfusion-dependent β-thalassemia (TDT) who are ≥3 and ≤35 years of age. KL003 Cell Injection is autologous CD34+ stem cells transduced Ex Vivo with a lentiviral Vector encoding βA-T87Q-Globin.
Interventions
Administered by intravenous infusion after myeloablative conditioning with busulfan.
Sponsors
Kanglin Biotechnology (Hangzhou) Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Male or female age between 3-35 years; * Diagnosis of transfusion-dependent β-thalassemia and a history of at least 100 mL/kg/year of pRBCs or ≥8 transfusions of pRBCs per year for the prior 2 years; * Karnofsky performance status ≥70 for participants≥16 years of age; Lansky performance status of ≥70 for participants\<16 years of age; * Eligible to undergo auto-HSCT; * Willing and able to follow the research procedures and conditions, with good compliance; * Willing to receive at least the 2 years follow-up; * Participant and/or legal guardians voluntarily participated in this clinical trial and signed the informed consent form.
Exclusion criteria
* Diagnosis of composite α thalassemia; * Prior receipt of gene therapy or allo-HSCT; * Meet the criteria for allo-HSCT and with an identified willing donor with full HLA match; * Participants with severe iron overload at the time of screening; * Presence of unusual antibody of red blood cell antigens or tested positive for platelet antibody; * Known allergy to clinical trial drug (plerixafor or G-CSF or busulfan) or ingredient(DMSO etc.); * Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the clinical investigator; * Subjects positive with the following etiological tests: human immunodeficiency virus(HIV-1-2),human cytomegalovirus (HCMV-DNA),EB virus（EBV-DNA）,HBV (HBsAg/HBV-DNA positive),HCV antibody (HCV-Ab), Human T-lymphotropic virus antibody (HTLV-Ab), Treponema pallidum antibody (TP-Ab); * Uncorrectable coagulation dysfunction or history of severe bleeding disorder; * History of major organ damage including: 1. Liver function test suggest AST or ALT levels \>3× upper limit of normal（ULN）; 2. Total serum bilirubin value\>2.5×ULN;if combined with Gilbert syndrome, total bilirubin\>3×ULN and direct bilirubin value\>2.5×ULN; 3. Left ventricular ejection fraction \<45%; 4. Baseline calculated eGFR\<60mL/min/1.73m2; 5. Pulmonary function:FEV1/FVC\<60% and/or diffusion capacity of carbon monoxide (DLco) \<60% of prediction;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numbers of Participants With Vector-Derived Replication-Competent Lentivirus (RCL) | From time of KL003 infusion through Month 24 | Peripheral blood samples were analyzed for detection of RCL |
| Engraftment time of neutrophil and platelet | From time of KL003 infusion through Month 24 | Neutrophil engraftment was defined as the first day when neutrophils ≥ 0.5×10\^9/L for 3 consecutive days; Platelet engraftment was defined as the first the first day of platelet count ≥ 20.0×10\^9/L for 7 consecutive days with no platelet transfusions. |
| Overall Survival | From time of KL003 infusion through Month 24 | Overall survival was defined as time from date of KL003 infusion to date of death. |
| The number, frequency and severity of adverse events (AE) within 1 year after infusion of KL003 drug products | From time of KL003 infusion through Month 24 | Frequency and severity of AEs & SAEs identified according to NCI CTCAE 5.0 |
| Clonal dominance or secondary tumors caused by lentiviral vector insertional-mutation | From time of KL003 infusion through Month 24 | Clonal dominance was defined as an ISA result greater than 90% of the total insertion sites (IS) at any time |
| KL003 engraftment | From time of KL003 infusion through Month 2 | Proportion of participants with successful engraftment within 42 days after KL003 infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of participants achieved TI 12 | From time of KL003 infusion through Month 24 | TI 12 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 12 months |
| The start time of Transfusion Independence (TI) after KL003 infusion | From time of KL003 infusion through Month 24 | The TI start time is defined as the first day of treated participants with transfusion-dependent β-thalassemia (TDT) who achieved transfusion independence. |
| Total Hb and the vector-derived HbA^T87Q | From time of KL003 infusion through Month 24 | The total Hb is measured by routine blood test, Therapeutic globin expression was measured by HbA\^T87Q in peripheral blood. |
| The proportion of participants achieved Transfusion Independence (TI)for at least 6 months | From time of KL003 infusion through Month 24 | TI 6 is defined as Hb ≥ 90.0 g/L after reinfusion and without disease-related routine blood transfusion for 6 months |
Countries
China
Contacts
Primary Contactjingfeng Yan
Outcome results
None listed