Alpha Thalassemia Hemoglobin H Constant Spring, Hemoglobinopathies, Hereditary Diseases
Conditions
Keywords
RM-004, Hemoglobin H-Constant Spring disease, Alpha-Thalassemia, Gene therapy, CBE
Brief summary
The purpose of this study is to evaluate the safety and efficacy of RM-004 for Hemoglobin H-Constant Spring disease.
Detailed description
This is a non-randomized, one-arm, open label study to evaluate the safety and efficacy of RM-004 for autologous hematopoietic stem cell transplantation (HSCT) for the treatment of Hemoglobin H-Constant Spring disease. Five subjects aged from 12 to 35 years will be recruited in this study.
Interventions
GENETICRM-004
Intravenous infusion of gene-edited CD34+autologous hematopoietic stem cells (RM-004) after myeloablative conditioning with busulfan.
Sponsors
Guangzhou Reforgene Medicine Co., Ltd.
The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects voluntarily sign informed consent by themselves or their legal guardians and complete the study procedures, follow-up examination and treatment. 2. At the time of screening, subjects should be aged from 12 to 35 years old, regardless of gender. 3. History of at least 100 mL/kilograms (kg)/year of packed red blood cells (pRBC) transfusions in the prior 2 years before screening. 4. Subjects diagnosed with Hemoglobin H-Constant Spring disease (--/ααCS) with HBA2 c.427T\>C mutation.
Exclusion criteria
1. Subject who has an available HLA-matched/well-matched HSCT donor for allogeneic hematopoietic stem cell transplantation (HSCT). 2. Prior HSCT or gene therapy. 3. History of severe hemorrhagic disease. 4. Clinically significant active bacterial, viral, fungal or parasitic infections per investigator's judgement at the time of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with engraftment | Within 42 days after RM-004 infusion | Proportion of subjects with successful neutrophil engraftment (first day of 3 consecutive measurements of absolute neutrophil count \[ANC\] ≥0.5×10\^9/L on 3 different days) after RM-004 infusion. |
| Safety of RM-004 infusion | From signing of informed consent up to 24 months after RM-004 infusion | Number of subjects with adverse events (AEs) and serious adverse events (SAEs) |
| Proportion of subjects who achieve transfusion independence | Up to 24 months after RM-004 infusion | Transfusion independence (TI) was defined as a weighted average hemoglobin (Hb) ≥ 9 g/dL without any red blood cells transfusions for a continuous period of ≥12 months at any time during the study after RM-004 infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of all-cause mortality | From signing of informed consent up to 24 months after RM-004 infusion | Incidence of all-cause mortality |
| Proportion of subjects who stop receiveing transfusion ≥ 6 months | Up to 24 months after RM-004 infusion | Proportion of subjects who stop receiveing transfusion ≥ 6 months |
| Duration of transfusion independence | Up to 24 months after RM-004 infusion | Duration of TI was calculated as the time from the start of TI up to the last available Hb at which the TI criteria are still met. Time period of TI will start when subjects achieve a Hb ≥ 9 g/dL with no transfusions in the preceding 60 days |
Countries
China
Contacts
Primary ContactXinhua Zhang, MD
Outcome results
None listed