Safety and Efficacy of RM-004 Cells for Hemoglobin H-Constant Spring Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of RM-004 for Hemoglobin H-Constant Spring disease.

Detailed Description
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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.

Official Title
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Study to Evaluate the Safety and Efficacy of RM-004 Cells for the Treatment of Hemoglobin H-Constant Spring Disease

Conditions
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Alpha Thalassemia Hemoglobin H Constant Spring, Hemoglobinopathies, Hereditary Diseases

Intervention / Treatment
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* Genetic: RM-004


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily sign informed consent by themselves or their legal guardians and complete the study procedures, follow-up examination and treatment. At the time of screening, subjects should be aged from 12 to 35 years old, regardless of gender. History of at least 100 mL/kilograms (kg)/year of packed red blood cells (pRBC) transfusions in the prior 2 years before screening. Subjects diagnosed with Hemoglobin H-Constant Spring disease (--/ααCS) with HBA2 c.427T>C mutation. Exclusion Criteria: Subject who has an available HLA-matched/well-matched HSCT donor for allogeneic hematopoietic stem cell transplantation (HSCT). Prior HSCT or gene therapy. History of severe hemorrhagic disease. Clinically significant active bacterial, viral, fungal or parasitic infections per investigator's judgement at the time of screening.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RM-004<br>RM-004 (ex vivo gene-edited CD34+ autologous hematopoietic stem cells) will be administered as a single intravenous infusion | Genetic: RM-004<br>* Intravenous infusion of gene-edited CD34+autologous hematopoietic stem cells (RM-004) after myeloablative conditioning with busulfan.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with engraftment | 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. | Within 42 days after RM-004 infusion | 
| Safety of RM-004 infusion | Number of subjects with adverse events (AEs) and serious adverse events (SAEs) | From signing of informed consent up to 24 months after RM-004 infusion | 
| Proportion of subjects who achieve transfusion independence | 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. | Up to 24 months after RM-004 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of all-cause mortality | Incidence of all-cause mortality | From signing of informed consent up to 24 months after RM-004 infusion | 
| Proportion of subjects who stop receiveing transfusion ≥ 6 months | Proportion of subjects who stop receiveing transfusion ≥ 6 months | Up to 24 months after RM-004 infusion | 
| Duration of transfusion independence | 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 | Up to 24 months after RM-004 infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RM-004, Hemoglobin H-Constant Spring disease, Alpha-Thalassemia, Gene therapy, Base editing