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

Sponsor

The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army (Other)

Overall Status

Recruiting

CT.gov ID

NCT06107400

Collaborator

Guangzhou Reforgene Medicine Co., Ltd. (Other)

Enrollment

Location

Arm

36.8

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Alpha Thalassemia Hemoglobin H Constant Spring Hemoglobinopathies Hereditary Diseases	Genetic: RM-004	Early Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 8, 2023

Anticipated Primary Completion Date :

Oct 31, 2025

Anticipated Study Completion Date :

Oct 31, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: RM-004

RM-004 (ex vivo gene-edited CD34+ autologous hematopoietic stem cells) will be administered as a single intravenous infusion

Genetic: RM-004

Intravenous infusion of gene-edited CD34+autologous hematopoietic stem cells (RM-004) after myeloablative conditioning with busulfan.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.