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

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

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

Study Overview

• Status: Recruiting
• Conditions: Hemoglobinopathies; Hereditary Diseases; Alpha Thalassemia Hemoglobin H Constant Spring
• Intervention / Treatment: Genetic: RM-004

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 Type: Interventional
• Enrollment (Estimated): 5
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xinhua Zhang, MD; Phone Number: +8613321717386; Email: zxh303@163.com

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army
      • Contact: Xinhua Zhang, MD; Phone Number: +8613321717386; Email: zxh303@163.com

Participation Criteria

Eligibility Criteria

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

Description

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.

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: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army
• Collaborators: Guangzhou Reforgene Medicine Co., Ltd.
• Investigators: Principal Investigator: Xinhua Zhang, MD, The 923rd Hospital of Joint Logistics Support Force of People's Liberation Army

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2023
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: October 25, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Gene therapy; Base editing; RM-004; Hemoglobin H-Constant Spring disease; Alpha-Thalassemia
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Thalassemia; Genetic Diseases, Inborn; Hemoglobinopathies; alpha-Thalassemia
• Other Study ID Numbers: IIT-RM-004-01

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