Safety and Efficacy Evaluation of γ-globin Reactivated Autologous Hematopoietic Stem Cells

February 26, 2024 updated by: Bioray Laboratories

an Open Label Trial of Evaluation of the Safety and Efficacy of Treatment With γ-globin Reactivated Autologous Hematopoietic Stem Cells in Subjects With β-thalassemia Major

This is a single arm, open label, single-dose, phase 1/2 study in up to 5 participants with β-thalassemia major.The study will evaluate the safety and efficacy of the treatment with γ-globin reactivated autologous hematopoietic stem cells in subjects with β-thalassemia major.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Suspended

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

γ-globin reactivated autologous hematopoietic stem cells will be manufactured using Glycosylase Base Editors. Subject participation for this study will be 2 year. Subjects who enroll in this study will be asked to participate in a subsequent long-term follow up study that will monitor the safety and efficacy of the treatment they receive for up to 15 years post-transplant.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: lai yongrong, PhD
  • Phone Number: 07715350031
  • Email: yfyxck@163.com

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200241
        • Shanghai Bioray Laboratories Inc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Key inclusion criteria:

  • Fully understand and voluntarily sign informed consent. 3-35years old. At least one legal guardian and/or Subjects to sign informed consent.

  • Clinically diagnosed as β-thalassemia major, phenotypes including β0β0, β+β+、β

    +β0, βEβ0 genotype.

  • Subjects with no affection with EBV, HIV, CMV, TP, HAV, HBV and HCV.
  • Subjects body condition eligible for autologous stem cell transplant.

Key exclusion criteria:

  • Subjects acceptable for allogeneic hematopoietic stem cell transplantation and have an available fully matched related donor.
  • Active bacterial, viral, or fungal infection.
  • Treated with erythropoietin prior 3 months.
  • Immediate family member with any known hematological tumor.
  • Subjects with severe psychiatric disorders to be unable to cooperate.
  • Recently diagnosed as malaria.
  • History of complex autoimmune disease.
  • Persistent aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin value >3 X the upper limit of normal (ULN).
  • Subjects with severe heart, lung and kidney diseases.
  • With serious iron overload, serum ferritin>5000mg/ml.
  • Any other condition that would render the subject ineligible for HSCT, as determined by the attending transplant physician or Investigator.
  • Subjects who are receiving treatment from another clinical study, or have received another gene therapy.
  • Subjects or guardians had resisted the guidance of the attending doctor.
  • Subjects whom the investigators do not consider appropriate for participating in this clinical study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: γ-globin reactivated autologous hematopoietic stem cells
each subject will accept one dose of γ-globin reactivated autologous hematopoietic stem cells
Biological: γ-globin reactivated autologous hematopoietic stem cells
gene edited autologous hematopoietic stem cells with γ-globin expression; BRL-103

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of subjects achieving successful neutrophil engraftment within 42 days after BRL-103 infusion
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Time to neutrophil engraftment
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Time to platelet engraftment
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Frequency and severity of adverse events through 100 days after BRL-103 Infusion
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion reduction for at least 3 months (TR3)
Time Frame: From 12 months to 24 months post transplant
TR3 was defined as at least a 50% reduction in monthly red blood cell transfusion volume and transfusion frequency compared to baseline for at least 3 months
From 12 months to 24 months post transplant

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of subjects achieving sustained transfusion independence for at least 3 months (TI3)
Time Frame: From 12 months to 24 months post transplant
Routine transfusion without disease related and with Hb ≥ 90 g/L for at least 3 months
From 12 months to 24 months post transplant
Proportion of subjects achieving TR6
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Proportion of subjects achieving TR12
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion independence for at least 6 months (TI6)
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Proportion of subjects achieving sustained transfusion independence for at least 12 months (TI12)
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Incidence of transplant related mortality (TRM) within 100 days and within 1 year
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Frequency, severity, and relationship to BRL-103 of adverse events over two years following BRL-103 infusion.
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
All-cause mortality
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Proportion of alleles with intended genetic modification present in peripheral blood leukocytes over time
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Fetal hemoglobin concentration (pre-transfusion) over time
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Total hemoglobin concentration (pre-transfusion) over time
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
Change in serum ferritin level from baseline over time
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
Changes in the proportion of red blood cells expressing HbF in the blood circulation
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant
LDH levels over time
Time Frame: From 12 months to 24 months post transplant
From 12 months to 24 months post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bioray Laboratories

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
First Affiliated Hospital of Guangxi Medical University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: lai yongrong, PhD, First Affiliated Hospital of Guangxi Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 25, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 8, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 23, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 5, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 26, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2021-BRL-103

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

clinical study protocol will be shared after Estimated Primary Completion Date

IPD Sharing Time Frame

data will be available before 2023.10.1, one week long

IPD Sharing Access Criteria

university and institute

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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