Safety and Efficacy Evaluation of Autologous CRISPR-Cas12b Edited Hematopoietic Stem Cells

October 16, 2023 updated by: Jun Shi, Institute of Hematology & Blood Diseases Hospital, China

A Study to Evaluate the Efficacy and Safety of Autologous CRISPR-Cas12b Edited Hematopoietic Stem Cells in Transfusion-dependent β Thalassemia Patients

This is a single-arm, open, single-injection exploratory clinical study with two transfusion-dependent β thalassemia (β-TDT) participants planned to enroll.

Study Overview

Status

Status

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

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

Through CRISPR-Cas 12b editing tool with independent intellectual property rights of Chinese Academy of Sciences, HBG1/2 promoter was edited to reactivate gamma-globin and induce fetal hemoglobin (HbF) expression. This leads to a subsequent reduction in ineffective red blood cell production (due to a reduction in the uncompounded alpha-globin chain) and improved red blood cell survival (due to reduced hemolysis), ultimately improving the sequelae of anemia and reducing the need for transfusion. Safety and efficacy will be evaluated continuously throughout the study, follow-up was up to 24 months. After the end of this trial, participants who received the infusion of autologous CRISPR-Cas12b edited hematopoietic stem cells (VGB-Ex01) will be invited to participate in the long-term follow-up study to complete the 15-year follow-up plan.

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.
2

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 Locations

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

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 3-35 years old (inclusive), male or female;
  • The subject and/or his/her legally recognized representative/parent/guardian fully understands the study and all information related to the study and has signed the informed consent form;
  • Clinical diagnosis of transfusion-dependent β-thalassemia (TDT) with a blood transfusion record within 2 years (inclusive) prior to screening showing a history of ≥ 10 units (U)/kg/year (or ≥ 100 mL/kg/year) or ≥ 8 times/year of suspended RBC transfusions in at least 1 consecutive 12-month period;
  • Karnofsky score (for subjects aged ≥ 16 years) or Lansky score (for subjects aged < 16 years) of ≥ 80;
  • Subjects in stable disease state who are eligible for hematopoietic stem cell transplantation as per investigator's judgment;
  • Access to diagnosis and treatment records issued by medical professional institutions within 2 years prior to screening, including the records of blood transfusions, hematology, serum chemistry, and other examinations;
  • Willing and able to comply with study procedures, with good compliance, and willing to receive and complete the follow-up study with a duration of at least 2 years;
  • Subjects of childbearing potential (including female subjects of childbearing potential and male subjects whose partners are of childbearing potential) must use effective contraception within 12 months of treatment.

Exclusion Criteria:

  • Diagnosis of associated α-thalassemia: > 1 alpha chain deletion or alpha gene functional defect;
  • Have available HLA-fully matched donors and acceptable for allogeneic hematopoietic stem cell transplantation;
  • Irregular antibody or platelet antibody positive;
  • Prior allogeneic bone marrow transplantation or gene therapy;
  • Subjects with clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator at screening, including but not limited to those with positive etiology of human immunodeficiency virus (HIV-1/2), human cytomegalovirus (HCMV-DNA), Epstein-Barr virus (EBV-DNA), or Treponema pallidum antibody (TP-Ab), or with previous hepatitis B or C infection;
  • Subjects with an injury of major organs
  • Contraindications for hematopoietic stem cell collection and poor collection efficiency judged by the investigator;
  • Contraindications to the clinical investigational product and its excipients, G-CSF (hematopoietic stem cell mobilization), plerixafor (hematopoietic stem cell mobilization), busulfan (myeloablation), and other drugs;
  • Participation within 3 months prior to screening or current participation in another interventional clinical study;
  • History or family history of malignancy or myeloproliferative disorder;
  • History of uncontrollable epilepsy, mental disorder, or other psychiatric disorders;
  • Abuse of psychoactive substance, drug, or alcohol within 6 months prior to enrollment;
  • Pregnant or breastfeeding females;
  • Other diseases or reasons that interfere with study procedures;
  • Any other conditions that the investigator deems unsuitable for the subject's participation in the 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: VGB-Ex01
Each subject will accept one dose of VGB-Ex01.
Biological: VGB-Ex01
CRISPR-Cas12b editing hematopoietic stem cells

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
Incidence of adverse events and serious adverse events
Time Frame: Baseline up to 24 months
An adverse event is any untoward medical occurrence in a clinical investigation/participant administered a product; the event will not need to have a causal relationship with the treatment. A serious adverse event is any untoward medical occurrence at any dose that resulted in death; life threatening;require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect.
Baseline up to 24 months
Number of subjects with neutrophil implantation ≤ 42 days
Time Frame: Baseline up to 42 days
Neutrophil implantation was defined as 3 consecutive days with 3 tests for ANC≥500/μL.
Baseline up to 42 days

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
Number of subjects transfusion independence (TI) for at least 6 months after transfusion
Time Frame: Baseline up to 6 months
TI defined as Hb≥9g/dL without red blood cell infusion
Baseline up to 6 months
Number of subjects transfusion independence (TI) for at least 12 months after transfusion
Time Frame: Baseline up to 12 months
TI defined as Hb≥9g/dL without red blood cell infusion
Baseline up to 12 months
Fetal hemoglobin (HbF) concentration
Time Frame: Baseline up to 24 months
Changes in HbF concentration from baseline after transfusion
Baseline up to 24 months
Total hemoglobin (Hb) concentration
Time Frame: Baseline up to 24 months
Changes in Hb concentration compared with baseline after transfusion
Baseline up to 24 months
The proportion of circulating red blood cells
Time Frame: Baseline up to 24 months
Changes in the proportion of circulating red blood cells expressing fetal hemoglobin compared to baseline
Baseline up to 24 months

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.
Institute of Hematology & Blood Diseases Hospital, China

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.
Shanghai Vitalgen BioPharma Co., Ltd.

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: Jun Shi, PhD, Institute of Hematology & Blood Diseases Hospital, China

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.
August 31, 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.
December 31, 2025

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.
June 30, 2026

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 11, 2023

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.
September 11, 2023

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.
September 18, 2023

Study Record Updates

Last Update Posted (Actual)

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.
October 17, 2023

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.
October 16, 2023

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.
October 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.
  • VGB-Ex01-001

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

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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