A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT)

NCT ID: NCT03432364

Last Updated: 2023-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-29
• Study Completion Date: 2022-11-17

Brief Summary

This is a single-arm, multi-site, single-dose, Phase 1/2 study to assess ST-400 in 6 subjects with transfusion-dependent β-thalassemia (TDT) who are ≥18 and ≤40 years of age. ST-400 is a type of investigational therapy that consists of gene edited cells. ST-400 is composed of the patient's own blood stem cells which are genetically modified in the laboratory using Sangamo's zinc finger nuclease (ZFN) technology to disrupt a precise and specific sequence of the enhancer of the BCL11A gene (which normally suppresses fetal hemoglobin production in erythrocytes). This process is intended to boost fetal hemoglobin (HbF), which can substitute for reduced or absent adult (defective) hemoglobin. ST-400 is then infused back into the patient after receiving conditioning chemotherapy to make room for the new cells in the bone marrow, with the aim of producing new erythrocytes with increased amounts of HbF. The primary objective is to understand safety and tolerability of ST-400, and secondary objectives are to assess the effects on HbF levels and transfusion requirements.

Detailed Description

Once consented, study participants will progress through the following stages:

• Screening: in-person visit at the study site to confirm eligibility for proceeding
• Collection: autologous (self) blood stem cells are harvested at the study site, also known as apheresis
• Manufacturing of ST-400: no study participant activities expected
• Infusion: conditioning chemotherapy, followed by infusion of ST-400, occurs at the study site
• Follow-up: follow up at the study site to monitor for safety and effectiveness of the study

Conditions

Transfusion Dependent Beta-thalassemia

Keywords

Beta thalassemia; Beta-thalassemia; Thalassemia major; Cooley's anemia; ZFN mediated genome editing; zinc finger nuclease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ST-400 Investigational product

ST-400 Investigational product is composed of autologous CD34+ hematopoietic stem/progenitor cells that are genetically modified ex vivo at the erythroid-specific enhancer of the BCL11A gene

Group Type: EXPERIMENTAL

ST-400 Investigational product

Intervention Type: GENETIC

Single dose of ST-400 following chemotherapy conditioning with busulfan

Interventions

ST-400 Investigational product

Single dose of ST-400 following chemotherapy conditioning with busulfan

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

1. Informed Consent

2. Clinical diagnosis of TDT with ≥ 8 documented RBC transfusion events per year on an annualized basis in the 2-years prior to screening

3. Confirmed beta-thalassemia diagnosis by molecular genetic testing

4. Clinically stable and eligible to receive conditioning chemotherapy

5. Able and willing to use an effective method of contraception from the signing of the informed consent and for one year following ST-400 infusion.

Exclusion Criteria

1. Previous history of autologous or allogeneic blood stem cell transplantation or solid organ transplantation

2. Pregnant or breastfeeding female

3. Medical contraindication to mobilization, apheresis, or conditioning

4. Significant liver, lung, heart, or kidney dysfunction

5. Diagnosis of HIV or evidence of active HBV or HCV

6. History of significant bleeding disorder or uncontrolled seizures

7. History of active malignancy in past 5 years (non-melanoma skin cancer or cervical cancer in situ permitted) any history of hematologic malignancy, or family history of cancer predisposition syndrome without negative testing result in the study candidate.

8. Currently participating in another clinical trial using an investigational study medication, or recent participation in such a trial

9. Previous treatment with gene therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sangamo Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Sangamo Therapeutics, Inc.

Locations

University of California, Los Angeles

Los Angeles, California, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Dana-Farber Boston Children's Cancer and Blood Disorders Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

References

Brusson M, Miccio A. Genome editing approaches to beta-hemoglobinopathies. Prog Mol Biol Transl Sci. 2021;182:153-183. doi: 10.1016/bs.pmbts.2021.01.025. Epub 2021 Mar 1.

Reference Type: DERIVED

PMID: 34175041 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

ST-400-01

Identifier Type: -

Identifier Source: org_study_id