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

• ClinicalTrials.gov Identifier: NCT03432364
• Recruitment Status: Completed
• First Posted: February 14, 2018
• Last Update Posted: February 1, 2023
• Sponsor: Sangamo Therapeutics
• Collaborator: Sanofi
• Information provided by (Responsible Party): Sangamo Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Transfusion Dependent Beta-thalassemia	Genetic: ST-400 Investigational product	Phase 1; Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Open-label, Single-arm Study to Assess the Safety, Tolerability, and Efficacy of ST-400 Autologous Hematopoietic Stem Cell Transplant for Treatment of Transfusion-Dependent Beta-thalassemia (TDT)
• Actual Study Start Date: March 29, 2018
• Actual Primary Completion Date: November 17, 2022
• Actual Study Completion Date: November 17, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Genetic: ST-400 Investigational product; Single dose of ST-400 following chemotherapy conditioning with busulfan

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability assessed by Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Primary Study Period. [ Time Frame: Up to 156 weeks after the ST-400 infusion ]

Secondary Outcome Measures :

1. Change from baseline clinical laboratory measurement of Hb fractions (A and F in g/dL). [ Time Frame: Up to 156 weeks after ST-400 infusion ]
2. Change from baseline in percent (%) HbF. [ Time Frame: Up to 156 weeks after ST-400 infusion ]
3. Change from baseline in annualized frequency of packed RBC transfusions [ Time Frame: Up to 156 weeks after ST-400 infusion ]
   Historical baseline defined as transfusion support in the 2 years prior to screening.
4. Change from baseline in annualized volume (mL) of packed RBC transfusions [ Time Frame: Up to 156 weeks after ST-400 infusion ]
   Historical baseline defined as transfusion support in the 2 years prior to screening.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

University of California, Los Angeles

Los Angeles, California, United States, 90095-1678

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States, 94609

United States, Georgia

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30322

United States, Massachusetts

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

Boston, Massachusetts, United States, 02116

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Sangamo Therapeutics

Sanofi

Investigators

• Study Director: Medical Monitor; Sangamo Therapeutics, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sangamo Therapeutics
• ClinicalTrials.gov Identifier: NCT03432364
• Other Study ID Numbers: ST-400-01
• First Posted: February 14, 2018
• Last Update Posted: February 1, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sangamo Therapeutics:

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

Additional relevant MeSH terms:

Thalassemia; beta-Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn