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

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)

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.

Study Overview

• Status: Completed
• Conditions: Transfusion Dependent Beta-thalassemia
• Intervention / Treatment: Genetic: ST-400 Investigational product

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 Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1678
      • University of California, Los Angeles
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Dana-Farber Boston Children's Cancer and Blood Disorders Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

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

Description

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

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: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 Weeks After the ST-400 Infusion	Safety and tolerability assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 weeks after the ST-400 infusion	Up to 156 weeks after the ST-400 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Laboratory Measurement of Hemoglobin (Hb) Fractions (A and F in g/dL)	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]	Baseline, Weeks 26, 52, and 156 after ST-400 infusion
Clinical Laboratory Measurements of Percent (%) HbF	Change from baseline percent (%) HbF [Time Frame: Up to 156 weeks after ST-400 infusion]	Baseline, Weeks 26, 52, and 156 after ST-400 infusion
Annualized Frequency of Packed RBC Transfusions	Calculation of annualized frequency and volume of packed red blood cell (PRBC) transfusions after ST-400 infusion transfusion support in the 2 years prior to screening	From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion)
Annualized Volume (mL) of Packed RBC Transfusions	Historical baseline defined as transfusion support in the 2 years prior to screening.	From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion)

Collaborators and Investigators

• Sponsor: Sangamo Therapeutics
• Collaborators: Sanofi
• Investigators: Study Director: Medical Monitor, Sangamo Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): November 17, 2022
• Study Completion (Actual): November 17, 2022

Study Registration Dates

• First Submitted: February 1, 2018
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (Actual): February 14, 2018

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Beta-thalassemia; Thalassemia major; Beta thalassemia; Cooley's anemia; ZFN mediated genome editing; zinc finger nuclease
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia
• Other Study ID Numbers: ST-400-01

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: Yes
• Studies a U.S. FDA-regulated device product: No