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

Tracking Information

• First Submitted Date: February 1, 2018
• First Posted Date: February 14, 2018
• Last Update Posted Date: February 1, 2023
• Actual Study Start Date: March 29, 2018
• Actual Primary Completion Date: November 17, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 31, 2019): 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 ]
• Original Primary Outcome Measures (submitted: February 7, 2018): Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive ST-400 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 156 weeks after the ST-400 infusion ]

Current Secondary Outcome Measures (submitted: May 5, 2020)

• 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 ]
• Change from baseline in percent (%) HbF. [ Time Frame: Up to 156 weeks after ST-400 infusion ]
• 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.
• 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.

Original Secondary Outcome Measures (submitted: February 7, 2018)

• 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 ]
• Change from baseline percent (%) HbF [ Time Frame: Up to 156 weeks after ST-400 infusion ]
• Change from baseline in annualized frequency of packed red blood cell (PRBC) transfusions after ST-400 infusion as compared to historical baseline [ Time Frame: Up to 156 weeks after ST-400 infusion ]
  Historical baseline defined as transfusion support in the 2 years prior to screening
• Change from baseline in annualized volume (mL) of packed red blood cell (PRBC) transfusions after ST-400 infusion as compared to historical baseline [ Time Frame: Up to 156 weeks after ST-400 infusion ]
  Historical baseline defined as transfusion support in the 2 years prior to screening

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Transfusion Dependent Beta-thalassemia

Intervention

Genetic: ST-400 Investigational product

Single dose of ST-400 following chemotherapy conditioning with busulfan

Study Arms

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

Intervention: Genetic: ST-400 Investigational product

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 26, 2023): 5
• Original Estimated Enrollment (submitted: February 7, 2018): 6
• Actual Study Completion Date: November 17, 2022
• Actual Primary Completion Date: November 17, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03432364
• Other Study ID Numbers: ST-400-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sangamo Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Sangamo Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Sanofi

Investigators

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

• PRS Account: Sangamo Therapeutics
• Verification Date: January 2023