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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03432364
Recruitment Status : Active, not recruiting
First Posted : February 14, 2018
Last Update Posted : May 13, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Sangamo Therapeutics

Tracking Information
First Submitted Date  ICMJE February 1, 2018
First Posted Date  ICMJE February 14, 2018
Last Update Posted Date May 13, 2020
Actual Study Start Date  ICMJE March 29, 2018
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Transfusion Dependent Beta-thalassemia
Intervention  ICMJE Genetic: ST-400 Investigational product
Single dose of ST-400 following chemotherapy conditioning with busulfan
Study Arms  ICMJE 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 * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2018)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03432364
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Sangamo Therapeutics
Study Sponsor  ICMJE Sangamo Therapeutics
Collaborators  ICMJE Sanofi
Investigators  ICMJE
Study Director: Medical Monitor Sangamo Therapeutics, Inc.
PRS Account Sangamo Therapeutics
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP