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

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ClinicalTrials.gov Identifier: NCT03432364
Recruitment Status : Recruiting
First Posted : February 14, 2018
Last Update Posted : May 28, 2018
Sponsor:
Collaborator:
Bioverativ Therapeutics Inc.
Information provided by (Responsible Party):
Sangamo Therapeutics

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, and is done without the use of integrating viral vectors. 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
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)
Estimated Study Start Date : May 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2022


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




Primary Outcome Measures :
  1. 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 ]

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 percent (%) HbF [ Time Frame: Up to 156 weeks after ST-400 infusion ]
  3. 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

  4. 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



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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 double barrier method of contraception for at least 3 months prior to ST-400 infusion and through 6 months post-transplant

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 apheresis
  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)
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03432364


Contacts
Contact: Medical Monitor 510-307-7266 clinicaltrials@sangamo.com

Locations
United States, California
UCSF Benioff Children's Hospital Oakland Recruiting
Oakland, California, United States, 94609
Contact: Marci Moriarty, BSN, RN    510-428-3885 ext 5396    mmoriarty@mail.cho.org   
Principal Investigator: Mark Walters, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Angela Smith, M.D., M.S.    612-625-7253    smith719@umn.edu   
Contact: Jennifer Braun, R.N., BSN    612-625-0084    danie659@umn.edu   
Principal Investigator: Angela Smith, M.D., M.S.         
Sponsors and Collaborators
Sangamo Therapeutics
Bioverativ Therapeutics Inc.
Investigators
Study Director: Medical Monitor Sangamo Therapeutics, Inc.

Responsible Party: Sangamo Therapeutics
ClinicalTrials.gov Identifier: NCT03432364     History of Changes
Other Study ID Numbers: ST-400-01
First Posted: February 14, 2018    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: May 2018
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