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

Sponsor

Sangamo Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03432364

Collaborator

Sanofi (Industry)

Enrollment

Locations

Arm

55.1

Anticipated Duration (Months)

Patient Per Site

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

6 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 :

Mar 29, 2018

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 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

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

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Informed Consent
Clinical diagnosis of TDT with ≥ 8 documented RBC transfusion events per year on an annualized basis in the 2-years prior to screening
Confirmed beta-thalassemia diagnosis by molecular genetic testing
Clinically stable and eligible to receive conditioning chemotherapy
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:

Previous history of autologous or allogeneic blood stem cell transplantation or solid organ transplantation
Pregnant or breastfeeding female
Medical contraindication to mobilization, apheresis, or conditioning
Significant liver, lung, heart, or kidney dysfunction
Diagnosis of HIV or evidence of active HBV or HCV
History of significant bleeding disorder or uncontrolled seizures
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.
Currently participating in another clinical trial using an investigational study medication, or recent participation in such a trial
Previous treatment with gene therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095-1678
2	UCSF Benioff Children's Hospital Oakland	Oakland	California	United States	94609
3	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
4	Dana-Farber Boston Children's Cancer and Blood Disorders Center	Boston	Massachusetts	United States	02116
5	University of Minnesota	Minneapolis	Minnesota	United States	55455
6	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104