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

Primary Purpose

Transfusion Dependent Beta-thalassemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ST-400 Investigational product

About this trial

This is an interventional treatment trial for Transfusion Dependent Beta-thalassemia focused on measuring Beta thalassemia, Beta-thalassemia, Thalassemia major, Cooley's anemia, ZFN mediated genome editing, zinc finger nuclease

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesDoes not accept 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

Sites / Locations

University of California, Los Angeles
UCSF Benioff Children's Hospital Oakland
Children's Healthcare of Atlanta
Dana-Farber Boston Children's Cancer and Blood Disorders Center
University of Minnesota
Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ST-400 Investigational product

Arm Description

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

Outcomes

Primary Outcome Measures

Safety and tolerability assessed by Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) during the Primary Study Period.

Secondary Outcome Measures

Change from baseline clinical laboratory measurement of Hb fractions (A and F in g/dL).

Change from baseline in percent (%) HbF.

Change from baseline in annualized frequency of packed RBC transfusions

Historical baseline defined as transfusion support in the 2 years prior to screening.

Change from baseline in annualized volume (mL) of packed RBC transfusions

Historical baseline defined as transfusion support in the 2 years prior to screening.

Full Information

NCT ID

NCT03432364

First Posted

February 1, 2018

Last Updated

January 31, 2023

Sponsor

Sangamo Therapeutics

Collaborators

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT03432364

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)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

March 29, 2018 (Actual)

Primary Completion Date

November 17, 2022 (Actual)

Study Completion Date

November 17, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sangamo Therapeutics

Collaborators

Sanofi

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Transfusion Dependent Beta-thalassemia

Keywords

Beta thalassemia, Beta-thalassemia, Thalassemia major, Cooley's anemia, ZFN mediated genome editing, zinc finger nuclease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ST-400 Investigational product

Arm Type

Experimental

Arm Description

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 Type

Genetic

Intervention Name(s)

ST-400 Investigational product

Intervention Description

Single dose of ST-400 following chemotherapy conditioning with busulfan

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

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

Title

Change from baseline in percent (%) HbF.

Time Frame

Up to 156 weeks after ST-400 infusion

Title

Change from baseline in annualized frequency of packed RBC transfusions

Description

Historical baseline defined as transfusion support in the 2 years prior to screening.

Time Frame

Up to 156 weeks after ST-400 infusion

Title

Change from baseline in annualized volume (mL) of packed RBC transfusions

Description

Historical baseline defined as transfusion support in the 2 years prior to screening.

Time Frame

Up to 156 weeks after ST-400 infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Monitor

Organizational Affiliation

Sangamo Therapeutics, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

University of California, Los Angeles

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095-1678

Country

United States

Facility Name

UCSF Benioff Children's Hospital Oakland

City

Oakland

State/Province

California

ZIP/Postal Code

94609

Country

United States

Facility Name

Children's Healthcare of Atlanta

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Dana-Farber Boston Children's Cancer and Blood Disorders Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02116

Country

United States

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455

Country

United States

Facility Name

Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34175041

Citation

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.

Results Reference

derived

Learn more about this trial

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

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