Transfusion Dependent Beta-thalassemiaPhase 1/2NCT03432364
A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT)
A Phase 1/2 study testing ST-400 Investigational product in people with Transfusion Dependent Beta-thalassemia, run by Sangamo Therapeutics at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Transfusion Dependent Beta-thalassemia
- What is being tested?
- ST-400 Investigational product
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 6 sitesUnited States
- Study dates
- 29 Mar 2018to 17 Nov 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Dana-Farber Boston Children's Cancer and Blood Disorders Center
Boston, Massachusetts, 02116
University of California, Los Angeles
Los Angeles, California, 90095-1678
University of Minnesota
Minneapolis, Minnesota, 55455
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
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)
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.
Read the 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
- Conditions
- Transfusion Dependent Beta-thalassemia
- Being tested
- ST-400 Investigational product
- Keywords
- Beta thalassemia, Beta-thalassemia, Thalassemia major, Cooley's anemia, ZFN mediated genome editing, zinc finger nuclease
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ST-400 Investigational productGenetic
Single dose of ST-400 following chemotherapy conditioning with busulfan
| Study group | Role | What they receive |
|---|---|---|
| ST-400 Investigational product | Experimental | 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 Receives: Genetic: ST-400 Investigational product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 Weeks After the ST-400 Infusion
Safety and tolerability assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 weeks after the ST-400 infusion
Measured: Up to 156 weeks after the ST-400 infusion
Secondary outcomes (4)
Clinical Laboratory Measurement of Hemoglobin (Hb) Fractions (A and F in g/dL)
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]
Measured: Baseline, Weeks 26, 52, and 156 after ST-400 infusion
Clinical Laboratory Measurements of Percent (%) HbF
Change from baseline percent (%) HbF [Time Frame: Up to 156 weeks after ST-400 infusion]
Measured: Baseline, Weeks 26, 52, and 156 after ST-400 infusion
Annualized Frequency of Packed RBC Transfusions
Calculation of annualized frequency and volume of packed red blood cell (PRBC) transfusions after ST-400 infusion transfusion support in the 2 years prior to screening
Measured: From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion)
Annualized Volume (mL) of Packed RBC Transfusions
Historical baseline defined as transfusion support in the 2 years prior to screening.
Measured: From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2018
- Study start29 Mar 2018
- Primary completion17 Nov 2022
- Study completion17 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transfusion Dependent Beta-thalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sangamo Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Sangamo Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03432364
- Sponsor's protocol ID
- ST-400-01
- Status last verified
- Nov 2023
- First submitted
- 1 Feb 2018
- Last updated
- 14 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 34175041
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03432364
- Acronym / sponsor ID
- ST-400-01
- Conditions
- Transfusion Dependent Beta-thalassemia
- Keywords
- Beta thalassemia, Beta-thalassemia, Thalassemia major, Cooley's anemia, ZFN mediated genome editing, zinc finger nuclease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Sangamo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2018 (actual)
- Primary completion
- 17 Nov 2022 (actual)
- Study completion
- 17 Nov 2022 (actual)
- First posted
- 14 Feb 2018 (actual)
- Results
- Posted 13 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ST-400 Investigational product | Experimental | Genetic: ST-400 Investigational productST-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 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ST-400 Investigational productSingle dose of ST-400 following chemotherapy conditioning with busulfan | Genetic | ST-400 Investigational product |
Primary outcome
Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 Weeks After the ST-400 Infusion
Time frame: Up to 156 weeks after the ST-400 infusion
Safety and tolerability assessed by number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 weeks after the ST-400 infusion
4 secondary outcomes
Clinical Laboratory Measurement of Hemoglobin (Hb) Fractions (A and F in g/dL)
Time frame: Baseline, Weeks 26, 52, and 156 after ST-400 infusion
Clinical Laboratory Measurements of Percent (%) HbF
Time frame: Baseline, Weeks 26, 52, and 156 after ST-400 infusion
Annualized Frequency of Packed RBC Transfusions
Time frame: From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion)
Annualized Volume (mL) of Packed RBC Transfusions
Time frame: From Baseline (2 years prior to screening/consent), to ST-400 Infusion (Day 0), after hematopoietic reconstitution and up to 156 weeks (post ST-400 infusion)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34175041Brusson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Sangamo Therapeutics, Inc.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ST-400 Investigational product in people with Transfusion Dependent Beta-thalassemia, run by Sangamo Therapeutics at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 156 Weeks After the ST-400 Infusion (time frame: Up to 156 weeks after the ST-400 infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03432364, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2023.