Sickle Cell DiseasePhase 1/2BAH243NCT06399107
Investigation Into the Use of BAH243 Lentiviral Vector for Gene Therapy in Treating Sickle Cell Disease
A Phase 1/2 study testing Drug Product is administered by IV infusion following myeloablative conditioning with busulfan in people with Sickle Cell Disease and Sickle-Cell Disease With Crisis, run by Essen Biotech at 1 site in China.
Trial summary
This study is an open-label, non-randomized, single-dose Phase 1/2 trial involving around 85 adult and pediatric participants aged between 2 and 50 years with sickle cell disease (SCD). It aims to assess the effectiveness of hematopoietic stem cell transplantation (HSCT) using BAH243 for SCD. Read more about this study
- Who is it for?
- Ages 2 to 90 years
- Conditions the study is for
- Sickle Cell Disease, Sickle-Cell Disease With Crisis
- What is being tested?
- Drug Product is administered by IV infusion following myeloablative conditioning with busulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2024to 28 Dec 2025
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 2 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Have a diagnosis of SCD, with either βS/βS, βS/β0, or βS/β+ genotype.
- Be ≥2 and ≤50 years of age at time of consent.
- Weigh a minimum of 6 kg.
- Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age).
- Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
- In the setting of appropriate supportive care measures (e.g., pain management plan), have experienced at least 4 protocol-defined VOEs in the 24 months prior to informed consent.
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- Have either experienced HU failure at any point in the past or must have intolerance to HU (intolerance is defined as the patient being unable to continue to take HU per PI judgment).
- Female and male subjects of childbearing potential agree to use 1 method of highly effective contraception from Screening to at least 6 months after drug product infusion.
- Provision of written informed consent for this study by subject, or as applicable, subject's parent(s)/legal guardian(s).
Who cannot join
- Subjects for whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically appropriate per PI judgment and a willing, human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available.
- Severe cerebral vasculopathy, defined by any history of overt ischemic or hemorrhagic stroke, a history of abnormal transcranial Doppler (TCD) or TCD imaging (TCDI) for subjects ≤ 16 years of age (e.g. TCD velocity >200 cm/sec) requiring ongoing chronic transfusions, a Screening TCD or TCDI velocity > 200 cm/sec (central read), a Screening MRA showing > 50% stenosis or occlusion in the circle of Willis (central read), or a Screening MRA showing the presence of Moyamoya (central read).
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1), active syphilis.
- Clinically significant, active bacterial, viral, fungal, or parasitic infection
- Advanced liver disease, such as
- clear evidence of liver cirrhosis, active hepatitis or significant fibrosis (based on MRI or liver biopsy)
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- liver iron concentration ≥15 mg/g unless liver biopsy shows no evidence of cirrhosis, active hepatitis or significant fibrosis
- Inadequate bone marrow function, as defined by an absolute neutrophil count of <1×10^9/L (<0.5×10^9/L for subjects on hydroxyurea treatment) or a platelet count <100×10^9/L.
- Any contraindications to the use of plerixafor during the mobilization of hematopoietic stem cells and any contraindications to the use of busulfan and any other medicinal products required during the myeloablative conditioning, including hypersensitivity to the active substances or to any of the excipients.
- Patients needing therapeutic anticoagulation treatment during the period of conditioning through platelet engraftment
- Unable to receive pRBC transfusion.
- Prior receipt of an allogeneic transplant.
- Prior receipt of gene therapy.
- Any prior or current malignancy or immunodeficiency disorder, except previously treated, non-life threatening, cured tumors such as squamous cell carcinoma of the skin.
- Immediate family member with a known or suspected Familial Cancer Syndrome.
- Female subject is breastfeeding, pregnant or will attempt to become pregnant from Screening to at least 6 months after drug product infusion.
- Any other condition that would render the subject ineligible for HSCT.
- Participation in another clinical study with an investigational drug within 30 days of screening.
- Presence of a chromosomal abnormality or genetic mutation that may put the subject at an increased risk of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) per Investigator's judgment.
- Presence of genetic mutations that result in the inactivation of 2 or more α-globin genes
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
District One Hospital
Beijing, Beijing Municipality, 086-373
SAMI XI, dr, +14012275001, SFM@districtonehospital.com
About this study
Official title: Lentiviral Vector Gene Therapy in Sickle Cell Disease Using Autologous CD34+ Hematopoietic Stem Cells Collected Via Apheresis and Modified With a Lentiviral Vector
This study is an open-label, non-randomized, single-dose Phase 1/2 trial involving around 85 adult and pediatric participants aged between 2 and 50 years with sickle cell disease (SCD). It aims to assess the effectiveness of hematopoietic stem cell transplantation (HSCT) using BAH243 for SCD.
Read the detailed description
Participants in this study will be involved for two years following their transplant. Those who join will also be invited to partake in a subsequent long-term follow-up study, which will continue to evaluate the safety and effectiveness of the treatment for an additional 13 years, culminating in a total of 15 years of observation post-infusion of the drug product. This clinical trial is structured as a single-arm, single-dose, single-center, open-label study without any dose escalation involved. Its main goal is to investigate the safety of the study drug in treating sickle cell disease (SCD). The treatment regimen, including myeloablative conditioning, will only commence for subsequent participants once the initial participant has successfully completed dosing and undergone a safety evaluation.
- Being tested
- Drug Product is administered by IV infusion following myeloablative conditioning with busulfan
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug Product is administered by IV infusion following myeloablative conditioning with busulfanGenetic
Also called BAH243
An autologous CD34+ cell-enriched population from patients with sickle cell disease (SCD), which includes hematopoietic stem cells (HSCs) that have been transduced with the BAH243 lentiviral vector (LVV) carrying the βA-T87Q-globin gene, is preserved in a cryopreservation solution.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Treatment (CD19/BCMA-CAR T cells, chemotherapy) | Experimental | Participants will be administered a one-time dose of the Drug Product, created using their own CD34+ hematopoietic stem cells which are gathered through plerixafor-induced mobilization and apheresis. These cells are then modified with the BAH243 lentiviral vector (LVV), which carries the human beta-A-T87Q globin gene.
Additionally, the same process of plerixafor mobilization and apheresis will be employed to collect rescue cells. Receives: Genetic: Drug Product is administered by IV infusion following myeloablative conditioning with busulfan |
What is being measured
The primary outcome is the main question the study is designed to answer.
VOE-CR
Proportion of subjects achieving complete resolution of VOEs between 6 months and 18 months after drug product infusion
Measured: 6-18 months post-transplant
Secondary outcomes (2)
sVOE-CR
Proportion of subjects achieving complete resolution of severe vaso-occlusive events, between 6 months and 18 months after drug product infusion
Measured: 6-18 months post-transplant
The proportion of subjects achieving Globin Response
Globin Response, defined as meeting the following criteria for a continuous period of at least 6 months after drug product infusion:
- Weighted average HbAT87Q percentage of non-transfused total Hb* ≥30% AND
- Weighted average non-transfused total Hb* increase of ≥3 g/dL compared to baseline total Hb* OR weighted average non-transfused total Hb* ≥10 g/dL
- non-transfused total Hb is the total g/dL of HbS + HbF + HbA2 + HbAT87Q
Measured: 6-24 months post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2024
- Study start1 Aug 2024
- Primary completion10 Nov 2025 (estimated)
- Study completion28 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies 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
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Essen Biotech
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06399107
- Sponsor's protocol ID
- ESBI202493
- Acronym
- BAH243
- Status last verified
- Nov 2024
- First submitted
- 29 Apr 2024
- Last updated
- 5 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lentiviral Vector Gene Therapy in Sickle Cell Disease Using Autologous CD34+ Hematopoietic Stem Cells Collected Via Apheresis and Modified With a Lentiviral Vector
- ClinicalTrials.gov ID
- NCT06399107
- Acronym / sponsor ID
- BAH243 / ESBI202493
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Essen BiotechUniversity, hospital or other
- Study start
- 1 Aug 2024 (actual)
- Primary completion
- 10 Nov 2025 (estimated)
- Study completion
- 28 Dec 2025 (estimated)
- First posted
- 3 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label, non-randomized, single-dose Phase 1/2 trial involving around 85 adult and pediatric participants aged between 2 and 50 years with sickle cell disease (SCD). It aims to assess the effectiveness of hematopoietic stem cell transplantation (HSCT) using BAH243 for SCD.
Detailed description
Participants in this study will be involved for two years following their transplant. Those who join will also be invited to partake in a subsequent long-term follow-up study, which will continue to evaluate the safety and effectiveness of the treatment for an additional 13 years, culminating in a total of 15 years of observation post-infusion of the drug product. This clinical trial is structured as a single-arm, single-dose, single-center, open-label study without any dose escalation involved. Its main goal is to investigate the safety of the study drug in treating sickle cell disease (SCD). The treatment regimen, including myeloablative conditioning, will only commence for subsequent participants once the initial participant has successfully completed dosing and undergone a safety evaluation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Treatment (CD19/BCMA-CAR T cells, chemotherapy) | Experimental | Genetic: Drug Product is administered by IV infusion following myeloablative conditioning with busulfanParticipants will be administered a one-time dose of the Drug Product, created using their own CD34+ hematopoietic stem cells which are gathered through plerixafor-induced mobilization and apheresis. These cells are then modified with the BAH243 lentiviral vector (LVV), which carries the human beta-A-T87Q globin gene. Additionally, the same process of plerixafor mobilization and apheresis will be employed to collect rescue cells. |
Who may qualify
- Ages
- 2 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Have a diagnosis of SCD, with either βS/βS, βS/β0, or βS/β+ genotype.
- Be ≥2 and ≤50 years of age at time of consent.
- Weigh a minimum of 6 kg.
- Have a Karnofsky performance status of ≥60 (≥16 years of age) or a Lansky performance status of ≥60 (<16 years of age).
- Be treated and followed for at least the past 24 months prior to Informed Consent in medical center(s) that maintained detailed records on sickle cell disease history.
Key exclusion criteria (20 listed)
- Subjects for whom allogeneic hematopoietic stem cell transplantation (allo-HSCT) is medically appropriate per PI judgment and a willing, human leukocyte antigen (HLA)-matched related hematopoietic stem cell donor is available.
- Severe cerebral vasculopathy, defined by any history of overt ischemic or hemorrhagic stroke, a history of abnormal transcranial Doppler (TCD) or TCD imaging (TCDI) for subjects ≤ 16 years of age (e.g. TCD velocity >200 cm/sec) requiring ongoing chronic transfusions, a Screening TCD or TCDI velocity > 200 cm/sec (central read), a Screening MRA showing > 50% stenosis or occlusion in the circle of Willis (central read), or a Screening MRA showing the presence of Moyamoya (central read).
- Positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2), hepatitis B, hepatitis C, human T-lymphotropic virus-1 (HTLV-1), active syphilis.
- Clinically significant, active bacterial, viral, fungal, or parasitic infection
- Advanced liver disease, such as
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 |
|---|---|---|
| Drug Product is administered by IV infusion following myeloablative conditioning with busulfanAlso: BAH243An autologous CD34+ cell-enriched population from patients with sickle cell disease (SCD), which includes hematopoietic stem cells (HSCs) that have been transduced with the BAH243 lentiviral vector (LVV) carrying the βA-T87Q-globin gene, is preserved in a cryopreservation solution. | Genetic | Experimental: Treatment (CD19/BCMA-CAR T cells, chemotherapy) |
Primary outcome
VOE-CR
Time frame: 6-18 months post-transplant
Proportion of subjects achieving complete resolution of VOEs between 6 months and 18 months after drug product infusion
2 secondary outcomes
sVOE-CR
Time frame: 6-18 months post-transplant
The proportion of subjects achieving Globin Response
Time frame: 6-24 months post-transplant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2024.
- 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.
1 site 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 Drug Product is administered by IV infusion following myeloablative conditioning with busulfan in people with Sickle Cell Disease and Sickle-Cell Disease With Crisis, run by Essen Biotech at 1 site in China.
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 9 inclusion and 20 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: looking for participants now, as of the sponsor's last update on 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rhoda M Smith, Phd (+12077706670, clinical-trials@essen-biotech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
VOE-CR (time frame: 6-18 months post-transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Nov 2024.