Sickle Cell DiseaseNCT06287086
Clinical Study on the Safety and Efficacy of BRL-101 in the Treatment of Sickle Cell Disease
A study testing BRL-101 autologous hematopoietic stem and progenitor cells injection in people with Sickle Cell Disease, run by Bioray Laboratories.
Trial summary
This is a single center, non-randomized, open label, single-dose study in subjects with Sickle Cell Disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (BRL-101) Read more about this study
- Who is it for?
- Ages 3 to 35 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- BRL-101 autologous hematopoietic stem and progenitor cells injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- No sites listed yet
- Study dates
- 14 Jun 2024to 10 Jun 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 3 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects must meet all the following inclusion criteria to be eligible for enrolment into the study:
- Subject (or their legally authorized representative or guardian) will sign and date an informed consent form (ICF) and, where applicable, an assent form.
- Subjects 3 to 35 years of age, inclusive, on the date of informed consent.
- Clinically confirmed severe SCD, genotypes include: βS/βS, βS/β + or βS/β0. Severe SCD is defined as having at least 2 VOC events per year during the 2 years prior to screening and requiring appropriate supportive care, including a pain management program, HU therapy (if indicated).
- Karnofsky performance status of ≥80% for subjects ≥16 years of age. Lansky performance status of ≥80% for subjects <16 years of age (see Appendix 1 and 2).
- Eligible for autologous stem cell transplant as per investigator's judgment.
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- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures.
- Willing to participate in an additional long-term follow-up study after completion of this study (Study 2022-LTF-BRL-101).
- Subjects of childbearing potential must use effective contraception for at least 6 months after BRL-101 infusion during the study.
Who cannot join
- Subjects meeting any of the following criteria are not eligible for enrolment in the study:
- Known contraindications, intolerance, or hypersensitivity to hematopoietic stem cell mobilizers, busulfan injection, or dimethyl sulfoxide (DMSO) or study drug-related components.
- Eligible for allogeneic hematopoietic stem cell transplantation and have found HLA-identical donors.
- Prior allo-HSCT, gene therapy or gene editing therapy.
- Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
- HbF level >15.0%, irrespective of concomitant treatment with HbF inducing treatments such as HU.
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- Treatment with regular RBC transfusions that, in the opinion of the investigator, cannot be interrupted after engraftment.
- More than 10 unplanned hospitalizations or emergency department visits related to SCD in the 1 year before screening and the investigator considered this to be a significant chronic pain rather than an acute pain crisis.
- A history of clinically significant transcranial Doppler (TCD) test abnormalities or test abnormalities in the opinion of the investigator.
- History of untreated Moyamoya disease or presence of Moyamoya disease at Screening that in the opinion of the investigator puts the subjects at the risk of bleeding.
- the subject has participated in other clinical studies and used drugs within 3 months before screening.
- White blood cell count < 3 × 109/L and/or platelet count < 100 × 109/L not due to hypersplenism as judged by the investigator.
- INR > 1.5×ULN, APTT > 1.5×ULN.
- Creatinine > 1.5 × ULN or endogenous creatinine clearance < 60 ml/min (calculated according to the Cockcroft-Gault formula, see Appendix 3).
- ALT or AST> 3×ULN, or direct bilirubin value > 2.5×ULN.
- Severe iron overload with serum ferritin ≥ 5000 ng/ml, liver iron > 15 mg Fe/g dry weight (or liver MRIT2* < 1.4 ms or > 588 Hz), or heart MRI-T2* < 10 ms.
- LVEF < 50%.
- DLco < 50% predicted (corrected haemoglobin or/and alveolar volume) or forced vital capacity (FVC) (measured/predicted) < 60% (For children for whom DLco could not be determined), or abnormal blood gas analysis (for younger children with undetectable ventilatory function only).
- Hepatitis B virus surface antigen (HBsAg) positive or HBV-DNA positive; hepatitis C virus (HCV) antibody positive; human immunodeficiency virus (HIV) antibody positive; syphilis (TP) -specific antibody positive; Epstein-Barr virus EBV-DNA positive; cytomegalovirus CMV-DNA positive.
- History of a significant bleeding disorder.
- History or family history of malignancy or myeloproliferative disorder.
- Any prior or current cardiovascular system diseases, such as congestive heart failure, arrhythmia, myocardial disease, valvular heart disease or pulmonary hypertension; cirrhosis, liver fibrosis or active hepatitis; central nervous system diseases or mental illness.
- Presence of immune dysfunction or endocrine disorders, such as insulin-dependent diabetes mellitus, hyperthyroidism, or insufficiency.
- Pregnant or breastfeeding females.
- Any condition that, in the opinion of the investigator, would make participation in this clinical study inappropriate.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Clinical Study on the Safety and Efficacy of a Single Intravenous Dose of CRISPR/Cas9-Edited Autologous CD34+ Hematopoietic Stem/Progenitor Cells (BRL-101) in the Treatment of Sickle Cell Disease
This is a single center, non-randomized, open label, single-dose study in subjects with Sickle Cell Disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (BRL-101)
Read the detailed description
This clinical trial is a single-arm, single-dose, single center, open-label study without dose escalation. The primary objective is to explore the safety of the study drug in SCD. Myeloablative conditioning and administration for the remaining subjects can only be started after the first subject completes dosing and safety observation and assessment.
- Conditions
- Sickle Cell Disease
- Being tested
- BRL-101 autologous hematopoietic stem and progenitor cells injection
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BRL-101 autologous hematopoietic stem and progenitor cells injectionDrug
Also called BRL-101
CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A gene.
| Study group | Role | What they receive |
|---|---|---|
| BRL-101 | Experimental | BRL-101 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the BCL11A gene. Subjects will receive a single infusion of BRL-101. Receives: Drug: BRL-101 autologous hematopoietic stem and progenitor cells injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of stem cell engrafted subjects
Stem cell engraftment was defined as an absolute peripheral blood neutrophil count of ≥ 0.5 × 109/L for 3 consecutive days following BRL-101 intravenous infusion.
Measured: Within 42 Days After BRL-101 Infusion
Time to neutrophil engraftment
Defined as Day 1 of absolute peripheral blood neutrophil count ≥ 0.5 × 109/L for 3 consecutive days
Measured: Within 42 Days After BRL-101 Infusion
Frequency, severity, and relationship to BRL-101 of adverse events over 12 months following BRL-101 infusion..
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Measured: Within 12 Months After BRL-101 Infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study start14 Jun 2024 (estimated)
- Primary completion20 Aug 2025 (estimated)
- Study completion10 Jun 2026 (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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bioray Laboratories
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chinese Academy of Medical Sciences
- Responsible party
- Sponsor
- Investigators
- Jun shi, PhD, Study chair, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06287086
- Sponsor's protocol ID
- 2024-BRL-101-SCD
- Status last verified
- Jan 2024
- First submitted
- 23 Feb 2024
- Last updated
- 3 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- 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 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study on the Safety and Efficacy of a Single Intravenous Dose of CRISPR/Cas9-Edited Autologous CD34+ Hematopoietic Stem/Progenitor Cells (BRL-101) in the Treatment of Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT06287086
- Acronym / sponsor ID
- 2024-BRL-101-SCD
- Conditions
- Sickle Cell Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- Bioray LaboratoriesIndustry (pharma, biotech, devices)
- Collaborators
- Chinese Academy of Medical Sciences
- Study start
- 14 Jun 2024 (estimated)
- Primary completion
- 20 Aug 2025 (estimated)
- Study completion
- 10 Jun 2026 (estimated)
- First posted
- 29 Feb 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 is a single center, non-randomized, open label, single-dose study in subjects with Sickle Cell Disease (SCD). The study will evaluate the safety and efficacy of autologous CRISPR-Cas9 modified CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (BRL-101)
Detailed description
This clinical trial is a single-arm, single-dose, single center, open-label study without dose escalation. The primary objective is to explore the safety of the study drug in SCD. Myeloablative conditioning and administration for the remaining subjects can only be started after the first subject completes dosing and safety observation and assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BRL-101 | Experimental | Drug: BRL-101 autologous hematopoietic stem and progenitor cells injectionBRL-101 (autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the BCL11A gene. Subjects will receive a single infusion of BRL-101. |
Who may qualify
- Ages
- 3 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Subjects must meet all the following inclusion criteria to be eligible for enrolment into the study:
- Subject (or their legally authorized representative or guardian) will sign and date an informed consent form (ICF) and, where applicable, an assent form.
- Subjects 3 to 35 years of age, inclusive, on the date of informed consent.
- Clinically confirmed severe SCD, genotypes include: βS/βS, βS/β + or βS/β0. Severe SCD is defined as having at least 2 VOC events per year during the 2 years prior to screening and requiring appropriate supportive care, including a pain management program, HU therapy (if indicated).
- Karnofsky performance status of ≥80% for subjects ≥16 years of age. Lansky performance status of ≥80% for subjects <16 years of age (see Appendix 1 and 2).
Key exclusion criteria (25 listed)
- Subjects meeting any of the following criteria are not eligible for enrolment in the study:
- Known contraindications, intolerance, or hypersensitivity to hematopoietic stem cell mobilizers, busulfan injection, or dimethyl sulfoxide (DMSO) or study drug-related components.
- Eligible for allogeneic hematopoietic stem cell transplantation and have found HLA-identical donors.
- Prior allo-HSCT, gene therapy or gene editing therapy.
- Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator.
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 |
|---|---|---|
| BRL-101 autologous hematopoietic stem and progenitor cells injectionAlso: BRL-101CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A gene. | Drug | BRL-101 |
Primary outcome
Proportion of stem cell engrafted subjects
Time frame: Within 42 Days After BRL-101 Infusion
Stem cell engraftment was defined as an absolute peripheral blood neutrophil count of ≥ 0.5 × 109/L for 3 consecutive days following BRL-101 intravenous infusion.
Time to neutrophil engraftment
Time frame: Within 42 Days After BRL-101 Infusion
Defined as Day 1 of absolute peripheral blood neutrophil count ≥ 0.5 × 109/L for 3 consecutive days
Frequency, severity, and relationship to BRL-101 of adverse events over 12 months following BRL-101 infusion..
Time frame: Within 12 Months After BRL-101 Infusion
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 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. This study is not recruiting at the moment.
Jun shi, PhD study chair
Chinese Academy of Medical Sciences
Questions about this trial
What is this clinical trial studying?
A study testing BRL-101 autologous hematopoietic stem and progenitor cells injection in people with Sickle Cell Disease, run by Bioray Laboratories.
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 25 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: status not confirmed, as of the sponsor's last update on 3 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jun shi, PhD (13752253515, shijun@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of stem cell engrafted subjects (time frame: Within 42 Days After BRL-101 Infusion). The study lists 3 primary outcomes in all. 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 3 Jun 2024.