Clinical Study on the Safety and Efficacy of BRL-101 in the Treatment of Sickle Cell Disease

NCT06287086 | Not Yet Recruiting

• 1 other identifier: 2024-BRL-101-SCD
• Study Type: interventional
• Target: 1
• Locations: 0 countries
• Sites: N/A

Brief 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)

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (3)

• 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.

  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

  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

  Within 12 Months After BRL-101 Infusion

Study Arms (1)

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.

Drug: BRL-101 autologous hematopoietic stem and progenitor cells injection

Interventions

BRL-101 autologous hematopoietic stem and progenitor cells injection DRUG

CD34 + autologous hematopoietic stem and progenitor cells edited at the BCL11A gene.

Also known as: BRL-101

BRL-101

Eligibility Criteria

• Age: 3 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Bioray Laboratories: lead
• Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College: collaborator

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Jun shi, PhD

  Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College

  STUDY CHAIR

Central Study Contacts

Jun shi, PhD

CONTACT

13752253515; shijun@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: February 29, 2024
• Study Start: June 14, 2024
• Primary Completion: August 20, 2025
• Study Completion (Estimated): June 10, 2026
• Last Updated: June 3, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share