Clinical Study of BRL-101 in the Treatment of Sickle Cell Disease

NCT06287099 | Not Yet Recruiting

• 1 other identifier: 2023-BRL-101-SCD
• Study Type: interventional
• Target: 5
• 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-201 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

Autologous CD34+ hHSPCs modified with CRISPR-Cas9 at the BCL11A gene. Subjects will receive a single infusion of BRL-101.

Drug: BRL-101

Interventions

BRL-101 DRUG

Subjects will receive a single infusion of BRL-101.

Also known as: Autologous hematopoietic stem and progenitor cells injection

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:

• Fully understood this study and voluntarily signed the written informed consent form.
• Aged between 3 and 35 years.
• Be diagnosed with Sickle Cell Disease (SCD), with a genotype of βS/βS, βS/β+ or βS/β0.
• A Lansky/Karnofsky Performance Status (LPS) score of ≥80.
• Suitable for autologous hematopoietic stem cell transplantation.
• Have good compliance and are willing to adhere to visit schedules, trial protocols, laboratory tests, and other trial procedures.
• Agree to participating in long-term follow-up studies.
• Subjects of childbearing potential must use effective contraception for at least 6 months following cell reinfusion 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
• Nanfang Hospital, Southern Medical University: 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

• Xiaoqin Feng, PhD

  Nanfang Hospital, Southern Medical University

  STUDY CHAIR

Central Study Contacts

Xiaoqin Feng, PhD

CONTACT

020-61641921; fxq126126@126.com

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: April 20, 2024
• Primary Completion: October 20, 2025
• Study Completion (Estimated): May 10, 2026
• Last Updated: March 19, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share