| Eligibility |
Inclusion Criteria:
Subjects must meet all the following inclusion criteria to be eligible for enrolment into
the study:
1. Subject (or their legally authorized representative or guardian) will sign and date an
informed consent form (ICF) and, where applicable, an assent form.
2. Subjects 3 to 35 years of age, inclusive, on the date of informed consent.
3. Clinically confirmed severe SCD, genotypes include: ßS/ßS, ßS/ß + or ßS/ß0. 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).
4. 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).
5. Eligible for autologous stem cell transplant as per investigator's judgment.
6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
contraceptive guidelines, and other study procedures.
7. Willing to participate in an additional long-term follow-up study after completion of
this study (Study 2022-LTF-BRL-101).
8. Subjects of childbearing potential must use effective contraception for at least 6
months after BRL-101 infusion during the study.
Exclusion Criteria
Subjects meeting any of the following criteria are not eligible for enrolment in the study:
1. Known contraindications, intolerance, or hypersensitivity to hematopoietic stem cell
mobilizers, busulfan injection, or dimethyl sulfoxide (DMSO) or study drug-related
components.
2. Eligible for allogeneic hematopoietic stem cell transplantation and have found
HLA-identical donors.
3. Prior allo-HSCT, gene therapy or gene editing therapy.
4. Clinically significant and active bacterial, viral, fungal, or parasitic infection as
determined by the investigator.
5. HbF level >15.0%, irrespective of concomitant treatment with HbF inducing treatments
such as HU.
6. Treatment with regular RBC transfusions that, in the opinion of the investigator,
cannot be interrupted after engraftment.
7. 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.
8. A history of clinically significant transcranial Doppler (TCD) test abnormalities or
test abnormalities in the opinion of the investigator.
9. 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.
10. the subject has participated in other clinical studies and used drugs within 3 months
before screening.
11. White blood cell count < 3 × 109/L and/or platelet count < 100 × 109/L not due to
hypersplenism as judged by the investigator.
12. INR > 1.5×ULN, APTT > 1.5×ULN.
13. Creatinine > 1.5 × ULN or endogenous creatinine clearance < 60 ml/min (calculated
according to the Cockcroft-Gault formula, see Appendix 3).
14. ALT or AST> 3×ULN, or direct bilirubin value > 2.5×ULN.
15. 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.
16. LVEF < 50%.
17. 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).
18. 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.
19. History of a significant bleeding disorder.
20. History or family history of malignancy or myeloproliferative disorder.
21. 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.
22. Presence of immune dysfunction or endocrine disorders, such as insulin-dependent
diabetes mellitus, hyperthyroidism, or insufficiency.
23. Pregnant or breastfeeding females.
24. Any condition that, in the opinion of the investigator, would make participation in
this clinical study inappropriate.
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