BC-U001 is an allogeneic fresh human umbilical cord-derived mesenchymal stem cell product, which showed therapeutic potential for rheumatoid arthritis(RA) based on its anti-inflammatory, immunomodulatory and tissue repair activities. The primary objective of this open-label, non-randomized, dose-escalation study is to evaluate the safety and tolerability of a single intravenous infusion of BC-U001 for RA patients using a 3+3 design.
This study will enroll RA patients who still remained moderate-to-high disease activity after conventional synthetic DMARDs (csDMARDs) therapy. All participants are informed about the study procedures and potential risks and are required to provide written informed consent prior to study begin. A 3+3 dose escalation design will be implemented. Three ascending dose cohorts (3 participants/cohort) will be treated successively to identify the maxium tolerated dose (MTD) and/or a recommended dose for phase II study. Dose escalation will be terminated if the dose-limiting toxicities (DLT) are observed in 2 participants during the 28-day follow-up within cohort. DLT was defined as any ≥grade 3 non-hematological toxicity or grade 4 hemtological toxicity according to CTCAE v5.0, which was related to the investigational product determined by investigator.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
The participants are intravenously administered a single infusion of hUC-MSC at 0.5x10\^6 cells/kg body weight, 1.0x10\^6 cells/kg body weight, 1.5x10\^6 cells/kg body weight for low-dose cohort, medium-dose cohort and high-dose cohort respectively.
Peking Union Medical College Hospital (Dongdan campus)
Beijing, Beijing Municipality, China
Number and frequency of adverse events (AEs)
Adverse events are assessed by CTCAE 5.0 up to 28±3 days. The flexible change of ±3 days is set for the convenience of patients. Day 1 refers to the day the participant accept BC-U001 infusion.
Time frame: Up to day 28±3
Changes of vital signs from 1 hour after infusion to day 28±3
Time frame: Up to day 28±3
Changes of complete blood count (CBC) from day 1 to day 28±3
Time frame: Up to day 28±3
Changes of blood biochemical from day 1 to day 28±3
Time frame: Up to day 28±3
Changes of coagulation function from day 1 to day 28±3
Time frame: Up to day 28±3
Routine urine analysis
Time frame: Up to day 28±3
Urine pregnancy test (female only)
Time frame: 28±3 days
Cardiac rate measured by twelve-lead electrocardiogram
Time frame: Up to day 28±3
Percentage of participants achieving ACR20
Time frame: Up to day 28±3
Percentage of participants achieving ACR50
Time frame: Up to day 28±3
Percentage of participants achieving ACR70
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Time frame: Up to day 28±3
Change from baseline of the disease activity score based on DAS28-CRP
Time frame: Up to day 28±3
Change from baseline of the disease activity score based on DAS28-ESR
Time frame: Up to day 28±3
EULAR response
Time frame: Up to day 28±3
Change from baseline of the health assessment questionnaire(HAQ) score
Time frame: Up to day 28±3
Change from baseline of the simplified disease activity index (SDAI) score
Time frame: Up to day 28±3
Change from baseline of the clinical disease activity index (CDAI) score
Time frame: Up to day 28±3
Change from baseline of TNF-α level
Time frame: Up to day 28±3
Change from baseline of IL-6 level
Time frame: Up to day 28±3