Rheumatoid Arthritis (RA)
Conditions
Keywords
Sertoli cells, Rheumatoid Arthritis (RA), intra-articular injection, hiSCs
Brief summary
This trial is a single-center, single-arm exploratory clinical study aimed at assessing the safety, tolerability, and preliminary efficacy of a single intra-articular injection of hiSCs for the treatment of rheumatoid arthritis.
Detailed description
This trial is a single-center, single-arm exploratory clinical study aimed at assessing the safety, tolerability, and preliminary efficacy of a single intra-articular injection of hiSCs for the treatment of rheumatoid arthritis. In this trial, participants who have given informed consent will be screened to determine their eligibility according to the inclusion and exclusion criteria. The study intervention consists of a single injection of hiSCs, and the primary endpoint will be assessed during the 24-week follow-up visit after the cell injection.
Interventions
BIOLOGICALhiSCs
hiSCs are derived from human induced pluripotent stem cells and exhibit immunomodulatory properties.
Sponsors
Shanghai Changzheng Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following inclusion criteria 1. Voluntarily sign the informed consent; 2. Male or female aged 18-65 years (inclusive) at the time of signing the informed consent; 3. Diagnosis of RA for ≥3 months according to the ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria at the screening visit; 4. At the screening visit, presence of recurrent swelling and pain in at least one knee, with a WOMAC pain score ≥4, synovial inflammation confirmed by joint ultrasound, and no significant improvement following 3 months of anti-RA treatment (including prior use of MTX standard therapy, biologics, or small molecule targeted drugs); 5. Subjects must have received csDMARD therapy for ≥3 months, with a stable dose for ≥4 weeks prior to screening; 6. Background treatment with stable-dose MTX standard therapy, biologics, or small molecule targeted drugs, either alone or in combination, is permitted; 7. The following csDMARDs, either alone or in combination, are permitted as background treatment, provided the dose has been stable for ≥4 weeks prior to screening: oral or IV MTX (10-25 mg/week; for subjects intolerant to doses ≥10 mg/week, the dose should be ≥7.5 mg/week), SAS (≤3 g/day), hydroxychloroquine (≤400 mg/day), and LEF (≤20 mg/day); 8. Stable-dose NSAIDs are permitted, provided the dose has remained stable for ≥2 weeks prior to screening; 9. All females of childbearing potential must have a negative blood pregnancy test within 7 days prior to treatment initiation and must not be breastfeeding. Females not of childbearing potential may be exempt from the pregnancy test and contraception. All enrolled patients (regardless of gender) must use at least one highly effective method of contraception, including adequate barrier methods, throughout the study duration; 10. Subjects must be in good overall health, able to ambulate independently (excluding those requiring a wheelchair, walker, or crutches); 11. Willingness and ability to adhere to scheduled visits, treatment regimens, laboratory tests, and other study-related procedures.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC | At 12 weeks after the injection of hiSCs | The change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (range: 0-240 cm; including pain, stiffness, and physical function subscales) for the target knee, as assessed by the subject, with higher scores indicating greater symptom severity and worse physical function |
| GSUS | At 12 weeks after the injection of hiSCs | The change from baseline in Gray-scale ultrasound (GSUS) (range: 0-12; including suprapatellar, medial, lateral, and posterior planes) for the target knee, as assessed by musculoskeletal ultrasound, with higher scores indicating more severe synovitis |
| PDUS | At 12 weeks after the injection of hiSCs | The change from baseline in Power Doppler Ultrasound Synovitis (PDUS) score (range: 0-15; including suprapatellar, infrapatellar, medial, lateral, and posterior compartments) for the target knee, as assessed by power Doppler ultrasound, with higher scores indicating more severe synovitis |
| TEAEs and SAEs | Within 12 weeks after the injection of hiSCs | The incidence of TEAEs and SAEs related to the study intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HAQ-DI | At Weeks 2, 4, 8, 12, and 24 | Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI; ACR Core Set measure; range 0-3, higher scores indicate worse functional status) |
| Patient-reported pain intensity (VAS） | At Weeks 2, 4, 8, 12, and 24 | Change from baseline in patient-reported pain intensity (Visual Analog Scale \[VAS\]; ACR Core Set measure; 0-100 mm, higher scores indicate severe pain) |
| Patient-reported global disease activity (VAS) | At Weeks 2, 4, 8, 12, and 24 | Change from baseline in patient-reported global disease activity (VAS; ACR Core Set measure; 0-100 mm, higher scores indicate worse status) |
| Physician-evaluated global disease activity (VAS) | At Weeks 2, 4, 8, 12, and 24 | Change from baseline in physician-evaluated global disease activity (VAS; ACR Core Set measure; 0-100 mm, higher scores indicate worse status) |
| Acute-phase reactant | At Weeks 2, 4, 8, 12, and 24 | Change from baseline in acute-phase reactant (C-reactive protein \[CRP; high-sensitivity assay; 0-10 mg/L\] or erythrocyte sedimentation rate \[ESR; 0-15 mm/h\]; ACR Core Set measure; higher values indicate worse inflammation) |
| DAS28 (CRP or ESR) score of <2.6 and <3.2 | At Weeks 2, 4, 8, 12, and 24 | The proportion of subjects achieving a DAS28 (CRP or ESR) score of \<2.6 and \<3.2 |
| DAS28 (CRP or ESR) | At Weeks 2, 4, 8, 12, and 24 | The change from baseline in Disease Activity Score 28 (DAS28) using C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), with higher scores indicating greater disease activity |
| SDAI score of ≤3.3 | At Weeks 2, 4, 8, 12, and 24 | The proportion of subjects achieving Simplified Disease Activity Index (SDAI) remission (score ≤3.3; total score range: 0-86), with lower scores indicating better disease control |
| SDAI | At Weeks 2, 4, 8, 12, and 24 | The change from baseline in Simplified Disease Activity Index (SDAI)score（total score range: 0-86), with lower scores indicating better disease control |
| CDAI score of ≤2.8 | At Weeks 2, 4, 8, 12, and 24 | The proportion of subjects achieving Clinical Disease Activity Index (CDAI) remission (score ≤ 2.8; total score range: 0-76), with lower scores indicating better disease control |
| VAS | At Weeks 2, 4, 8, 12, and 24 | The change from baseline in Visual Analog Scale (VAS) pain score (range: 0-100 mm) for the target knee, as assessed by the subject, with higher scores indicating greater symptom severity and worse physical function |
| WOMAC | At Weeks 2, 4, 8, and 24 | The change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (range: 0-240 cm; including pain, stiffness, and physical function subscales) for the target knee, as assessed by the subject, with higher scores indicating greater symptom severity and worse physical function |
| KOOS | At Weeks 2, 4, 8, 12, and 24 | The change from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) (range: 0-100; including Pain, Symptoms, Activities of Daily Living, Sport/Recreation, and Quality of Life subscales), as assessed by the subject, with higher scores indicating better function and fewer symptoms |
| WORMS | At 12 weeks after the injection of hiSCs | The change from baseline in Whole-Organ Magnetic Resonance Imaging Score (WORMS) (assessing ：cartilage morphology \[0-6 per subregion\], bone marrow lesions \[0-3 per subregion\], meniscal pathology \[0-4 per meniscus\], subchondral cysts \[0-3 per subregion\], osteophytes \[0-7 per subregion\], bone attrition \[0-3 per subregion\], synovitis/effusion \[0-3\], ligament abnormalities \[0-1 per ligament\], periarticular cysts \[0-3\], and loose bodies \[0-3\]), as assessed by MRI, with higher scores indicating more severe structural damage |
| MOAKS | At 12 weeks after the injection of hiSCs | The change from baseline in the MRI Osteoarthritis Knee Score (MOAKS) (assessing: cartilage damage \[0-3 per subregion\], bone marrow lesions \[0-3 per subregion\], osteophytes \[0-3 per subregion\], meniscal pathology \[0-3 per region, location；0-1 per region, morphology\], synovitis/effusion \[0-3\], ligament/tendon abnormalities \[0-1 per ligament/tendon\], and periarticular features \[0-1\]), as assessed by MRI, with higher scores indicating more severe structural damage |
| BLOKS | At 12 weeks after the injection of hiSCs | The change from baseline in the Boston-Leeds Osteoarthritis Knee Score (BLOKS) (assessing: cartilage morphology \[0-3 per region\], bone marrow lesions \[0-3 per region\], osteophytes \[0-3 per region\], meniscal pathology \[0-3 per region, location；0-1 per region, morphology\], synovitis/effusion \[0-3\], ligament abnormalities \[0-1 per ligament\], and periarticular features \[0-1\]), as assessed by MRI, with higher scores indicating more severe structural damage |
| Synovial thickness | At 12 weeks after the injection of hiSCs | The change from baseline in synovial thickness (mm), as assessed by MRI, with increased values indicating greater synovial inflammation |
| Synovial blood flow | At 12 weeks after the injection of hiSCs | The change from baseline in synovial blood flow (measured in mL/min/100g tissue), as assessed by MRI, with increased values indicating greater vascularity |
| Joint effusion volume | At 12 weeks after the injection of hiSCs | The change from baseline in joint effusion volume(mL), as assessed by MRI, with increased values indicating greater effusion severity |
| GSUS | At Weeks 2, 4, 8, and 24 | The change from baseline in Gray-scale ultrasound (GSUS) (range: 0-12; including suprapatellar, medial, lateral, and posterior planes) for the target knee, as assessed by musculoskeletal ultrasound, with higher scores indicating more severe synovitis |
| PDUS | At Weeks 2, 4, 8, and 24 | The change from baseline in Power Doppler Ultrasound Synovitis (PDUS) score (range: 0-15; including suprapatellar, infrapatellar, medial, lateral, and posterior compartments) for the target knee, as assessed by power Doppler ultrasound, with higher scores indicating more severe synovitis |
| CDAI | At Weeks 2, 4, 8, 12, and 24 | The change from baseline in Clinical Disease Activity Index (CDAI)score (total score range: 0-76), with lower scores indicating better disease control |
| ROM | At Weeks 2, 4, 8, 12, and 24 | The change from baseline in the range of motion (ROM) for the target knee, as assessed by a goniometer, with greater improvement indicating better physical function |
| ACR20, ACR50, ACR70 | At Weeks 2, 4, 8, 12, and 24 | The proportion of subjects who achieved ACR20, ACR50, and ACR70(American College of Rheumatology 20%/50%/70% improvement) |
| TJC | At Weeks 2, 4, 8, 12, and 24 | Change from baseline in 68-joint tender joint count (TJC; American College of Rheumatology \[ACR\] Core Set measure; range 0-68, higher scores indicate worse disease activity) |
| SJC | At Weeks 2, 4, 8, 12, and 24 | Change from baseline in 66-joint swollen joint count (SJC; ACR Core Set measure; range 0-66, higher scores indicate worse disease activity) |
Countries
China
Contacts
CONTACTHuji Xu, Ph.D, MD
PRINCIPAL_INVESTIGATORHuji Xu, Ph.D, MD
Shanghai Changzheng Hospital
Outcome results
None listed