Safety and Efficacy of Adipose-Derived Regenerative Cells (ADRCs) for Improving Hand Dysfunction in Systemic Sclerosis

Safety and Efficacy of Autologous Adipose-Derived Regenerative Cells (ADRCs) for Improving Hand Dysfunction in Systemic Sclerosis: A Prospective, Randomized, Multicenter Superiority Trial

This prospective, randomized, blinded, multicenter clinical study aims to evaluate the safety and efficacy of autologous adipose-derived regenerative cells (ADRCs) in improving hand dysfunction in patients with systemic sclerosis (SSc). The study plans to enroll 48 eligible patients, randomly assigned to two groups. The experimental group will receive ADRCs, prepared from the Celution system, which is injected into specific sites on each finger of both hands. The control group will receive standard care according to established treatment guidelines. The primary endpoint is the change from baseline in the Cochin Hand Function Scale (CHFS) score at 24 weeks. Secondary endpoints include assessments of skin thickness, Raynaud phenomenon, hand strength, quality of life, pain, and other measures at various time points. Safety and device performance will be monitored throughout the study. This investigation seeks to explore a new potential therapeutic direction for managing hand dysfunction in systemic sclerosis.

Systemic sclerosis (SSc) often preferentially affects the hands, leading to skin thickening, limited mobility, pain, and even digital ulcers, severely impairing hand function and quality of life in patients. This prospective, randomized, multicenter, superiority-designed clinical study aims to evaluate the safety and efficacy of autologous adipose-derived regenerative cells (ADRCs) prepared using the Celution 800/GP System and the Celution 805 for improving hand dysfunction in patients with systemic sclerosis.

The study plans to enroll 48 eligible patients, randomly assigned to two groups. For the ADRCs group, at least 180 mL of autologous adipose tissue was obtained via liposuction. The Celution 800/GP system and Celution 805 were used to wash, separate, and enrich the ADRCs. These were then adjusted to a volume of 10 mL using Lactated Ringer's solution (divided into 10 syringes of 1 mL each) and injected into specific sites on each finger of both hands (both sides of the metacarpophalangeal joint of the thumb and both sides of the proximal interphalangeal joints of the other fingers). The control group received standard treatment guided by the "Diagnosis and Treatment Guidelines for Systemic Sclerosis." Patients were randomly assigned to the two groups in a 1:1 ratio. Participants were followed up multiple times within 4 weeks, 12 weeks, and 24 weeks post-procedure.

The primary endpoint was the change from baseline in the Cochin Hand Function Scale (CHFS) score at 24 weeks. Secondary endpoints included changes from baseline in the CHFS score at 4 and 12 weeks; the modified Rodnan skin score at 4, 12, and 24 weeks; Raynaud's Condition Score; Kapandji score; hand grip strength/pinch strength; Systemic Sclerosis Health Assessment Questionnaire (SHAQ) score; pain Visual Analogue Scale (VAS) score; and digital ulcer clinical assessment scale score at the respective timepoints. Additionally, changes from baseline in hand skin ultrasound examination and nailfold capillaroscopy results at 24 weeks were assessed. Performance evaluation of the Celution800/GP system and Celution805, monitoring of safety indicators, and device deficiencies were also included.

Statistical analysis followed standard principles using SAS software (version 9.4). Efficacy analyses were performed using data from both the Full Analysis Set and the Per-Protocol Set, while safety analyses used the Safety Analysis Set.

This study focuses on the safety and efficacy of autologous ADRCs in treating hand dysfunction in systemic sclerosis, offering a new direction for improving hand dysfunction.

Inclusion Criteria:

1. Age 18-70 years old (inclusive), gender not restricted;
2. According to the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) systemic sclerosis (SSc) diagnostic criteria, diagnosed as diffuse cutaneous type or localized cutaneous type;
3. Thickened hand skin, modified Rodnan skin score ≥ 8 points and ≤ 35 points;
4. Cochin Hand Function Scale (CHFS) ≥ 20 (total score 90), with or without skin ulcers;
5. Capable of safely undergoing liposuction to obtain sufficient adipose tissue (the preferred fat extraction sites are the abdomen, followed by the lateral abdomen, inner and outer thighs, posterior thighs, and anterior thighs; multiple sites can be selected for liposuction to obtain sufficient adipose tissue);
6. Voluntary participation in this clinical trial and signing the informed consent form by the subject.

Exclusion Criteria:

1. Subject's body mass index (BMI) < 17 kg/m^2;
2. Hand skin lesions are in the atrophic stage, and the investigator determines that they are not suitable for hand drug injection;
3. Any finger contracture or injection site ulcer that makes it unsafe to complete the injection;
4. Any proximal to distal interphalangeal joint amputation of any finger, or amputation of more than one finger;
5. Concurrent other rheumatic immune diseases, such as RA, SLE, dermatomyositis, etc. (existing rheumatic immune diseases that do not affect the safety and efficacy evaluation of the hand and do not affect the safety of the hand and efficacy evaluation, excluding Sjögren's syndrome);
6. Active infectious diseases or patients who have used antibiotics within 3 months before the screening visit due to active infectious diseases;
7. Patients with unstable systemic sclerosis who have received cell therapy before the screening visit;
8. Patients who have undergone chemotherapy or resection of malignant cancer within 5 years before the screening visit;
9. Abnormal tumor markers detected during the screening period, and the investigator determines that there is a tumor risk;
10. Patients who have received CD20 monoclonal antibody treatment within 1 year before the screening visit, or have used other biologic drugs or taken small molecule targeted drugs within 3 months before the screening visit (excluding those who have maintained a stable dose of ≥ 3 months at the time of enrollment for systemic sclerosis treatment);
11. Have received hand cell injection therapy before, or are intolerant to cell therapy, or have received systemic cell injection therapy within 6 months before the screening visit;
12. Patients with positive human immunodeficiency virus antibody (anti-HIV-Ab) test results, active syphilis, active hepatitis C (HCV-RNA positive, and hepatitis C antibody positive), hepatitis B (HBsAg positive and HBV-DNA positive) during the screening period;
13. There is evidence indicating that the subject currently has possible safety-related diseases in the digestive system, urinary system, cardiovascular system, hematological system, nervous system, mental state, and metabolism, such as poorly controlled diabetes, poorly controlled hypertension, etc.;
14. Any of the following laboratory test results during the screening period: ① Abnormal blood routine: hemoglobin < 80 g/L; white blood cell count < 3.0 × 10^9/L; absolute neutrophil count < 1.2 × 10^9/L; platelet count < 100 × 10^9/L; ② Abnormal liver and kidney function: aspartate transaminase (AST), alanine aminotransferase (ALT), activated partial thromboplastin time (APTT) prolonged > 1.5 times the upper limit of the reference value; ③ Coagulation dysfunction: prothrombin time (PT) and partial thromboplastin time (APTT) prolonged > 1.8 times the upper limit of the reference value, or international normalized ratio (INR) > 2;
15. Allergic to any component of human albumin, anesthetic drugs, or human adipose-derived mesenchymal stem cell injection solution, or the investigator determines that the subject is not suitable for enrollment due to a severe allergy history;
16. Patients whose screening visit is within 3 months before the general anesthesia surgery planned during the study period;
17. Patients who have participated in other clinical studies within 3 months before the screening visit, or are currently participating in other clinical studies;
18. Pregnant women, lactating women, those with positive pregnancy test results, or those who do not agree to use effective contraceptive measures during the study period and within 6 months after the trial;
19. Patients judged by the investigator to be unsuitable to participate in this study.