Safety and Efficacy of Expanded Allogeneic AD-MSCs in Patients With Moderate to Severe Psoriasis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of Adipose-derived Mesenchymal Stem Cells (AD-MSCs) with moderate to severe psoriasis. Any adverse events related to AD-MSCs infusion will be monitored. Safety is assessed using incidence of Adverse Events(AEs) and Serious Adverse Events (SAEs). Efficacy is assessed via the proportion of the improvement of PASI (Psoriasis Area and Severity Index), relapse rate in treatment period, changes in PASI score and BSA, as well as DLQI.

Detailed Description
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Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both. Numerous topical and systemic therapies are available for the treatment of psoriasis. Treatment modalities are chosen on the basis of disease severity, relevant comorbidities, patient preference. For moderate to severe psoriasis, phototherapy, systemic therapy and biologic immune modifying agents are recommended, but all of them have some drawbacks or limitations. Until now, no curative treatment is available. Therefore, it is important to find new treatment for psoriasis. Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can differentiate into bone, cartilage and adipose cells. Adipos-derived Mesenchymal Stem Cells(AD-MSCs) were isolated from fat tissues and were reported to treat moderate to severe psoriasis vulgaris and psoriasis arthritis successfully by case reports. For the mechanism of the disease, involvement of the immune system in psoriasis is now widely accepted. Mesenchymal stem cells (MSCs) are found to have the function of immunomodulation, migration to skin lesions, limitation of autoimmunity. Therefore, investigators supposed that the injection of AD-MSCs could be beneficial for treatment of moderate to severe psoriasis.

Official Title
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Safety and Efficacy of Expanded Allogeneic Adipose-derived Mesenchymal Stem Cells in Patients With Moderate to Severe Psoriasis

Conditions
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Psoriasis, Mesenchymal Stromal Cells, Drug Toxicity, Drug Effect

Intervention / Treatment
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* Biological: adipose-derived multipotent mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1．moderate to severe psoriasis vulgaris ( PASI > 10 or BSA >10% ) 2．18 to 65 years old 3．written/signed informed consent Exclusion Criteria: guttate psoriasis, inverse psoriasis or exclusively associated with the face Acute progressive psoriasis, and erythroderma tendency current (or within 1 year) pregnancy or lactation current significant anxiety or depression with the Self-rating Anxiety Scale (SAS) > 50 or the Self-rating Depression Scale (SDS) > 53, or with other psychiatric disorders With history of primary cardiovascular, respiratory, digestive, urinary, endocrinologic and hematologic diseases, which can't be controlled through ordinary treatments. Those who with malignant diseases, infections, electrolyte imbalance, acid-base disturbance. Patients with clinical test results listed below: abnormal serum calcium level ( Ca2+ > 2.9 mmol/L or < 2 mmol/L);AST or ALT 2 times more than normal upper limit; Creatinine and cystatin C more than normal upper limit; Hemoglobin elevates 20g/L more than normal upper limit,or hemoglobin reduction to anemia; Platelet count less than 75.0*10^9/L; White blood cell less than 3.0*10^9/L; Or any other abnormal laboratory test results, assessed by investigators, that are not suitable for this clinical study Patients with malignant tumors, or when they were enrolled with abnormal tumor markers or with other organ dysfunction allergy to anything else ever before; current registration in other clinical trials or participation within a month; topical treatments (i.e. corticosteroids or retinoic acid or Vitamin D analogs ) within 2 weeks; systemic therapy or phototherapy (ultraviolet radiation B,UVB) and psoralen combined with ultraviolet A (PUVA) within 4 weeks; biological therapy within 12 weeks; medical conditions assessed by investigators, that are not suitable for this clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AD-MSCs group<br>AD-MSCs（adipose-derived multipotent mesenchymal stem cells ） intravenous injection at a dose of 0.5 million cells/kg at week 0,week 4，week 8 with a duration for treatment for 12 weeks. | Biological: adipose-derived multipotent mesenchymal stem cells<br>* AD-MSCs(adipose-derived multipotent mesenchymal stem cells) were infused intravenously at a dose of 0.5 million cells/kg.<br>* Other names: AD-MSCs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) related to intervention | The proportion of the adverse events related to intervention in the treatment group. | 12 weeks (plus or minus 3 days) after treatment | 
| Incidence of serious adverse events (SAEs) related to intervention | The proportion of the serious adverse events related to intervention in the treatment group. | 12 weeks (plus or minus 3 days) after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement rate of PASI(Psoriasis Area and Severity Index) | The proportion of the improvement of PASI(Psoriasis Area and Severity Index) from baseline | 12 weeks (plus or minus 3 days) after treatment | 
| PASI(Psoriasis Area and Severity Index) | The improvement in PASI score from baseline after treatment | 12 weeks (plus or minus 3 days) after treatment | 
| PASI-50 | The proportion of patients who achieve at least 50% improvement in PASI score from baseline. | 12 weeks (plus or minus 3 days) after treatment | 
| PASI-75 | The proportion of patients who achieve at least 75% improvement in PASI score from baseline. | 12 weeks (plus or minus 3 days) after treatment | 
| Pruritus Scores on the Visual Analogue Scale | Pruritus Scores on the Visual Analogue Scale | 12 weeks (plus or minus 3 days) after treatment | 
| BSA | the Body Surface Area | 12 weeks (plus or minus 3 days) after treatment | 
| DLQI（Dermatology Life Quality Index） | the Dermatology Life Quality Index | 12 weeks (plus or minus 3 days) after treatment |