Safety and Efficacy of UC-MSCs in Patients With Plaque Psoriasis

Study Overview
=================
Brief Summary
-----------------
This is a study in patients with moderate to severe chronic plaque psoriasis.All the participants will be randomized into three groups, high-dose UC-MSCs, low-dose UC-MSCs, or methotrexate group.This study is designed to prove that UC-MSCs is safe and effective.

Detailed Description
-----------------
Psoriasis is a chronic, incurable, immune-mediated dermatological disease, and it is considered that immune system dysregulation is the important cause of the disease.Umbilical cord derived mesenchymal stem cells (UC-MSCs) have be proven safe and effective for the treatment of various intractable autoimmune and inflammatory disorders because of their distinct immunomodulatory properties. Patients will be randomized into three groups.In one group patients will be treated with 1x10^6 cells/kg in 0,1,2,3,5,7 week, in the second group patients will be treated with 3x10^6 cells/kg in 0,1,2,3,5,7 week,in the third group patients will be treated with 5-25mg Methotrexate from 0 to 15 week In this study, researchers will determine the safety of UC-MSCs that a patient can tolerate without causing side effects. Moreover researchers will also be assess the efficacy and sustainability of UC-MSCs in 52 weeks.

Official Title
-----------------
A Randomized, Positive Controlled Trial That Assess the Safety And Efficacy of Umbilical Cord-Derived Mesenchymal Stem Cells in Moderate and Severe Plaque Psoriasis Patients

Conditions
-----------------
Moderate and Severe Plaque Psoriasis

Intervention / Treatment
-----------------
* Biological: Low-dose UC-MSCs
* Biological: High-dose UC-MSCs
* Drug: Methotrexate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients ≥18 years old with moderate-to-severe psoriasis. Diagnosis of plaque psoriasis at least 6 months before entering the study. Moderate-to-severe plaque psoriasis(PASI≥10，or BSA≥10% and DLQI score≥10). Failure after conventional therapy. No other treatment for psoriasis during the period of the trial. Willing and able to comply with all study requirements and provide informed consent. Exclusion Criteria: Other types of psoriasis,such as pustular, erythrodermic and guttate psoriasis). Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium). Ongoing use of other psoriasis treatments. Ever use of any biologic drug directly targeting IL-17,IL-23,TNFa etc. Active systemic infections during the last two weeks (exception: common cold) prior to initiation of the trial and any infections that reoccur on a regular basis. History of malignancy . Evidence of infection with HIV, hepatitis B or hepatitis C. Pregnant or lactating females, or willing to have a baby during the trial. Can not be traced on time.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Dose UC-MSCs<br>Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) 1 x 10^6 cells/kg in normal saline injection | Biological: Low-dose UC-MSCs<br>* Participants will receive 6 times UC-MSCs infusions (each time 1×10^6/kg). The first time to fourth time will be given once a week for successive 4 weeks（week 0,1,2,3）, then the last two times will be given once every two weeks（week 5,7）.<br>* Other names: regenskin;|
| Experimental: High-Dose UC-MSCs<br>Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) 3 x 10^6 cells/kg in normal saline injection | Biological: High-dose UC-MSCs<br>* Participants will receive 6 times UC-MSCs infusions (each time 3×10^6/kg). The first time to fourth time will be given once a week for successive 4 weeks（week 0,1,2,3）, then the last two times will be given once every two weeks（week 5,7）.<br>* Other names: regenskin;|
| Active Comparator: Methotrexate<br>5-25mg Methotrexate orally | Drug: Methotrexate<br>* Participants will be administered Methotrexate (each time 5-25mg) orally once a week for successive 16 weeks(week 0-15).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who have 75% or more reduction in [Psoriasis area-and-severity index score (PASI)] (PASI75) at week 20 | The proportion of subjects who have a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) at week 20 | Week 20 | 
| Proportion of subjects who achieve a score of 0 or 1 on a 5-point Physician's global assessment（PGA0/1) at week 20 | The proportion of subjects who achieve a score of 0（clear）or 1（almost clear）on a 5-point Physician's global assessment（PGA0/1) at week 20 | Week 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who have 90% or more reduction in [Psoriasis area-and-severity index score (PASI)] (PASI90) at week 20 | The proportion of subjects who have a reduction of 90% or more from baseline in the psoriasis area-and-severity index score (PASI 90) at week 20 | Week 20 | 
| Proportion of subjects who have 75% or more reduction in [Psoriasis area-and-severity index score (PASI)] (PASI75) at week 12,16,36,52 | The proportion of subjects who have a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) at week 12,16,36,52 | Week 12,16,36,52 | 
| Proportion of subjects who achieve a score of 0 or 1 on a 5-point Physician's global assessment（PGA0/1) at week 12,16,36,52 | The proportion of subjects who achieve a score of 0（clear）or 1（almost clear）on a 5-point Physician's global assessment（PGA0/1) at week 12,16,36,52 | Week 12,16,36,52 | 
| Frequency of Adverse Events and Serious Adverse Events | Frequency of all Adverse Events (AEs) and Serious Adverse Events (SAEs) that occur during the whole trial including the observational period (AEs and SAEs include but not limited to headaches, allergies, fever and so on | Week 0 through week 52 | 
| Proportion of subjects who experience psoriasis relapse | The proportion of subjects who experience a psoriasis relapse at any time until week 52. Psoriasis relapse is defined as loss of > 50% of the initial PASI improvement measured at week 7 | Week 8 though week 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
psoriasis, UC-MSCs