Tolerance, Pharmacokinetics and Preliminary Efficacy of T0001 in RA (Rheumatoid Arthritis)

Study Overview
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Brief Summary
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The purpose of this study is to assess the MTD, Pharmacokinetics and preliminary efficacy of T0001 in Rheumatoid Arthritis.

Official Title
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An Open, Dose Escalation, Multiple Dose Study to Assess Tolerance、Pharmacokinetics、Preliminary Efficacy of T0001 in RA (Rheumatoid Arthritis)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: T0001
* Drug: T0001
* Drug: T0001
* Drug: T0001
* Drug: Enbrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-45 years old; Diagnosed with active RA; DMARDs therapy must not be used for at least 28 days prior to baseline; If a patient has received NSAIDs，current NSAIDs therapy must have been at a stable dose for at least 28 days prior to baseline; Patient or patient's legal representative able to give written informed consent for participation in the trial. Exclusion Criteria: Acute or chronic infection, or history of active tuberculosis; History of diseases of central nervous system, cardiovascular system, kidney, liver ( specified liver function index), digestive system, respiratory system , metabolism system; Patients who have a high risk of infection (with a current infectious disease, a chronic infectious disease, a history of serious infectious disease); Patients who use 5 Unit doses tuberculin skin test are positive( 48-72 hour scleroma reading≥5mm); Patients who currently have, or who have a history of, malignancy; Patients who lack of understanding ,communication or collaboration, and can't comply with the protocols; Female patients who are breastfeeding or pregnant, who are of childbearing potential.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T0001<br> | Drug: T0001<br>* injection (SC) T0001 15mg weekly for 12 weeks<br>Drug: T0001<br>* injection (SC) T0001 30mg weekly for 12 weeks<br>Drug: T0001<br>* injection (SC) T0001 30mg every two weeks for 12 weeks<br>Drug: T0001<br>* injection (SC) T0001 50mg every two weeks for 12 weeks<br>|
| Active Comparator: Enbrel<br> | Drug: Enbrel<br>* injection (SC) enbrel 50mg twice a week for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerance Dose |  | 4 weeks | 
| Peak Plasma Concentration (Cmax) |  | 14 weeks | 
| Area under the plasma concentration versus time curve (AUC) |  | 14 weeks | 
| steady-state concentration（Css） |  | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology 20% (ACR20) Response | ACR20 responders are subjects with at least 20% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS) | 12 weeks | 
| American College of Rheumatology 50% (ACR50) Response | ACR50 responders are subjects with at least 50% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS) | 12 weeks | 
| American College of Rheumatology 70% (ACR70) Response | ACR70 responders are subjects with at least 70% improvement from Baseline for tender joint count (TJC), swollen joint count (SJC), and at least 3 of the 5 remaining core set measures: 1)Health Assessment Questionnaire-Disability Index (HAQ-DI), 2)C-reactive Protein (CRP), 3) Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS), 4) Patient's Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS), 5) Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGA-VAS) | 12 weeks |