- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03589833
Effectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA (YISTAR)
Effectiveness and Safety of Tumor Necrosis Factor Receptor Fusion Protein(Yisaipu) Combined With Tripterygium Wilfordii for Active Rheumatoid Arthritis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study evaluates the efficacy and safety of YISAIPU plus Tripterygium wilfordii (T2w) for the treatment of RA patients. YISAIPU is a recombinant human tumor necrosis factor receptor fusion protein, and tripterygium wilfordii is a chloroform/methanol extract of Tripterygium wilfordii Hook F.
Objectives:
- To compare the efficacy of YISAIPU plus T2w versus MTX monotherapy for the treatment of signs and symptoms of RA.
- To evaluate the safety of YISAIPU plus T2w in patients with RA for 24 weeks.
Design:
This is a randomized, 24-week, double-blind, parallel group study, and 506 patients with active RA will be randomized in a 1:1:1:1 ratio to one of the following four parallel treatment arms:
- Methotrexate monotherapy
- T2w monotherapy
- YISAIPU plus methotrexate
- YISAIPU plus T2w
Escape:
On week 13, all participants with inadequate response, defined as a <30% improvement of swollen and tender joint counts from baseline, will switch to YISAIPU plus T2w treatment throughout the study.
Endpoints :
- ACR20, ACR50 and ACR70 response rates at 12 and 24 weeks.
- DAS 28 (CRP) and DAS 28 (ESR) at 12 and 24 weeks.
- EULAR response rates at 12 and 24 weeks.
- Health assessment questionnaire (HAQ) at 12 and 24 weeks.
- Patient assessment of arthritis pain at 12 and 24 weeks.
- Patient and physician global assessment of arthritis at 12 and 24 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100032
- Deptment of Rheumatology, Peking Union Medical College Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18-65 years with informed consent
- Diagnosis of rheumatoid arthritis (according to 2010 ACR/EULAR classification criteria)
- Disease duration > 6 weeks
- Swollen joint (SJC)≥4 and tender joint count(TJC)≥4
- ESR >28 mm/hr or C-reactive protein > 1.5 ULN
- Positive RF or anti-CCP antibody on screening
- Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA
- No evidence of active or latent or inadequately treated Mycobacterium tuberculosis infection
Exclusion Criteria:
- Pregnant, lactating or further fertility requirements
- Previously received any biologic agents.
- Recently (<12 weeks) received methotrexate, leflunomide, salazosulfapyridine, azathioprine, cyclosporine, mycophenolate mofetil or Tripterygium Wilfordii.
- Active or chronic infection, including HIV, HCV, HBV, tuberculosis.
- History of any other rheumatic autoimmune disease
- History of any lymphoproliferative disorder
- Malignancy or history of malignancy.
- Abnormal laboratory tests, including: Hemoglobin <8.5 g/dL, White blood cell count <3.5 x 109/L, Platelet count <100 x 109/L, AST/ALT >1.5 ULN, and serum creatine > 1.5 mg/dL.
- Severe, progressive, or uncontrolled cardiac, pulmonary, renal, hepatic, gastrointestinal, hematologic, metabolic, endocrine or neurologic disease
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: MTX
Treated with oral methotrexate and two placebos.
|
Oral methotrexate 7.5-15mg per week for 24 weeks.
The starting dose was 7.5mg per week, then increased to 15mg (max 0.3mg/Kg) per week in 4 weeks.
Folic acid at the dose of 5 mg per week were applied to all participants.
|
Placebo Comparator: Tripterygium Wilfordii
Treated with oral Tripterygium Wilfordii and two placebos.
|
Oral Tripterygium Wilfordii 20mg thrice daily for 24 weeks.
|
Active Comparator: Yisaipu + MTX
Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
|
Oral methotrexate 7.5-15mg per week for 24 weeks.
The starting dose was 7.5mg per week, then increased to 15mg (max 0.3mg/Kg) per week in 4 weeks.
Folic acid at the dose of 5 mg per week were applied to all participants.
Yisaipu, a Tumor Necrosis Factor Receptor Fusion Protein, was subcutaneously injected at a dose of 50 mg once a week for 24 weeks.
|
Experimental: Yisaipu + Tripterygium Wilfordii
Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
|
Oral Tripterygium Wilfordii 20mg thrice daily for 24 weeks.
Yisaipu, a Tumor Necrosis Factor Receptor Fusion Protein, was subcutaneously injected at a dose of 50 mg once a week for 24 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The American College of Rheumatology 50 (ACR50) response at 12 weeks
Time Frame: week 12
|
The difference of ACR50 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
|
week 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The American College of Rheumatology 20/70 (ACR20/ACR70) response at 12 weeks
Time Frame: week 12
|
The difference of ACR20 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
|
week 12
|
The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks
Time Frame: week 24
|
The difference of ACR20, ACR50 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 24.
|
week 24
|
The Disease Activity Score-28 (DAS28) response at 24 weeks
Time Frame: week 24
|
The change in DAS28 score from baseline to week 24 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX). DAS28 = 0.56*SQRT(TJC28) + 0.28*SQRT(SJC28) + 0.36*ln(CRP + 1) + 0.014*GH + 0.96
The 28 joint: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees. |
week 24
|
The European League Against Rheumatism (EULAR) response at 12 weeks
Time Frame: week 12
|
The difference of proportions of patients meeting EULAR response between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
|
week 12
|
Health Assessment Questionnaire without Didability Index (HAQ-DI) at 12 weeks
Time Frame: week 12
|
The change in HAQ-DI score from baseline to week 12 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX). HAQ-DI is an index measuring the quality of life related to health, which includes 20 questions in terms of three categories:
The mean score is recorded as the result. |
week 12
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Incidence of adverse events during 24-week study
Time Frame: week 24
|
Incidence of adverse events and sever adverse events (SAE), including hospitalized or Treatment-emergent adverse events, during 24-week study.
|
week 24
|
Collaborators and Investigators
Investigators
- Principal Investigator: Xuan Zhang, MD, Peking Union Medical College Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Methotrexate
Other Study ID Numbers
- YISTAR
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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