Back to resultsEffectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA (YISTAR)
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Tripterygium Wilfordii
Methotrexate
Yisaipu
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Rheumatoid Arthritis, Methotrexate, Tripterygium, TNF inhibitor
Eligibility Criteria
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
Sites / Locations
- Deptment of Rheumatology, Peking Union Medical College Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Placebo Comparator
Placebo Comparator
Active Comparator
Experimental
Arm Label
MTX
Tripterygium Wilfordii
Yisaipu + MTX
Yisaipu + Tripterygium Wilfordii
Arm Description
Treated with oral methotrexate and two placebos.
Treated with oral Tripterygium Wilfordii and two placebos.
Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
Outcomes
Primary Outcome Measures
The American College of Rheumatology 50 (ACR50) response at 12 weeks
The difference of ACR50 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
Secondary Outcome Measures
The American College of Rheumatology 20/70 (ACR20/ACR70) response at 12 weeks
The difference of ACR20 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks
The difference of ACR20, ACR50 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 24.
The Disease Activity Score-28 (DAS28) response at 24 weeks
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
TJC28: The number of tender joints (0-28).
SJC28: The number of swollen joints (0-28).
CRP: The C-Reactive Protein level (in mg/l).
GH: The patient global health assessment (from 0=best to 100=worst).
The 28 joint: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees.
The European League Against Rheumatism (EULAR) response at 12 weeks
The difference of proportions of patients meeting EULAR response between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
Health Assessment Questionnaire without Didability Index (HAQ-DI) at 12 weeks
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:
from 0 to 1: mild difficulties to moderate disability,
from 1 to 2: disability moderate to severe,
from 2 to 3: severe to very severe disability.
The mean score is recorded as the result.
Full Information
NCT ID
NCT03589833
First Posted
July 5, 2018
Last Updated
October 23, 2022
Sponsor
Peking Union Medical College Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03589833
Brief Title
Effectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA
Acronym
YISTAR
Official Title
Effectiveness and Safety of Tumor Necrosis Factor Receptor Fusion Protein(Yisaipu) Combined With Tripterygium Wilfordii for Active Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
May 14, 2019 (Actual)
Primary Completion Date
March 20, 2022 (Actual)
Study Completion Date
July 27, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this 24-week, multi-center, randomized, double-blind study, the investigators will evaluate the efficacy and safety profile of subcutaneously injected Yisaipu, a Tumor Necrosis Factor Receptor Fusion Protein, combined with oral Tripterygium Wilfordii for patients with active rheumatoid arthritis.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
Rheumatoid Arthritis, Methotrexate, Tripterygium, TNF inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
504 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MTX
Arm Type
Placebo Comparator
Arm Description
Treated with oral methotrexate and two placebos.
Arm Title
Tripterygium Wilfordii
Arm Type
Placebo Comparator
Arm Description
Treated with oral Tripterygium Wilfordii and two placebos.
Arm Title
Yisaipu + MTX
Arm Type
Active Comparator
Arm Description
Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
Arm Title
Yisaipu + Tripterygium Wilfordii
Arm Type
Experimental
Arm Description
Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
Intervention Type
Drug
Intervention Name(s)
Tripterygium Wilfordii
Intervention Description
Oral Tripterygium Wilfordii 20mg thrice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Yisaipu
Intervention Description
Yisaipu, a Tumor Necrosis Factor Receptor Fusion Protein, was subcutaneously injected at a dose of 50 mg once a week for 24 weeks.
Primary Outcome Measure Information:
Title
The American College of Rheumatology 50 (ACR50) response at 12 weeks
Description
The difference of ACR50 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
Time Frame
week 12
Secondary Outcome Measure Information:
Title
The American College of Rheumatology 20/70 (ACR20/ACR70) response at 12 weeks
Description
The difference of ACR20 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
Time Frame
week 12
Title
The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks
Description
The difference of ACR20, ACR50 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 24.
Time Frame
week 24
Title
The Disease Activity Score-28 (DAS28) response at 24 weeks
Description
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
TJC28: The number of tender joints (0-28).
SJC28: The number of swollen joints (0-28).
CRP: The C-Reactive Protein level (in mg/l).
GH: The patient global health assessment (from 0=best to 100=worst).
The 28 joint: shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and the knees.
Time Frame
week 24
Title
The European League Against Rheumatism (EULAR) response at 12 weeks
Description
The difference of proportions of patients meeting EULAR response between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
Time Frame
week 12
Title
Health Assessment Questionnaire without Didability Index (HAQ-DI) at 12 weeks
Description
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:
from 0 to 1: mild difficulties to moderate disability,
from 1 to 2: disability moderate to severe,
from 2 to 3: severe to very severe disability.
The mean score is recorded as the result.
Time Frame
week 12
Other Pre-specified Outcome Measures:
Title
The Incidence of adverse events during 24-week study
Description
Incidence of adverse events and sever adverse events (SAE), including hospitalized or Treatment-emergent adverse events, during 24-week study.
Time Frame
week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xuan Zhang, MD
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Deptment of Rheumatology, Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100032
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Effectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA
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