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Effectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA (YISTAR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03589833
Recruitment Status : Unknown
Verified July 2018 by Xuan Zhang, Peking Union Medical College Hospital.
Recruitment status was:  Recruiting
First Posted : July 18, 2018
Last Update Posted : July 19, 2018
Sponsor:
Information provided by (Responsible Party):
Xuan Zhang, Peking Union Medical College Hospital

Tracking Information
First Submitted Date  ICMJE July 5, 2018
First Posted Date  ICMJE July 18, 2018
Last Update Posted Date July 19, 2018
Estimated Study Start Date  ICMJE July 2018
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
ACR50 at 12w [ Time Frame: week 12 ]
The difference of ACR50 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
  • 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.
  • 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.
  • 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
    • 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 [ 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.
  • 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:
    • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
  • ACR20/70 at 12w [ Time Frame: week 12 ]
    The difference of ACR20 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 12.
  • ACR20/50/70 at 24w [ Time Frame: week 24 ]
    The difference of ACR20, ACR50 and ACR70 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX) at week 24.
  • DAS28 response at 24w [ Time Frame: week 24 ]
    The change in DAS score from baseline to week 24 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX).
  • EULAR response at 12w [ 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.
  • HAQ at 12w [ Time Frame: week 12 ]
    The change in HAQ score from baseline to week 12 between Arm 4 (Yisaipu + Tripterygium Wilfordii) and Arm 1 (MTX).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA
Official Title  ICMJE Effectiveness and Safety of Tumor Necrosis Factor Receptor Fusion Protein(Yisaipu) Combined With Tripterygium Wilfordii for Active Rheumatoid Arthritis
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:

  1. To compare the efficacy of YISAIPU plus T2w versus MTX monotherapy for the treatment of signs and symptoms of RA.
  2. To evaluate the safety of YISAIPU plus T2w in patients with RA for 24 weeks.

Design:

This is a Phase 2, 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:

  1. Methotrexate monotherapy
  2. T2w monotherapy
  3. YISAIPU plus methotrexate
  4. YISAIPU plus T2w

Escape:

On week 12, 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 :

  1. ACR20, ACR50 and ACR70 response rates at 4, 12 and 24 weeks.
  2. DAS 28 (CRP) and DAS 28 (ESR) at 4, 12 and 24 weeks.
  3. EULAR response rates at 4, 12 and 24 weeks.
  4. Health assessment questionnaire (HAQ) at 4, 12 and 24 weeks.
  5. Patient assessment of arthritis pain at 4, 12 and 24 weeks.
  6. Patient and physician global assessment of arthritis at 4, 12 and 24 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE
  • Drug: Tripterygium Wilfordii
    Oral Tripterygium Wilfordii 20mg thrice daily for 24 weeks.
  • Drug: Methotrexate
    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.
  • Drug: Yisaipu
    Yisaipu, a Tumor Necrosis Factor Receptor Fusion Protein, was subcutaneously injected at a dose of 50 mg once a week for 24 weeks.
Study Arms  ICMJE
  • Placebo Comparator: MTX
    Treated with oral methotrexate and two placebos.
    Intervention: Drug: Methotrexate
  • Placebo Comparator: Tripterygium Wilfordii
    Treated with oral Tripterygium Wilfordii and two placebos.
    Intervention: Drug: Tripterygium Wilfordii
  • Active Comparator: Yisaipu + MTX
    Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
    Interventions:
    • Drug: Methotrexate
    • Drug: Yisaipu
  • Experimental: Yisaipu + Tripterygium Wilfordii
    Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.
    Interventions:
    • Drug: Tripterygium Wilfordii
    • Drug: Yisaipu
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: July 17, 2018)
504
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18-65 years with informed consent
  • Fulfill the 2010 ACR/EULAR classification criteria for rheumatoid arthritis
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03589833
Other Study ID Numbers  ICMJE YISTAR
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Xuan Zhang, Peking Union Medical College Hospital
Study Sponsor  ICMJE Peking Union Medical College Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Xuan Zhang, MD Peking Union Medical College Hospital
PRS Account Peking Union Medical College Hospital
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP