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

NCT03589833 | Completed Phase 4 DMC

• 1 other identifier: YISTAR
• Study Type: interventional
• Target: 504
• Locations: 1 country
• Sites: 1

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.

Conditions

Arthritis, Rheumatoid

Keywords

Rheumatoid Arthritis; Methotrexate; Tripterygium; TNF inhibitor

Outcome Measures

Primary Outcomes (1)

• 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.

  week 12

Secondary Outcomes (5)

• The American College of Rheumatology 20/70 (ACR20/ACR70) response at 12 weeks

  week 12

• The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks

  week 24

• The Disease Activity Score-28 (DAS28) response at 24 weeks

  week 24

• The European League Against Rheumatism (EULAR) response at 12 weeks

  week 12

• Health Assessment Questionnaire without Didability Index (HAQ-DI) at 12 weeks

  week 12

Other Outcomes (1)

• The Incidence of adverse events during 24-week study

  week 24

Study Arms (4)

MTX

PLACEBO COMPARATOR

Treated with oral methotrexate and two placebos.

Drug: Methotrexate

Tripterygium Wilfordii

PLACEBO COMPARATOR

Treated with oral Tripterygium Wilfordii and two placebos.

Drug: Tripterygium Wilfordii

Yisaipu + MTX

ACTIVE COMPARATOR

Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.

Drug: Methotrexate; Drug: Yisaipu

Yisaipu + Tripterygium Wilfordii

EXPERIMENTAL

Treated with subcutaneously injected Yisaipu, oral methotrexate and a placebo.

Drug: Tripterygium Wilfordii; Drug: Yisaipu

Interventions

Tripterygium Wilfordii DRUG

Oral Tripterygium Wilfordii 20mg thrice daily for 24 weeks.

Tripterygium Wilfordii; Yisaipu + Tripterygium Wilfordii

Methotrexate DRUG

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.

MTX; Yisaipu + MTX

Yisaipu DRUG

Yisaipu, a Tumor Necrosis Factor Receptor Fusion Protein, was subcutaneously injected at a dose of 50 mg once a week for 24 weeks.

Yisaipu + MTX; Yisaipu + Tripterygium Wilfordii

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Deptment of Rheumatology, Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Related Publications (1)

• Zhang X, Yang H, Zuo X, Wu L, Peng J, Li Z, Li H, Ji W, Zhang L, Li X, Dai L, Lu L, Yang N, Wei W, Shuai Z, Jiang Y, Liu Y, Lipsky PE, Chen H; YISTAR study group. Efficacy and safety of tripterygium wilfordii Hook F plus TNF inhibitor for active rheumatoid arthritis: A multicentre, randomized, double-blind, triple-dummy controlled trial. Clin Immunol. 2023 Oct;255:109749. doi: 10.1016/j.clim.2023.109749. Epub 2023 Aug 30.

  PMID: 37657525 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Xuan Zhang, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 5, 2018
• First Posted: July 18, 2018
• Study Start: May 14, 2019
• Primary Completion: March 20, 2022
• Study Completion: July 27, 2022
• Last Updated: October 25, 2022

Record last verified: 2022-10

Locations

CN (1)