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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Completed; Phase 4

Conditions: Arthritis, Rheumatoid

Treatments: Drug: Methotrexate; Drug: Tripterygium Wilfordii; Drug: Yisaipu

Study type: Interventional

Funder types: Other

Identifiers

NCT03589833

YISTAR

Details and patient eligibility

About

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.

Full 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 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 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 :

1. ACR20, ACR50 and ACR70 response rates at 12 and 24 weeks.
2. DAS 28 (CRP) and DAS 28 (ESR) at 12 and 24 weeks.
3. EULAR response rates at 12 and 24 weeks.
4. Health assessment questionnaire (HAQ) at 12 and 24 weeks.
5. Patient assessment of arthritis pain at 12 and 24 weeks.
6. Patient and physician global assessment of arthritis at 12 and 24 weeks.

Enrollment: 504 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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504 participants in 4 patient groups, including a placebo group

MTX

Placebo Comparator group

Description:

Treated with oral methotrexate and two placebos.

Treatment:

Drug: Methotrexate

Tripterygium Wilfordii

Placebo Comparator group

Description:

Treated with oral Tripterygium Wilfordii and two placebos.

Treatment:

Drug: Tripterygium Wilfordii

Yisaipu + MTX

Active Comparator group

Description:

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

Treatment:

Drug: Methotrexate

Drug: Yisaipu

Yisaipu + Tripterygium Wilfordii

Experimental group

Description:

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

Treatment:

Drug: Tripterygium Wilfordii

Drug: Yisaipu