Clinical trial NCT03589833: Effectiveness and Safety of Yisaipu Combined With Tripterygium Wilfordii for Active RA
Official title: Effectiveness and Safety of Tumor Necrosis Factor Receptor Fusion Protein(Yisaipu) Combined With Tripterygium Wilfordii for Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Keywords: Rheumatoid Arthritis
Methotrexate
Tripterygium
TNF inhibitor
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2018-07-18
Enrollment: 504
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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

Primary outcomes:
measure: The American College of Rheumatology 50 (ACR50) response at 12 weeks
timeFrame: week 12
Secondary outcomes:
measure: The American College of Rheumatology 20/70 (ACR20/ACR70) response at 12 weeks
timeFrame: week 12
measure: The American College of Rheumatology 20/50/70 (ACR20/ACR50/ACR70) response at 24 weeks
timeFrame: week 24
measure: The Disease Activity Score-28 (DAS28) response at 24 weeks
timeFrame: week 24
measure: The European League Against Rheumatism (EULAR) response at 12 weeks
timeFrame: week 12
measure: Health Assessment Questionnaire without Didability Index (HAQ-DI) at 12 weeks
timeFrame: week 12
Other outcomes:
measure: The Incidence of adverse events during 24-week study
timeFrame: week 24
Locations:
city: Beijing
country: China
facility: Deptment of Rheumatology, Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Xuan Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: