Hydroxytriptolide in Active Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of Hydroxytriptolide(LTS) in active rheumatoid arthritis patients with an inadequate response to methotrexate.

Detailed Description
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Investigate the efficacy of Hydroxytriptolide in active RA patients Investigate the safety of Hydroxytriptolide in active RA patients. Especially in female reproductive system. Population PK study.

Official Title
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A Radomized, Double-blind, and Placebo-controlled Multicenter Clinical Trial of Hydroxytriptolide, in Active Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: LTS 0.25mg
* Drug: LTS 0.5mg
* Drug: LTS 1.0mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 35-65 years old, female, postmenopausal, parous, nulliparous with no fertility requirements 1987 ACR Diagnostic criteria or 2009 ACR/EULAR Diagnostic criteria. X ray of Evaluable Joint in phase I/II/III, Joint Function in Phase I/II/III Active RA Continuously taking MTX for at least three months, ≥7.5mg/week. Before first study dose, keep in stable MTX dose for at least 4 weeks Keep in stable NSAIDs dose or low-dose glucocorticoids for at least 4 weeks before first study dose Using non-prohibited combination therapy, keep in stable dose for at least 7 days before first study dose Using DMARD should have appropriate withdrawal period: Withdrawal for 4 weeks: Sulfasalazine, Azathioprine, Chloroquine, *Hydroxychloroquine, Auranofin, Penicillamine, Traditional Chinese medicine preparation(TGP, Sinomenine) Withdrawal for 8 weeks: Leflunomide Withdrawal for 8 weeks: Intramuscular, intravenous, intra-articular injection glucocorticoids Women with fertility, negative in pregnancy test, and agreed to take contraceptive measures physical Voluntary informed consent Willing to follow the required regimen and schedule, follow-up examination Exclusion Criteria: Currently suffering or have suffered from other inflammatory joint diseases, such as mixed connective tissue disease, scleroderma, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome, bone arthritis, rheumatoid arthritis, gouty arthritis, diagnosis of arthritis before 16yrs With severe non-articular manifestations such as high fever, interstitial pneumonia, pleurisy, pericarditis, severe vasculitis, neuropathy, etc. The evaluable joint underwent the surgical treatment within 2 months Currently or recent have serious, or progression, or disease history not controled, including: liver, kidney, blood, gastrointestinal, endocrine, metabolic, respiratory, cardiovascular, nervous system diseases Currently or have malignancy, lymphoproliferative disease history Continuously use Tripterygium preparations for more than three months and have no effect History of using TNF-a inhibitors of biological agents.(Adalimumab, infliximab, etanercept) Severe or persistent infection within 3 months X-ray shows active pulmonary infection HBV, HCV, HIV, AIDS WBC<4.0×10^9/L, PLT<100×10^9/L, Hb<85g/L AST>2×ULN, ALT>2×ULN Cr>135umol/L Used oral contraceptive druds within 3 months Pregnancy test was positive or lactating patients or patients with birth preparation Have to use the prohibited drugs With clinical symptoms of a serious history of drug abuse or alcohol abuse History of any durg clinical trials within 3 months Allergy to tripterygium Other reasons depends by the investigator

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.25mg<br>LTS 0.25mg,qd MTX qw | Drug: LTS 0.25mg<br>* use LTS 0.25mg/d<br>* Other names: Hydroxytriptolide;|
| Active Comparator: 0.5mg<br>LTS 0.5mg, qd MTX qw | Drug: LTS 0.5mg<br>* use LTS 0.5mg/d<br>* Other names: Hydroxytriptolide;|
| Active Comparator: 1.0mg<br>LTS 1.0mg,qd MTX qw | Drug: LTS 1.0mg<br>* use LTS 1.0mg/d<br>* Other names: Hydroxytriptolide;|
| Placebo Comparator: Placebo<br>Placebo qd MTX qw | Drug: Placebo<br>* use placebo once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ACR 20 at 12 weeks and at 24 weeks |  | 12weeks, 24weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in DAS 28 at 12 weeks and at 24 weeks |  | 12weeks, 24weeks | 
| The proportion of patients reached ACR50 at 12 weeks and 24 weeks |  | 12weeks, 24weeks | 
| The proportion of patients reached ACR70 at 12weeks and 24weeks |  | 12weeks,24weeks | 
| Change from baseline in swollen joint count at 12 weeks and 24 weeks |  | 12weeks,24weeks | 
| Change from baseline in tender joint count at 12weeks and 24weeks |  | 12weeks,24weeks | 
| Change from baseline in the duration of morning stiffness at 12 weeks and 24 weeks |  | 12 weeks and 24 weeks | 
| Change from baseline in rest pain at 12 weeks and 24 weeks |  | 12weeks,24weeks | 
| Change from baseline in PtGA patient global assessment at 12 weeks and 24 weeks |  | 12 weeks and 24 weeks | 
| Change from baseline in PGA physician global assessment at 12 weeks and 24 weeks |  | 12 weeks and 24 weeks | 
| Change from baseline in HAQ health assessment questionnaire at 12 weeks and 24 weeks |  | 12 weeks, 24 weeks | 
| Change from baseline in CRP,ESR,RF,CCP at 12 weeks and 24 weeks |  | 12 weeks, 24 weeks | 
| Change from baseline in IgA, IgG, IgM at 12 weeks and 24 weeks |  | 12 weeks, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydroxytriptolide, Rheumatoid Arthritis, Methotrexate, T8, LTS