Clinical trial NCT02202395: Hydroxytriptolide in Active Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate
Official title: A Radomized, Double-blind, and Placebo-controlled Multicenter Clinical Trial of Hydroxytriptolide, in Active Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Hydroxytriptolide
Rheumatoid Arthritis
Methotrexate
T8
LTS
Lead sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
Sponsor class: INDUSTRY
First posted: 2014-07-29
Enrollment: 120
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 1. Investigate the efficacy of Hydroxytriptolide in active RA patients
2. Investigate the safety of Hydroxytriptolide in active RA patients. Especially in female reproductive system.
3. Population PK study.

Eligibility criteria: 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:

1. 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
2. With severe non-articular manifestations such as high fever, interstitial pneumonia, pleurisy, pericarditis, severe vasculitis, neuropathy, etc.
3. The evaluable joint underwent the surgical treatment within 2 months
4. Currently or recent have serious, or progression, or disease history not controled, including: liver, kidney, blood, gastrointestinal, endocrine, metabolic, respiratory, cardiovascular, nervous system diseases
5. Currently or have malignancy, lymphoproliferative disease history
6. Continuously use Tripterygium preparations for more than three months and have no effect
7. History of using TNF-a inhibitors of biological agents.(Adalimumab, infliximab, etanercept)
8. Severe or persistent infection within 3 months
9. X-ray shows active pulmonary infection
10. HBV, HCV, HIV, AIDS
11. WBC\<4.0×10\^9/L, PLT\<100×10\^9/L, Hb\<85g/L
12. AST\>2×ULN, ALT\>2×ULN
13. Cr\>135umol/L
14. Used oral contraceptive druds within 3 months
15. Pregnancy test was positive or lactating patients or patients with birth preparation
16. Have to use the prohibited drugs
17. With clinical symptoms of a serious history of drug abuse or alcohol abuse
18. History of any durg clinical trials within 3 months
19. Allergy to tripterygium
20. Other reasons depends by the investigator

Primary outcomes:
measure: Change from baseline in ACR 20 at 12 weeks and at 24 weeks
timeFrame: 12weeks, 24weeks
Secondary outcomes:
measure: Change from baseline in DAS 28 at 12 weeks and at 24 weeks
timeFrame: 12weeks, 24weeks
measure: The proportion of patients reached ACR50 at 12 weeks and 24 weeks
timeFrame: 12weeks, 24weeks
measure: The proportion of patients reached ACR70 at 12weeks and 24weeks
timeFrame: 12weeks,24weeks
measure: Change from baseline in swollen joint count at 12 weeks and 24 weeks
timeFrame: 12weeks,24weeks
measure: Change from baseline in tender joint count at 12weeks and 24weeks
timeFrame: 12weeks,24weeks
measure: Change from baseline in the duration of morning stiffness at 12 weeks and 24 weeks
timeFrame: 12 weeks and 24 weeks
measure: Change from baseline in rest pain at 12 weeks and 24 weeks
timeFrame: 12weeks,24weeks
measure: Change from baseline in PtGA patient global assessment at 12 weeks and 24 weeks
timeFrame: 12 weeks and 24 weeks
measure: Change from baseline in PGA physician global assessment at 12 weeks and 24 weeks
timeFrame: 12 weeks and 24 weeks
measure: Change from baseline in HAQ health assessment questionnaire at 12 weeks and 24 weeks
timeFrame: 12 weeks, 24 weeks
measure: Change from baseline in CRP,ESR,RF,CCP at 12 weeks and 24 weeks
timeFrame: 12 weeks, 24 weeks
measure: Change from baseline in IgA, IgG, IgM at 12 weeks and 24 weeks
timeFrame: 12 weeks, 24 weeks
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Shanghai
country: China
facility: Changzheng Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee
state: Shanghai
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee
name: Chunde Bao, MD
role: PRINCIPAL_INVESTIGATOR
References: