Hydroxytriptolide in Active Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate (T8)

Shanghai Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: LTS 0.5mg; Drug: LTS 0.25mg; Drug: LTS 1.0mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02202395

LTS-201-P1.0

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 patients

Sex: Female

Ages: 35 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 4 patient groups, including a placebo group

0.25mg

Active Comparator group

Description:

LTS 0.25mg,qd MTX qw

Treatment:

Drug: LTS 0.25mg

0.5mg

Active Comparator group

Description:

LTS 0.5mg, qd MTX qw

Treatment:

Drug: LTS 0.5mg

1.0mg

Active Comparator group

Description:

LTS 1.0mg,qd MTX qw

Treatment:

Drug: LTS 1.0mg

Placebo

Placebo Comparator group

Description:

Placebo qd MTX qw

Treatment:

Drug: Placebo