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

• ClinicalTrials.gov Identifier: NCT02202395
• Recruitment Status: Completed
• First Posted: July 29, 2014
• Last Update Posted: June 5, 2017
• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
• Information provided by (Responsible Party): Shanghai Pharmaceuticals Holding Co., Ltd

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: LTS 0.25mg; Drug: LTS 0.5mg; Drug: LTS 1.0mg; Drug: Placebo	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: June 2014
• Actual Primary Completion Date: April 30, 2015
• Actual Study Completion Date: December 28, 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 0.25mg; LTS 0.25mg,qd MTX qw	Drug: LTS 0.25mg; use LTS 0.25mg/d; Other Name: Hydroxytriptolide
Active Comparator: 0.5mg; LTS 0.5mg, qd MTX qw	Drug: LTS 0.5mg; use LTS 0.5mg/d; Other Name: Hydroxytriptolide
Active Comparator: 1.0mg; LTS 1.0mg,qd MTX qw	Drug: LTS 1.0mg; use LTS 1.0mg/d; Other Name: Hydroxytriptolide
Placebo Comparator: Placebo; Placebo qd MTX qw	Drug: Placebo; use placebo once daily

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in ACR 20 at 12 weeks and at 24 weeks [ Time Frame: 12weeks, 24weeks ]

Secondary Outcome Measures :

1. Change from baseline in DAS 28 at 12 weeks and at 24 weeks [ Time Frame: 12weeks, 24weeks ]
2. The proportion of patients reached ACR50 at 12 weeks and 24 weeks [ Time Frame: 12weeks, 24weeks ]
3. The proportion of patients reached ACR70 at 12weeks and 24weeks [ Time Frame: 12weeks,24weeks ]
4. Change from baseline in swollen joint count at 12 weeks and 24 weeks [ Time Frame: 12weeks,24weeks ]
5. Change from baseline in tender joint count at 12weeks and 24weeks [ Time Frame: 12weeks,24weeks ]
6. Change from baseline in the duration of morning stiffness at 12 weeks and 24 weeks [ Time Frame: 12 weeks and 24 weeks ]
7. Change from baseline in rest pain at 12 weeks and 24 weeks [ Time Frame: 12weeks,24weeks ]
8. Change from baseline in PtGA patient global assessment at 12 weeks and 24 weeks [ Time Frame: 12 weeks and 24 weeks ]
9. Change from baseline in PGA physician global assessment at 12 weeks and 24 weeks [ Time Frame: 12 weeks and 24 weeks ]
10. Change from baseline in HAQ health assessment questionnaire at 12 weeks and 24 weeks [ Time Frame: 12 weeks, 24 weeks ]
11. Change from baseline in CRP,ESR,RF,CCP at 12 weeks and 24 weeks [ Time Frame: 12 weeks, 24 weeks ]
12. Change from baseline in IgA, IgG, IgM at 12 weeks and 24 weeks [ Time Frame: 12 weeks, 24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

China, Anhui

The first affiliated hospital of bengbu medical college

Bengbu, Anhui, China, 233004

China, Shanghai

Changzheng Hospital

Shanghai, Shanghai, China, 200003

Zhongshan Hospital Fudan University

Shanghai, Shanghai, China, 200032

Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee

Shanghai, Shanghai, China, 200127

Changhai Hospital

Shanghai, Shanghai, China, 200433

Sponsors and Collaborators

Shanghai Pharmaceuticals Holding Co., Ltd

Investigators

• Principal Investigator: Chunde Bao, MD; Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee

More Information

• Responsible Party: Shanghai Pharmaceuticals Holding Co., Ltd
• ClinicalTrials.gov Identifier: NCT02202395
• Other Study ID Numbers: LTS-201-P1.0
• First Posted: July 29, 2014
• Last Update Posted: June 5, 2017
• Last Verified: June 2017

Keywords provided by Shanghai Pharmaceuticals Holding Co., Ltd:

Hydroxytriptolide; Rheumatoid Arthritis; Methotrexate; T8; LTS

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases