<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02202395</url>
  </required_header>
  <id_info>
    <org_study_id>LTS-201-P1.0</org_study_id>
    <nct_id>NCT02202395</nct_id>
  </id_info>
  <brief_title>Hydroxytriptolide in Active Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate</brief_title>
  <acronym>T8</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Pharmaceuticals Holding Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Pharmaceuticals Holding Co., Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the efficacy and safety of Hydroxytriptolide(LTS)&#xD;
      in active rheumatoid arthritis patients with an inadequate response to methotrexate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Investigate the efficacy of Hydroxytriptolide in active RA patients&#xD;
&#xD;
        2. Investigate the safety of Hydroxytriptolide in active RA patients. Especially in female&#xD;
           reproductive system.&#xD;
&#xD;
        3. Population PK study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">December 28, 2016</completion_date>
  <primary_completion_date type="Actual">April 30, 2015</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in ACR 20 at 12 weeks and at 24 weeks</measure>
    <time_frame>12weeks, 24weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in DAS 28 at 12 weeks and at 24 weeks</measure>
    <time_frame>12weeks, 24weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients reached ACR50 at 12 weeks and 24 weeks</measure>
    <time_frame>12weeks, 24weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients reached ACR70 at 12weeks and 24weeks</measure>
    <time_frame>12weeks,24weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in swollen joint count at 12 weeks and 24 weeks</measure>
    <time_frame>12weeks,24weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in tender joint count at 12weeks and 24weeks</measure>
    <time_frame>12weeks,24weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in the duration of morning stiffness at 12 weeks and 24 weeks</measure>
    <time_frame>12 weeks and 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in rest pain at 12 weeks and 24 weeks</measure>
    <time_frame>12weeks,24weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in PtGA patient global assessment at 12 weeks and 24 weeks</measure>
    <time_frame>12 weeks and 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in PGA physician global assessment at 12 weeks and 24 weeks</measure>
    <time_frame>12 weeks and 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in HAQ health assessment questionnaire at 12 weeks and 24 weeks</measure>
    <time_frame>12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in CRP,ESR,RF,CCP at 12 weeks and 24 weeks</measure>
    <time_frame>12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in IgA, IgG, IgM at 12 weeks and 24 weeks</measure>
    <time_frame>12 weeks, 24 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>0.25mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>LTS 0.25mg,qd MTX qw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.5mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>LTS 0.5mg, qd MTX qw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1.0mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>LTS 1.0mg,qd MTX qw</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo qd MTX qw</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LTS 0.25mg</intervention_name>
    <description>use LTS 0.25mg/d</description>
    <arm_group_label>0.25mg</arm_group_label>
    <other_name>Hydroxytriptolide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LTS 0.5mg</intervention_name>
    <description>use LTS 0.5mg/d</description>
    <arm_group_label>0.5mg</arm_group_label>
    <other_name>Hydroxytriptolide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LTS 1.0mg</intervention_name>
    <description>use LTS 1.0mg/d</description>
    <arm_group_label>1.0mg</arm_group_label>
    <other_name>Hydroxytriptolide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>use placebo once daily</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  35-65 years old, female, postmenopausal, parous, nulliparous with no fertility&#xD;
             requirements&#xD;
&#xD;
          -  1987 ACR Diagnostic criteria or 2009 ACR/EULAR Diagnostic criteria. X ray of Evaluable&#xD;
             Joint in phase I/II/III, Joint Function in Phase I/II/III&#xD;
&#xD;
          -  Active RA&#xD;
&#xD;
          -  Continuously taking MTX for at least three months, ≥7.5mg/week. Before first study&#xD;
             dose, keep in stable MTX dose for at least 4 weeks&#xD;
&#xD;
          -  Keep in stable NSAIDs dose or low-dose glucocorticoids for at least 4 weeks before&#xD;
             first study dose&#xD;
&#xD;
          -  Using non-prohibited combination therapy, keep in stable dose for at least 7 days&#xD;
             before first study dose&#xD;
&#xD;
          -  Using DMARD should have appropriate withdrawal period:&#xD;
&#xD;
               -  Withdrawal for 4 weeks: Sulfasalazine, Azathioprine, Chloroquine,&#xD;
                  *Hydroxychloroquine, Auranofin, Penicillamine, Traditional Chinese medicine&#xD;
                  preparation(TGP, Sinomenine)&#xD;
&#xD;
               -  Withdrawal for 8 weeks: Leflunomide&#xD;
&#xD;
               -  Withdrawal for 8 weeks: Intramuscular, intravenous, intra-articular injection&#xD;
                  glucocorticoids&#xD;
&#xD;
          -  Women with fertility, negative in pregnancy test, and agreed to take contraceptive&#xD;
             measures physical&#xD;
&#xD;
          -  Voluntary informed consent&#xD;
&#xD;
          -  Willing to follow the required regimen and schedule, follow-up examination&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently suffering or have suffered from other inflammatory joint diseases, such as&#xD;
             mixed connective tissue disease, scleroderma, systemic lupus erythematosus, ankylosing&#xD;
             spondylitis, psoriatic arthritis, Reiter's syndrome, bone arthritis, rheumatoid&#xD;
             arthritis, gouty arthritis, diagnosis of arthritis before 16yrs&#xD;
&#xD;
          2. With severe non-articular manifestations such as high fever, interstitial pneumonia,&#xD;
             pleurisy, pericarditis, severe vasculitis, neuropathy, etc.&#xD;
&#xD;
          3. The evaluable joint underwent the surgical treatment within 2 months&#xD;
&#xD;
          4. Currently or recent have serious, or progression, or disease history not controled,&#xD;
             including: liver, kidney, blood, gastrointestinal, endocrine, metabolic, respiratory,&#xD;
             cardiovascular, nervous system diseases&#xD;
&#xD;
          5. Currently or have malignancy, lymphoproliferative disease history&#xD;
&#xD;
          6. Continuously use Tripterygium preparations for more than three months and have no&#xD;
             effect&#xD;
&#xD;
          7. History of using TNF-a inhibitors of biological agents.(Adalimumab, infliximab,&#xD;
             etanercept)&#xD;
&#xD;
          8. Severe or persistent infection within 3 months&#xD;
&#xD;
          9. X-ray shows active pulmonary infection&#xD;
&#xD;
         10. HBV, HCV, HIV, AIDS&#xD;
&#xD;
         11. WBC&lt;4.0×10^9/L, PLT&lt;100×10^9/L, Hb&lt;85g/L&#xD;
&#xD;
         12. AST&gt;2×ULN, ALT&gt;2×ULN&#xD;
&#xD;
         13. Cr&gt;135umol/L&#xD;
&#xD;
         14. Used oral contraceptive druds within 3 months&#xD;
&#xD;
         15. Pregnancy test was positive or lactating patients or patients with birth preparation&#xD;
&#xD;
         16. Have to use the prohibited drugs&#xD;
&#xD;
         17. With clinical symptoms of a serious history of drug abuse or alcohol abuse&#xD;
&#xD;
         18. History of any durg clinical trials within 3 months&#xD;
&#xD;
         19. Allergy to tripterygium&#xD;
&#xD;
         20. Other reasons depends by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chunde Bao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The first affiliated hospital of bengbu medical college</name>
      <address>
        <city>Bengbu</city>
        <state>Anhui</state>
        <zip>233004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changzheng Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zhongshan Hospital Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Changhai Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>June 2, 2017</last_update_submitted>
  <last_update_submitted_qc>June 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hydroxytriptolide</keyword>
  <keyword>Rheumatoid Arthritis</keyword>
  <keyword>Methotrexate</keyword>
  <keyword>T8</keyword>
  <keyword>LTS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02202395
org study id: LTS-201-P1.0
nct id: NCT02202395
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from baseline in ACR 20 at 12 weeks and at 24 weeks
time frame: 12weeks, 24weeks
measure: Change from baseline in DAS 28 at 12 weeks and at 24 weeks
time frame: 12weeks, 24weeks
measure: The proportion of patients reached ACR50 at 12 weeks and 24 weeks
time frame: 12weeks, 24weeks
measure: The proportion of patients reached ACR70 at 12weeks and 24weeks
time frame: 12weeks,24weeks
measure: Change from baseline in swollen joint count at 12 weeks and 24 weeks
time frame: 12weeks,24weeks
measure: Change from baseline in tender joint count at 12weeks and 24weeks
time frame: 12weeks,24weeks
measure: Change from baseline in the duration of morning stiffness at 12 weeks and 24 weeks
time frame: 12 weeks and 24 weeks
measure: Change from baseline in rest pain at 12 weeks and 24 weeks
time frame: 12weeks,24weeks
measure: Change from baseline in PtGA patient global assessment at 12 weeks and 24 weeks
time frame: 12 weeks and 24 weeks
measure: Change from baseline in PGA physician global assessment at 12 weeks and 24 weeks
time frame: 12 weeks and 24 weeks
measure: Change from baseline in HAQ health assessment questionnaire at 12 weeks and 24 weeks
time frame: 12 weeks, 24 weeks
measure: Change from baseline in CRP,ESR,RF,CCP at 12 weeks and 24 weeks
time frame: 12 weeks, 24 weeks
measure: Change from baseline in IgA, IgG, IgM at 12 weeks and 24 weeks
time frame: 12 weeks, 24 weeks
arm group label: 0.25mg
arm group type: Active Comparator
description: LTS 0.25mg,qd MTX qw
arm group label: 0.5mg
arm group type: Active Comparator
description: LTS 0.5mg, qd MTX qw
arm group label: 1.0mg
arm group type: Active Comparator
description: LTS 1.0mg,qd MTX qw
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo qd MTX qw
intervention type: Drug
intervention name: LTS 0.25mg
description: use LTS 0.25mg/d
arm group label: 0.25mg
other name: Hydroxytriptolide
intervention type: Drug
intervention name: LTS 0.5mg
description: use LTS 0.5mg/d
arm group label: 0.5mg
other name: Hydroxytriptolide
intervention type: Drug
intervention name: LTS 1.0mg
description: use LTS 1.0mg/d
arm group label: 1.0mg
other name: Hydroxytriptolide
intervention type: Drug
intervention name: Placebo
description: use placebo once daily
arm group label: Placebo
criteria: 
gender: Female
minimum age: 35 Years
maximum age: 65 Years
healthy volunteers: No
last name: Chunde Bao, MD
role: Principal Investigator
affiliation: Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid