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The Clinical Efficacy and Safety of Iguratimod in RA and Early RA Patients for 6 Months Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03855007
Recruitment Status : Active, not recruiting
First Posted : February 26, 2019
Last Update Posted : September 22, 2022
Sponsor:
Information provided by (Responsible Party):
Qiang Shu, Qilu Hospital of Shandong University

Tracking Information
First Submitted Date  ICMJE February 15, 2019
First Posted Date  ICMJE February 26, 2019
Last Update Posted Date September 22, 2022
Actual Study Start Date  ICMJE January 1, 2016
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 23, 2019)
The percentage of patients who achieve clinical remission at week 24 using European League Against Rheumatism (EULAR) response criteria DAS28 [ Time Frame: week 24 ]
The percentage of patients whose Disease Activity Score in 28 Joints (DAS28) achieve remission(DAS28-ESR≤ 2.6)and Low Disease Activity (DAS28-ESR ≤ 3.2). The DAS28 is a composite score derived from 4 of these measures,that is the count of tender joint count(TJC, 0-28)and swollen joint count(SJC, 0-28), measure erythrocyte sedimentation rate (ESR, mm/h) or C reactive protein (CRP, mg/L) and to make a patient assessment of disease activity i.e. 'global assessment of health' (GH) using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst. DAS28 values were calculated as follows: DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x GH. High disease activity: DAS28-ESR > 5.1; Moderate disease activity: 5.1≥ DAS28 > 3.2 to 5.1; Low disease activity (LDA) and Remission mean Clinical remission.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2022)
  • The percentage of patients who achieve clinical remission using DAS28-ESR at week 12 [ Time Frame: week 12 ]
    The percentage of patients whose DAS28 achieve remission(DAS28-ESR≤ 2.6)and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 12.
  • The percentage of patients who achieve clinical remission using DAS28-ESR at week 48 [ Time Frame: week 48 ]
    The percentage of patients whose DAS28 achieve remission(DAS28-ESR≤ 2.6)and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 12.response states were classified as follows: good responders were patients with an improvement from baseline (△DAS28-ESR) of > 1.2 and a DAS28-ESR at week 12 ≤ 3.2. Moderate responders: △DAS28 > 1.2 and still DAS28 > 3.2 at week 12, or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 12. Nonresponders:△DAS28 ≤0.6 or DAS28 >5.1 at week 12. DAS28-defined remission was classified as a score of <2.6.
  • The percentage of patients who achieve clinical remission using DAS28-ESR at week 96 [ Time Frame: week 96 ]
    The percentage of patients whose DAS28 achieve remission(DAS28-ESR≤ 2.6)and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 12Nonresponders:△DAS28 ≤0.6,or DAS28 >5.1 at week 24. DAS28-defined remission was classified as a score of <2.6.
  • Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 12 [ Time Frame: week 12 ]
    △DAS28 indicates the decline of DAS28-ESR from the baseline to week 12. EULAR response states were classified as follows: good responders were patients with an improvement from baseline (△DAS28-ESR) of > 1.2 and a DAS28-ESR at week 12 ≤ 3.2. Moderate responders: △DAS28 > 1.2 and still DAS28 > 3.2 at week 12, or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 12. Nonresponders:△DAS28 ≤0.6 or DAS28 >5.1 at week 12. DAS28-defined remission was classified as a score of <2.6.
  • Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 24 [ Time Frame: week 24 ]
    EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 24. Moderate responders:△DAS28 > 1.2 and still DAS28 > 3.2 at week 24; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 24. Nonresponders:△DAS28 ≤0.6,or DAS28 >5.1 at week 24. DAS28-defined remission was classified as a score of <2.6.
  • Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 48 [ Time Frame: week 48 ]
    EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 24. Moderate responders:△DAS28 > 1.2 and still DAS28 > 3.2 at week 24; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 24. Nonresponders:△DAS28 ≤0.6,or DAS28 >5.1 at week 24. DAS28-defined remission was classified as a score of <2.6.
  • Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 96 [ Time Frame: week 96 ]
    EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 24. Moderate responders:△DAS28 > 1.2 and still DAS28 > 3.2 at week 24; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 24. Nonresponders:△DAS28 ≤0.6,or DAS28 >5.1 at week 24. DAS28-defined remission was classified as a score of <2.6.
  • Percentage of participants achieving ACR/EULAR remission at week 12 [ Time Frame: week 12 ]
    If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, Patient global assessment(PGA) ≤ 1 cm (on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease).
  • Percentage of participants achieving ACR/EULAR remission at week 24 [ Time Frame: week 24 ]
    If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, Patient global assessment(PGA) ≤ 1 cm (on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease).
  • Percentage of participants achieving ACR/EULAR remission at week 48 [ Time Frame: week 48 ]
    If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, Patient global assessment(PGA) ≤ 1 cm (on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease).
  • Percentage of participants achieving ACR/EULAR remission at week 96 [ Time Frame: week 96 ]
    If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, Patient global assessment(PGA) ≤ 1 cm (on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease).
  • Percentage of American College of Rheumatology [ACR] 20 Criteria Responders every 3 months [ Time Frame: Up to week 96 ]
    Percentage of American College of Rheumatology [ACR] 20 Criteria Responders every 3 months
  • Change from baseline Simplified Disease Activity Index (SDAI) [ Time Frame: Up to week 96 ]
    The SDAI is a composite score derived from these measures,that is the count of tender joint count(TJC, 0-28), swollen joint count(SJC, 0-28), C-reactive protein (CRP, mg/L), Patient global assessment(PGA)and physician global assessment(PHGA), each of the last two was assessed on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease. SDAI score will be calculated with formula SDAI = TJC + SJC + PGA+PHGA+ CRP. SDAI score exceeding 26 is considered high disease activity; 11 <SDAI ≤26,moderate disease activity; 3.3 <SDAI ≤11, low disease activity; remission is SDAI score ≤ 3.3.
  • Change from baseline Clinical Disease Activity Index (CDAI) [ Time Frame: Up to week 96 ]
    CDAI is a composite score derived from these measures,that is the count of tender joint count(TJC, 0-28), swollen joint count(SJC, 0-28), Patient global assessment(PGA)and physician global assessment(PHGA), each of the last two was CDAI score will be calculated with formula CDAI = TJC + SJC + PGA + PHGA. CDAI > 22 is considered high disease activity; 10 <CDAI ≤ 22, moderate disease activity; 2.8 <CDAI ≤10, low disease activity; remission is CDAI score ≤2.8.
  • Change From Baseline in C-reactive Protein (CRP) [ Time Frame: Up to week 96 ]
    Change from Baseline in C-reactive Protein (CRP), a component index of ACR20 and SDAI, CRP will be measured with blood samples.
  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Up to week 96 ]
    Change from Baseline in ESR, that is a component index of ACR20, DAS28-ESR and SDAI, ESR will be measured with blood samples.
  • Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: Up to week 96 ]
    Change from Baseline in HAQ-DI, a participant assessed measure of health assessment, shaveing eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item on a single scale has 4 degrees ranging from 0 (no functional difficulty) to 3 (unable to do), with higher scores indicating severe disease.
  • Incidence of participant withdrawal [ Time Frame: Up to week 96 ]
    Percentage of participants who withdraw from this study.
  • Number of participants with"adverse events (AEs)" [ Time Frame: Up to week 96 ]
    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with"adverse events (AEs)"i.e. physical exam abnormalities,vital sign abnormalities,laboratory value abnormalities,symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2019)
  • The percentage of patients who achieve clinical remission using DAS28-ESR at week 12 [ Time Frame: week 12 ]
    The percentage of patients whose DAS28 achieve remission(DAS28-ESR≤ 2.6)and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 12.
  • Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 12 [ Time Frame: week 12 ]
    △DAS28 indicates the decline of DAS28-ESR from the baseline to week 12. EULAR response states were classified as follows: good responders were patients with an improvement from baseline (△DAS28-ESR) of > 1.2 and a DAS28-ESR at week 12 ≤ 3.2. Moderate responders: △DAS28 > 1.2 and still DAS28 > 3.2 at week 12, or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 12. Nonresponders:△DAS28 ≤0.6 or DAS28 >5.1 at week 12. DAS28-defined remission was classified as a score of <2.6.
  • Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 24 [ Time Frame: week 24 ]
    EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 24. Moderate responders:△DAS28 > 1.2 and still DAS28 > 3.2 at week 24; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 24. Nonresponders:△DAS28 ≤0.6,or DAS28 >5.1 at week 24. DAS28-defined remission was classified as a score of <2.6.
  • Percentage of American College of Rheumatology [ACR] 20 Criteria Responders [ Time Frame: up to week 24 ]
    Percentage of patients with ACR20 response is the percentage of study participants who achieved ACR20, defined as at least a 20% improvement in tender joint count(TJC, 0-28)and swollen joint count(SJC, 0-28), and in three of five of the following measures from baseline: patient pain intensity assessment(PAP), patient global assessment(PGA)and physician global assessment(PHGA), each was assessed on a visual analog scale ranging from 0-10cm, with higher scores indicating severe disease; Health assessment questionnaire disability index (HAQ-DI,0-3), and an acute phase reactant [erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)].
  • Change from baseline Simplified Disease Activity Index (SDAI) [ Time Frame: up to week 24 ]
    The SDAI is a composite score derived from these measures,that is the count of tender joint count(TJC, 0-28), swollen joint count(SJC, 0-28), C-reactive protein (CRP, mg/L), Patient global assessment(PGA)and physician global assessment(PHGA), each of the last two was assessed on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease. SDAI score will be calculated with formula SDAI = TJC + SJC + PGA+PHGA+ CRP. SDAI score exceeding 26 is considered high disease activity; 11 <SDAI ≤26,moderate disease activity; 3.3 <SDAI ≤11, low disease activity; remission is SDAI score ≤ 3.3.
  • Change from baseline Clinical Disease Activity Index (CDAI) [ Time Frame: up to week 24 ]
    CDAI is a composite score derived from these measures,that is the count of tender joint count(TJC, 0-28), swollen joint count(SJC, 0-28), Patient global assessment(PGA)and physician global assessment(PHGA), each of the last two was CDAI score will be calculated with formula CDAI = TJC + SJC + PGA + PHGA. CDAI > 22 is considered high disease activity; 10 <CDAI ≤ 22, moderate disease activity; 2.8 <CDAI ≤10, low disease activity; remission is CDAI score ≤2.8.
  • Percentage of participants achieving ACR/EULAR remission at 24 weeks [ Time Frame: week 24 or withdraw timepoint ]
    If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, Patient global assessment(PGA) ≤ 1 cm (on a visual analog scale ranging from 0-10 cm, with higher scores indicating severe disease).
  • Change From Baseline in C-reactive Protein (CRP) [ Time Frame: up to week 24 ]
    Change from Baseline in C-reactive Protein (CRP), a component index of ACR20 and SDAI, CRP will be measured with blood samples.
  • Change From Baseline in Erythrocyte Sedimentation Rate (ESR) [ Time Frame: up to week 24 ]
    Change from Baseline in ESR, that is a component index of ACR20, DAS28-ESR and SDAI, ESR will be measured with blood samples.
  • Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: up to week 24 ]
    Change from Baseline in HAQ-DI, a participant assessed measure of health assessment, shaveing eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item on a single scale has 4 degrees ranging from 0 (no functional difficulty) to 3 (unable to do), with higher scores indicating severe disease.
  • Incidence of participant withdrawal due to the lack of efficacy [ Time Frame: up to week 24 ]
    Percentage of participants who withdraw from this study due to the lack of efficacy.
  • Safety assessed by Adverse Events (AEs) [ Time Frame: Up to 24 weeks ]
    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Clinical Efficacy and Safety of Iguratimod in RA and Early RA Patients for 6 Months Treatment
Official Title  ICMJE Prospective Clinical Study to Observe the Efficacy and Safety of Iguratimod in Rheumatoid Arthritis and Early Rheumatoid Arthritis Patients for 6 Months Treatment in China
Brief Summary This study is designed to observed prospectively the efficacy and safety of 6 months treatment of iguratimod alone, or with methotrexate (MTX), hydroxychloroquine (HCQ) and prednisone step by step on Chinese rheumatoid arthritis (RA) and early rheumatoid arthritis (ERA) patients who were naïve or shown insufficiency response or intolerance to DMARDs. If volunteered, patients who completed the 6-month study can continue to follow our plans for 24 months.
Detailed Description This study will enroll 200 cases of rheumatoid arthritis (RA) and early rheumatoid arthritis (ERA) patients in China, who are naïve or shown insufficiency response or intolerance to DMARDs. The participants plan to be treated with iguratimod alone, or along with methotrexate (MTX)/ hydroxychloroquine (HCQ) / prednisone (Pred) step by step for 6 months if participants are in medium or high disease activity (DAS28≥3.2). Participants can choose to continue the study up to 24 months.The efficacy and safety of 6 months and 24 months Iguratimod treatment in RA and ERA patients will be evaluated with DAS28-ESR and other disease activity indices.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Drug: Iguratimod(T-614),25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.

Drug: Methotrexate (MTX),7.5mg to 15mg, po, once per week (Qw) prescribed if needed and adjusted due to patient response or unacceptable toxicity develops.

Drug: Hydroxychloroquine (HCQ),200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.

Drug: Prednisone (Pred): 5-15mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Arthritis, Rheumatoid
Intervention  ICMJE
  • Drug: Iguratimod
    Iguratimod tablet,25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.
    Other Name: T-614
  • Drug: MTX
    MTX,7.5mg to 15mg, po, once per week (Qw) prescribed if needed and adjusted due to patient response or unacceptable toxicity develops.
    Other Name: methotrexate
  • Drug: HCQ
    HCQ,200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.
    Other Name: Hydroxychloroquine
  • Drug: Pred
    Pred, 5-15mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response
    Other Name: Prednisone
Study Arms  ICMJE Experimental: Iguratimod
The participants plan to be treated with iguratimod alone, or along with methotrexate (MTX), hydroxychloroquine (HCQ) , prednisone (Pred) step by step
Interventions:
  • Drug: Iguratimod
  • Drug: MTX
  • Drug: HCQ
  • Drug: Pred
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 23, 2019)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2025
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria: -

  1. RA: Patients diagnosed based on 1987 ACR classification criteria for rheumatoid arthritis(RA);
  2. ERA: Subjects diagnosed by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR); or by 2012 Chinese classification criteria of early rheumatoid arthritis (ERA), and not match the 1987 ACR criteria for RA.
  3. Age ≥16 years;
  4. Extra-articular manifestations (such as pulmonary fibrosis, proteinuria, leukopenia and peripheral neuropathy ) of RA patients are stable or no significant progress;
  5. Patients can be naïve to any DMARDs, or relapse due to DMARDs drug suspended;
  6. Patients have a history of using csDMARDs including csDMARDs(methotrexate,leflunomide, hydroxychloroquine, sulfasalazine, tacrolimus) , any biologic DMARDs(TNFi,tocilizumab or Tofacitinib),glucocorticoid (prednisone,methylprednisolone) or Chinese traditional Medicine(including tripterygium Glycosides, sinomenine)for 3 months, but couldn't achieve clinical remission or intolerance;

Exclusion Criteria:

  1. Patients with acute or chronic infections such as active bacterial, viral, fungal, tuberculosis infection or active hepatitis B;
  2. Platelet counts(PLT) <80 x 10^9 / L, or white blood cell (WBC) <3 x 10^9 / L;
  3. Propionate acid aminotransferase (ALT) or aspartate aminotransferase (AST) is two times higher than the upper limit of normal;
  4. Renal insufficiency: serum Cr ≥ 176 umol / L;
  5. Pregnant or nursing women (breastfeeding) ;
  6. Patients has a history of malignancy (cure time in less than 5 years);
  7. Patients with severe or poorly controlled hypertension, diabetes or cardiac dysfunction;
  8. Other comorbidities that cannot be treated with immune suppressants. In addition, once patients experience severe adverse drug reactions、ineffective treatment or rapid progression of rheumatoid arthritis, then quit this research.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 90 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03855007
Other Study ID Numbers  ICMJE Iguratimod-ERA QiluH
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Qiang Shu, Qilu Hospital of Shandong University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Qilu Hospital of Shandong University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ming Lv, Dr. Qilu Hospital of Shandong University
PRS Account Qilu Hospital of Shandong University
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP