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

Qilu Hospital of Shandong University400 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

400

Conditions

Arthritis, Rheumatoid

Interventions

IguratimodDRUG

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.

MTXDRUG

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

HCQDRUG

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

Eligibility

Sex: ALLMin age: 16 YearsMax age: 90 Years

Medical Language ↔ Plain English

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.

Locations (1)

Qilu Hospital

Jinan, Shandong, China

Outcomes

Primary Outcomes

The percentage of patients who achieve clinical remission at week 24 using European League Against Rheumatism (EULAR) response criteria DAS28

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.

Time frame: week 24

Secondary Outcomes

The percentage of patients who achieve clinical remission using DAS28-ESR at 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.

Time frame: week 12

The percentage of patients who achieve clinical remission using DAS28-ESR at 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.

Time frame: week 48

The percentage of patients who achieve clinical remission using DAS28-ESR at 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.

Data from ClinicalTrials.gov

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

Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at 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.

Time frame: week 12

Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at 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.

Time frame: week 24

Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 48

Time frame: week 48

Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 96

Time frame: week 96

Percentage of participants achieving ACR/EULAR remission at 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).

Time frame: week 12

Percentage of participants achieving ACR/EULAR remission at week 24

Time frame: week 24

Percentage of participants achieving ACR/EULAR remission at week 48

Time frame: week 48

Percentage of participants achieving ACR/EULAR remission at week 96

Time frame: week 96

Percentage of American College of Rheumatology [ACR] 20 Criteria Responders every 3 months

Percentage of American College of Rheumatology \[ACR\] 20 Criteria Responders every 3 months

Time frame: Up to week 96

Change from baseline Simplified Disease Activity Index (SDAI)

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.

Time frame: Up to week 96

Change from baseline Clinical Disease Activity Index (CDAI)

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.

Time frame: Up to week 96

Change From Baseline in C-reactive Protein (CRP)

Change from Baseline in C-reactive Protein (CRP), a component index of ACR20 and SDAI, CRP will be measured with blood samples.

Time frame: Up to week 96

Change From Baseline in Erythrocyte Sedimentation Rate (ESR)

Change from Baseline in ESR, that is a component index of ACR20, DAS28-ESR and SDAI, ESR will be measured with blood samples.

Time frame: Up to week 96

Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI)

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.

Time frame: Up to week 96

Incidence of participant withdrawal

Percentage of participants who withdraw from this study.

Time frame: Up to week 96

Number of participants with"adverse events (AEs)"

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.

Time frame: Up to week 96