Clinical trial NCT03855007: The Clinical Efficacy and Safety of Iguratimod in RA and Early RA Patients for 6 Months Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Keywords: Iguratimod
Lead sponsor: Qilu Hospital of Shandong University
Sponsor class: OTHER
First posted: 2019-02-26
Enrollment: 400
Sex: ALL
Minimum age (years): 16
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The percentage of patients who achieve clinical remission at week 24 using European League Against Rheumatism (EULAR) response criteria DAS28
timeFrame: week 24
Secondary outcomes:
measure: The percentage of patients who achieve clinical remission using DAS28-ESR at week 12
timeFrame: week 12
measure: The percentage of patients who achieve clinical remission using DAS28-ESR at week 48
timeFrame: week 48
measure: The percentage of patients who achieve clinical remission using DAS28-ESR at week 96
timeFrame: week 96
measure: Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 12
timeFrame: week 12
measure: Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 24
timeFrame: week 24
measure: Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 48
timeFrame: week 48
measure: Percentage of Disease Activity Score 28 (DAS28)-ESR Criteria Responders at week 96
timeFrame: week 96
measure: Percentage of participants achieving ACR/EULAR remission at week 12
timeFrame: week 12
measure: Percentage of participants achieving ACR/EULAR remission at week 24
timeFrame: week 24
measure: Percentage of participants achieving ACR/EULAR remission at week 48
timeFrame: week 48
measure: Percentage of participants achieving ACR/EULAR remission at week 96
timeFrame: week 96
measure: Percentage of American College of Rheumatology [ACR] 20 Criteria Responders every 3 months
timeFrame: Up to week 96
measure: Change from baseline Simplified Disease Activity Index (SDAI)
timeFrame: Up to week 96
measure: Change from baseline Clinical Disease Activity Index (CDAI)
timeFrame: Up to week 96
measure: Change From Baseline in C-reactive Protein (CRP)
timeFrame: Up to week 96
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Up to week 96
measure: Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: Up to week 96
measure: Incidence of participant withdrawal
timeFrame: Up to week 96
measure: Number of participants with"adverse events (AEs)"
timeFrame: Up to week 96
Other outcomes:
Locations:
city: Jinan
country: China
facility: Qilu Hospital
state: Shandong
Study officials:
affiliation: Qilu Hospital of Shandong University
name: Ming Lv, Dr.
role: STUDY_DIRECTOR
References: