Clinical trial NCT05803135: Iguratimod Combined With Tofacitinib in the Treatment of Rheumatoid Arthritis
Official title: Efficacy and Safety of Iguratimod Combined With Tofacitinib in the Treatment of csDMARD-IR Patients With Active Moderate-to-severe Rheumatoid Arthritis： a Prospective, Randomized, Controlled, Multicenter Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Rheumatoid Arthritis
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Jiangsu Simcere Pharmaceutical Co., Ltd.
First posted: 2023-04-07
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, randomized, controlled, multicenter study
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of Iguratimod combined with Tofacitinib in the treatment of csDMARD-IR patients with active moderate-to-severe rheumatoid arthritis

Detailed description: After being informed about the study and potential risks, all patients giving written informed consent will undergo a 1-week screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a double-blind manner (participant and investigator) in a 1:1 ratio to Iguratimod (25mg, twice daily) combined with Tofacitinib (5mg, twice daily) or placebo (25mg, twice daily) combined with Tofacitinib (5mg, twice daily).

Eligibility criteria: Inclusion Criteria:

Patients who meet the following inclusion criteria will be eligible to participate in the study:

1. Male or female aged 18-65 years old;
2. Weight not less than 40kg;
3. Since the diagnosis of RA, the course of disease was ≥6 months;
4. Patients who meet RA standards in 1987 and 2010 ;
5. RA patients with moderate to high disease activity (DAS28 \> 3.2) at the time of screening;
6. Active RA (≥6 joints swelling \[66 joints count\]; ≥Tenderness of 6 joints \[68 joint counts\]; ESR\>28 mm/h or C-reactive protein (CRP) \>1.0 mg/dL);
7. Poor response or intolerance to at least one DMARD, including csDMARDs, bDMARDs, but not tsDMARDs;
8. Previous use of any JAK inhibitor was discontinued for six months before enrollment;
9. For patients who have used DMARDs, the washout criteria must be met;
10. Written informed consent;

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from the study:

* Pregnant or lactating women;
* Platelet count \< 10\^9/L, or white blood cell \< 3\*10\^9/L, or absolute neutrophil count \< 1.2\*10\^9/L, or Hemoglobin \< 9 g/dL or hematocrit \<30%;
* According to Cockcroft-Gault, the glomerular filtration rate was ≤40 ml/min.
* ALT\>1.5×ULN, AST\>1.5×ULN, Cr\>135umol/L;
* Subjects with serious cardiovascular, renal, hematologic or endocrine diseases;
* A history of autoimmune rheumatic diseases other than Sjogren's syndrome;
* Subjects with uncontrolled infection;
* Subjects receiving live vaccines within 6 weeks prior to study entry;
* history of alcohol or drug abuse and abstinence for less than 6 months prior to the first use of the study drug;
* Subjects participating in other clinical study within 3 months prior to study entry;
* Have a history of malignant tumor;
* History of recurrent herpes zoster, diffuse herpes zoster;
* People who are allergic to any of the study drugs;
* Other conditions in which the investigator deemed the patient inappropriate for trial entry;

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: Percentage of American College of Rheumatology [ACR] 20 Criteria Responders at the end of 24 weeks was compared between the two groups.
timeFrame: week 24
measure: Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at the end of 24 weeks was compared between the two groups.
timeFrame: week 24
measure: Percentage of American College of Rheumatology [ACR] 70 Criteria Responders at the end of 24 weeks was compared between the two groups.
timeFrame: week 24
measure: The change of DAS28 score between the two groups at the end of 24 weeks was compared with the baseline value (week 0)
timeFrame: up to week 24
measure: The change of Clinical Disease Activity Index (CDAI) score between the two groups at the end of 24 weeks was compared with the baseline value (week 0)
timeFrame: up to week 24
measure: The change of Simplified Disease Activity Index (SDAI) score between the two groups at the end of 24 weeks was compared with the baseline value (week 0)
timeFrame: up to week 24
measure: The percentage of patients who achieve clinical remission at week 12 using European League Against Rheumatism (EULAR) response criteria DAS28
timeFrame: week 12
measure: The proportion of patients with SDAI≤3.3 at the end of 24 weeks was compared between the two groups.
timeFrame: week 24
measure: The proportion of patients with CDAI≤2.8 at the end of 24 weeks was compared between the two groups.
timeFrame: week 24
measure: The changes of ACPA, RF, serum immunoglobulin (IgG, IgA, IgM) levels between the two groups at the end of 24 weeks were compared with the baseline values (week 0).
timeFrame: up to week 24
measure: The drug retention rate was compared between the two groups at the end of 12 and 24 weeks.
timeFrame: week 12 and 24
measure: The proportion of patients with minimal clinically important difference (MCID) of 0.22 on the Health Assessment Questionnaire Disability Index (HAQ-DI) was compared between the two groups at the end of 24 weeks.
timeFrame: week 24
Other outcomes:
measure: The change of EULAR Sjögren's Syndrome Discasc Activity Index (ESSDAI) score between the two groups associated with Sjögren's Syndrome (SS) at the end of 24 weeks was compared with the baseline value (week 0)
timeFrame: up to week 24
measure: The change of EULAR Sjögren's Syndrome Patient-Reported Index (ESSPRI) score between the two groups associated with Sjögren's Syndrome (SS) at the end of 24 weeks was compared with the baseline value (week 0)
timeFrame: up to week 24
measure: Number of participants with"adverse events (AEs)"
timeFrame: up to week 24
Locations:
Study officials:
References: