A Clinical Study of TQH3821 Tablets in the Treatment of Treated Rheumatoid Arthritis

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of TQH3821 in treated patients with moderate-to-severe active rheumatoid arthritis.

Official Title
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Randomized, Double-blind, Placebo-controlled, Multicenter Phase II Trial to Evaluate the Efficacy and Safety of TQH3821 Tablets in Patients With Treated Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: TQH3821 tablets 200 mg
* Drug: TQH3821 tablets matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily participate in this study and sign informed consent; Male and female, ≥18 years old and ≤70 years old (subject to the date of signing the informed consent); The diagnosis meets the rheumatoid arthritis (RA) classification criteria jointly established by the American College of Rheumatology (ACR) and the European Alliance against Rheumatism (EULAR) in 2010, for at least 3 months ; Moderate to severe active RA was defined by the following criteria: joint swelling ≥6 (based on 66 joints), joint tenderness ≥6 (based on 68 joints), Disease activity score 28-C-reactive protein (DAS28-CRP) ≥3.2, and CRP>10mg/L or erythrocyte sedimentation rate (ESR) >28mm/h; At least 12 weeks of treatment with methotrexate (dose 7.5 to 25 mg/ week) and stable dose (7.5 to 25 mg/ week) ≥4 weeks prior to initial administration of the study drug (oral stable dose methotrexate will be continued as background therapy during the trial); The subjects can attend the study visit on time and complete the visit; Exclusion Criteria: 8 weeks before baseline examination, subjects underwent joint surgery or received intraarticular glucocorticoid therapy at the joint sites evaluated in this study; Patients with rheumatoid arthritis with joint functional activity grade Ⅳ or confined to a wheelchair or bed; Current or previous inflammatory joint diseases other than RA and other autoimmune venereal diseases; Patients with lung diseases deemed unsuitable for the study by the investigator; Cardiovascular and cerebrovascular abnormalities; Abnormal thyroid function; Subjects with a history or suspected demyelinating disease of the central nervous system; Have any type of active malignant tumor or have a history of malignant tumor; Presence of active Mycobacterium tuberculosis (TB) infection or latent TB infection without appropriate treatment; Have any acute or chronic active infectious disease; There are serious poorly controlled diseases; People with active hepatitis, or hepatitis B surface antigen (HBsAg) positive, hepatitis B core antibody (HBcAb) positive + hepatitis B virus (HBV) DNA positive, or hepatitis C virus (HCV) antibody-positive; History of human immunodeficiency virus (HIV) infection, or positive HIV serological results at screening, and positive antibodies to treponema pallidum during screening; Subjects who had suffered a severe trauma, fracture, or surgical procedure within 8 weeks prior to screening, or who were expected to require major surgical procedures during the study period; Female subjects who are pregnant or lactating; Those who received live attenuated vaccine within 28 days before the start of treatment, inactivated vaccine within 7 days, or planned vaccination during the study period; The subject has any medical condition that may affect oral drug absorption, gastrectomy or gastrointestinal disease of clinical significance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQH3821 tablets 200 mg<br>Oral administration of TQH3821 tablets 200 mg, twice a day for 24 weeks. | Drug: TQH3821 tablets 200 mg<br>* TQH3821 is a Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) inhibitor.<br>|
| Placebo Comparator: TQH3821 tablets matching placebo<br>The placebo group was taken orally until the end of week 12. At the end of week 12, the placebo group was switched to the oral administration of TQH3821 tablets 200 mg until the end of week 24. | Drug: TQH3821 tablets 200 mg<br>* TQH3821 is a Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) inhibitor.<br>Drug: TQH3821 tablets matching placebo<br>* TQH3821 tablets matching placebo without active substance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology 20 (ACR20) improvement | Proportion of patients with ACR20 at week 12. | Evaluated at week 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology 20 (ACR20) improvement | Proportion of patients with ACR20. | Evaluated at week 4, 8, 18, and 24. | 
| American College of Rheumatology 50 (ACR50) improvement | Proportion of patients with ACR20. | Evaluated at week 4, 8, 12, 18, and 24. | 
| C-reactive protein (CRP) | Changes in C-reactive protein (CRP) relative to baseline. | Evaluated at week 4, 8, 12, 18, and 24. | 
| Erythrocyte sedimentation rate (ESR) | Changes in erythrocyte sedimentation rate (ESR) relative to baseline. | Evaluated at week 4, 8, 12, 18, and 24. | 
| 66 joint swelling counts (SJC) | Change in the number of 66 joint swelling relative to baseline. | Evaluated at week 4, 8, 12, 18, and 24. | 
| 68 joint tenderness counts (TJC) | Change in the number of 68 joint tenderness numbers (TJC) relative to baseline. | Evaluated at week 4, 8, 12, 18, and 24. | 
| Disease activity score 28-C-reactive protein (DAS28-CRP) | Changes in disease activity score DAS28 -CRP relative to baseline. | Evaluated at week 4, 8, 12, 18, and 24. | 
| Patient's visual analogue score (PVAS) | PVAS is a questionnaire to evaluate joint pain in subjects with scores from 0 to 10, where 0 means no pain and 10 means the worst pain. | Evaluated at week 4, 8, 12, 18, and 24. | 
| Patient's global assessment (PtGA) | PtGA is a questionnaire to evaluate arthritis score by patient's overall assessment, with scores from 0 to 10, where 0 means very good and 10 means very poor. | Evaluated at week 4, 8, 12, 18, and 24. | 
| Physician's global assessment (PhGA) | PhGA is a questionnaire to evaluate arthritis score by physician's overall assessment, with scores from 0 to 10, where 0 means very good and 10 means very poor. | Evaluated at week 4, 8, 12, 18, and 24. | 
| Health Assessment questionnaire-Disability Index (HAQ-DI) | HAQ-DI is a questionnaire to evaluate quality of life of subjects with scores from 0 to 3, 0 means easy and 3 means very difficult. | Evaluated at week 4, 8, 12, 18, and 24. | 
| Incidence of adverse events | Incidence of adverse events after administration. | Baseline up to 28 weeks. | 
| Severity of adverse events | Severity of adverse events after administration. | Baseline up to 28 weeks. |