The Clinical Efficacy of Immunomodulators in RA Patients

Arthritis, Rheumatoid Clinical Trial

Official title:

The Clinical Study to Observe the Efficacy and Safety of Immunomodulators in Rheumatoid Arthritis Patients for 6 Months Treatment in China

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05626348
• Other study ID #: Response of DMARDs in RA QiluH
• Status: Recruiting
• Phase: Phase 4
• Start date: December 22, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: November 2022
• Source: Qilu Hospital of Shandong University
• Contact: Qiang Shu, Dr.
• Phone: 0086-0531-82169654
• Email: shuqiang[@]sdu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study includes naive patients and csDMARDs-IR RA patients, treated with different regimens such as Iguratimod combination of different csDMARDs, or csDMARD with TNF inhibitors for 24 weeks. The disease activity and drug response will be observed. The immune disorder and synovial function will be evaluated at the same time.

Description:

In this study cohorts, naïve or csDMARDs-IR patients are treated with different csDMARDs combination or TNF inhibitors for 24 weeks to get remission in clinical. The biomarkers in their plasma and synovial fluid and tissue specimens from RA patients are screened to predict the efficacy of specific treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

-

1.Patients with RA who meet ACR 1987 rheumatoid arthritis classification criteria or ACR/EULAR 2010 rheumatoid arthritis Classification Criteria and have knee dysfunction.

1. ACR 1987 rheumatoid arthritis classification criteria

1. morning stiffness lasting at least 1 hour (=6w)

2. there are 3 or more joint areas swollen (=6w)

3. swelling of the wrist, metacarpophalangeal, and proximal phalangeal joint areas (=6w)

4. symmetrical arthrogryposis (=6w)

5. hand x-ray changes (at least osteoporosis and joint space narrowing)

6. positive rheumatoid factor (titer > 1:32) RA can be diagnosed by meeting 4 of the above 7 items

2. ACR/EULAR 2010 rheumatoid arthritis Classification Criteria

1. Involved joints

• 1 large joint (0 points)

• 2-10 large joints (1 point)

• 1-3 small joints (with or without large joints) (2 points)

• 4-10 small joints (with or without large joints) (3 points)

• more than 10 small joints (at least one small joint) (5 points)

2. Serological indicators

• RF and ACPA negative (0 points)

• RF and ACPA, at least one of which is low titer positive. (2 points)

• RF and ACPA with at least one high titer positive (3 points)

3. Acute chronotropic reactants

• Both CRP and ESR normal (0 points)

• Abnormal CRP or ESR (1 point)

4. Duration of synovitis

• <6 weeks (0 points)

• =6 weeks (1 point)

2.Patients with OA who meet the 1995 Classification Criteria for OA and have knee dysfunction 1995 Classification Criteria for Osteoarthritis of the Knee Clinical criteria

a. Knee pain most of the time in the last 1 month b. Bone rubbing sound c, morning stiffness = 30 minutes d, age = 38 years e, with bony enlargement Knee OA can be diagnosed if a+b+c+d or a+b+e is met

3.Age-sex matched healthy volunteers who checked in our hospital.

4.Age > 18 years old;

5.Voluntarily participate in this study and sign an informed consent form

Exclusion Criteria:

1. Patients with combined active hepatitis

2. Patients with active tuberculosis

3. Patients withinfection and malignancy

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

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.
• Methotrexate
Methotrexate,10mg, po, quaque week (qw) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.
• Adalimumab Injection
Adalimumab Injection,40mg,iH,every two weeks (q2w) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.
• Leflunomide
Leflunomide,20mg, po, quaque day (qd) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.
• Hydroxychloroquine
Hydroxychloroquine,200mg, po, twice per day (bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.

Locations

Country	Name	City	State
China	Qilu Hospital	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Qilu Hospital of Shandong University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of patients who achieve clinical remission 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 = 0.56v(TJC) + 0.28v(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.	week 24
Secondary	The percentage of patients who achieve clinical remission using DAS28-ESR.	The percentage of patients whose DAS28 achieve remission(DAS28-ESR= 2.6)and Low Disease Activity (DAS28-ESR = 3.2) .	week 12
Secondary	Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders	?DAS28 indicates the decline of DAS28-ESR from the baseline to week 30. 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 30 = 3.2. Moderate responders: ?DAS28 > 1.2 and still DAS28 > 3.2 at week 30, or 1.2 =?DAS28 > 0.6 and DAS28 = 5.1 at week 30. Nonresponders:?DAS28 =0.6 or DAS28 >5.1 at week 30. DAS28-defined remission was classified as a score of <2.6.	baseline,week 12,week 24
Secondary	Percentage of participants achieving ACR/EULAR remission	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).	week 12,week 24
Secondary	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	up to week 24
Secondary	Change from baseline Clinical Disease Activity Index (CDAI)	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	up to week 24
Secondary	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.	up to week 24
Secondary	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.	up to week 24
Secondary	Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI)	hange 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.	up to week 24
Secondary	Percentage of American College of Rheumatology [ACR] 20? [ACR]50? [ACR]70 Criteria Responders every time	Percentage of American College of Rheumatology [ACR] 20? [ACR]50? [ACR]70 Criteria Responders every time.	up to week 24
Secondary	Incidence of participant withdrawal	Percentage of participants who withdraw from this study.	up to week 24
Secondary	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.	up to week 24