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The Clinical Efficacy of Immunomodulators in RA Patients

Primary Purpose

Arthritis, Rheumatoid

Status

Recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Iguratimod

Methotrexate

Adalimumab Injection

Leflunomide

Hydroxychloroquine

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring csDMARDs, TNFi

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. ACR 1987 rheumatoid arthritis classification criteria morning stiffness lasting at least 1 hour (≥6w) there are 3 or more joint areas swollen (≥6w) swelling of the wrist, metacarpophalangeal, and proximal phalangeal joint areas (≥6w) symmetrical arthrogryposis (≥6w) hand x-ray changes (at least osteoporosis and joint space narrowing) positive rheumatoid factor (titer > 1:32) RA can be diagnosed by meeting 4 of the above 7 items ACR/EULAR 2010 rheumatoid arthritis Classification Criteria 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) 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) Acute chronotropic reactants Both CRP and ESR normal (0 points) Abnormal CRP or ESR (1 point) 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: Patients with combined active hepatitis Patients with active tuberculosis Patients withinfection and malignancy

Sites / Locations

Qilu HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Methotrexate(MTX)+Iguratimod(IGU)

Adalimumab+Methotrexate(MTX)

Iguratimod(IGU)+Leflunomide(LEF)+Hydroxychloroquine(HCQ)

Arm Description

Drug: Iguratimod（IGU），25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Methotrexate(MTX)，10mg, po, quaque week (qw) prescribed at the beginning and adjusted due to patient response. For RA patients with naive or csDMARDs-IR

Drug: Adalimumab，40mg, iH,q2w, once two weeks (q2w) prescribed at the beginning and adjusted due to patient response. Drug: Methotrexate(MTX)，7-10mg, po, quaque week (qw) prescribed at the beginning and adjusted due to patient response. For RA patients with csDMARDs-IR

Drug: Iguratimod（IGU），25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Leflunomide(LEF)，20mg, po, quaque day (qd) prescribed at the beginning and adjusted due to patient response. Drug: Hydroxychloroquine(HCQ)，200mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. For RA patients with csDMARDs-IR

Outcomes

Primary Outcome Measures

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 = 0.56√(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.

Secondary Outcome Measures

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) .

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.

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).

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.

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 <CDAI ≤ 22, moderate disease activity; 2.8 <CDAI ≤10, low disease activity; remission is CDAI score ≤2.8.

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.

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.

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.

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.

Incidence of participant withdrawal

Percentage of participants who withdraw from this study.

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.

Full Information

NCT ID

NCT05626348

First Posted

November 15, 2022

Last Updated

November 28, 2022

Sponsor

Qilu Hospital of Shandong University

1. Study Identification

Unique Protocol Identification Number

NCT05626348

Brief Title

The Clinical Efficacy of Immunomodulators in RA Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 22, 2021 (Actual)

Primary Completion Date

June 30, 2025 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Qilu Hospital of Shandong University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Arthritis, Rheumatoid

Keywords

csDMARDs, TNFi

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Methotrexate(MTX)+Iguratimod(IGU)

Arm Type

Experimental

Arm Description

Arm Title

Adalimumab+Methotrexate(MTX)

Arm Type

Experimental

Arm Description

Arm Title

Iguratimod(IGU)+Leflunomide(LEF)+Hydroxychloroquine(HCQ)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Iguratimod

Other Intervention Name(s)

IGU, T-614

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

MTX

Intervention Description

Methotrexate，10mg, po, quaque week (qw) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.

Intervention Type

Drug

Intervention Name(s)

Adalimumab Injection

Other Intervention Name(s)

adalimu

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Leflunomide

Other Intervention Name(s)

LEF

Intervention Description

Leflunomide，20mg, po, quaque day (qd) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.

Intervention Type

Drug

Intervention Name(s)

Hydroxychloroquine

Other Intervention Name(s)

HCQ

Intervention Description

Hydroxychloroquine，200mg, po, twice per day (bid) prescribed at the beginning and adjusted due to patient response. Then may titer down until the endpoint.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

week 24

Secondary Outcome Measure Information:

Title

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

Description

The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) .

Time Frame

week 12

Title

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

Description

Time Frame

baseline,week 12,week 24

Title

Percentage of participants achieving ACR/EULAR remission

Description

Time Frame

week 12,week 24

Title

Change from baseline Simplified Disease Activity Index (SDAI)

Description

Time Frame

up to week 24

Title

Change from baseline Clinical Disease Activity Index (CDAI)

Description

Time Frame

up to week 24

Title

Change From Baseline in C-reactive Protein (CRP)

Description

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 24

Title

Change From Baseline in Erythrocyte Sedimentation Rate (ESR)

Description

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 24

Title

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

Description

Time Frame

up to week 24

Title

Percentage of American College of Rheumatology [ACR] 20、 [ACR]50、 [ACR]70 Criteria Responders every time

Description

Percentage of American College of Rheumatology [ACR] 20、 [ACR]50、 [ACR]70 Criteria Responders every time.

Time Frame

up to week 24

Title

Incidence of participant withdrawal

Description

Percentage of participants who withdraw from this study.

Time Frame

up to week 24

Title

Number of participants with"adverse events (AEs)"

Description

Time Frame

up to week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Qiang Shu, Dr.

Phone

0086-0531-82169654

shuqiang@sdu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Bingbing Ren

Phone

0086-18765361979

sdrenbingbing@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xiaoyun Yang

Organizational Affiliation

Qilu Hospital of Shandong University

Official's Role

Study Director

Facility Information:

Facility Name

Qilu Hospital

City

Jinan

State/Province

Shandong

ZIP/Postal Code

250012

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Xiaoyun Yang, Dr.

Phone

0086-0531-82169166

qlyykyc@163.com

12. IPD Sharing Statement

Learn more about this trial

The Clinical Efficacy of Immunomodulators in RA Patients

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