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The Efficacy and Safety of Tofacitinib (TF) With Iguratimod (IGU) on RA

Primary Purpose

Arthritis, Rheumatoid

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Iguratimod
Tofacitinib
Pred
Sponsored by
Qilu Hospital of Shandong University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring Tofacitinib, Iguratimod

Eligibility Criteria

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

Inclusion Criteria:

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

  1. Patients who meet RA standards in 1987 and 2010 or ERA standards in 2012;
  2. Age > 18 years old;
  3. the extrapulmonary manifestations of RA were stable;
  4. Patients with NSAIDs tolerance;
  5. DAS28-ESR is highergreater than 2.6.

Exclusion Criteria:

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

  1. Patients with acute and chronic infection;
  2. Platelet count < 80*10^9/L, or white blood cell < 3*10^9/L;
  3. ALT or AST is 2 times higher than the upper limit of normal value;
  4. Renal insufficiency: serum Cr ≥ 176 umol/L;
  5. Pregnant or lactating women (breastfeeding);
  6. Have a history of malignant tumor (the cure time is less than 5 years);
  7. Patients with severe hypertension and cardiac insufficiency;
  8. Other diseases or conditions in which immune suppressants cannot be used;
  9. People who are allergic to TF.

Sites / Locations

  • Qilu HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Tofacitinib (TF)+Iguratimod (IGU)

Tofacitinib (TF)

Arm Description

Drug: Iguratimod（IGU），25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Tofacitinib（TF），5mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Prednisone （Pred）： 0-10mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response.

Drug: Tofacitinib（TF），5mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Prednisone （Pred）： 0-10mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response.

Outcomes

Primary Outcome Measures

The percentage of patients who achieve clinical remission at week 30 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 at week 18
The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 18.
The percentage of patients who achieve clinical remission using DAS28-ESR at week 6
The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 18.
Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 30
△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 Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 18
EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 18. Moderate responders：△DAS28 > 1.2 and still DAS28 > 3.2 at week 18; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 18. Nonresponders：△DAS28 ≤0.6，or DAS28 >5.1 at week 18. DAS28-defined remission was classified as a score of <2.6.
Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 6
EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 6. Moderate responders：△DAS28 > 1.2 and still DAS28 > 3.2 at week 6; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 6. Nonresponders：△DAS28 ≤0.6，or DAS28 >5.1 at week 6. DAS28-defined remission was classified as a score of <2.6.
Percentage of participants achieving ACR/EULAR remission at week 30
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).
Percentage of participants achieving ACR/EULAR remission at week 18
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).
Percentage of participants achieving ACR/EULAR remission at week 6
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)
Change 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 Criteria Responders every time
Percentage of American College of Rheumatology [ACR] 20 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

First Posted
June 9, 2021
Last Updated
June 17, 2021
Sponsor
Qilu Hospital of Shandong University
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1. Study Identification

Unique Protocol Identification Number
NCT04928066
Brief Title
The Efficacy and Safety of Tofacitinib (TF) With Iguratimod (IGU) on RA
Official Title
Efficacy and Safety of Tofacitinib (TF) Combined With Iguratimod(IGU) in the Treatment of Moderate to Severe Active Rheumatoid Arthritis (RA)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 1, 2020 (Actual)
Primary Completion Date
December 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
RA is a common autoimmune disease that causes joint damage.It is necessary to reach the standard as soon as possible and give effective drugs according to the patient's disease activity to avoid disability. Tofacitinib(TF) is a new type of oral tyrosine kinase inhibitor (JAKi) for the treatment of moderate to severe active RA. However, there is alack of Chinese data on the joint scheme, long-term use, maintenance and stop of TF in the real world. We will use the new JAK combination regimen to treat RA patients, and carry out long-term clinical follow-up for 30 weeks.
Detailed Description
Objective: To observe the clinical efficacy and safety of TF combined with/ without IGU for 30 weeks in patients with moderate to severe active RA with different clinical characteristics and subgroups by using a prospective cohort , and to find the best combination scheme of TF.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
Tofacitinib, Iguratimod

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tofacitinib (TF)+Iguratimod (IGU)
Arm Type
Experimental
Arm Description
Drug: Iguratimod（IGU），25mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Tofacitinib（TF），5mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Prednisone （Pred）： 0-10mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response.
Arm Title
Tofacitinib (TF)
Arm Type
Other
Arm Description
Drug: Tofacitinib（TF），5mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Prednisone （Pred）： 0-10mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response.
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)
Tofacitinib
Other Intervention Name(s)
TF
Intervention Description
Tofacitinib,5mg, 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)
Pred
Other Intervention Name(s)
Prednisone
Intervention Description
Pred, 0-10mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response.
Primary Outcome Measure Information:
Title
The percentage of patients who achieve clinical remission at week 30 using European League Against Rheumatism (EULAR) response criteria DAS28
Description
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.
Time Frame
week 30
Secondary Outcome Measure Information:
Title
The percentage of patients who achieve clinical remission using DAS28-ESR at week 18
Description
The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 18.
Time Frame
week 18
Title
The percentage of patients who achieve clinical remission using DAS28-ESR at week 6
Description
The percentage of patients whose DAS28 achieve remission（DAS28-ESR≤ 2.6）and Low Disease Activity (DAS28-ESR ≤ 3.2) at week 18.
Time Frame
week 6
Title
Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 30
Description
△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.
Time Frame
week 30
Title
Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 18
Description
EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 18. Moderate responders：△DAS28 > 1.2 and still DAS28 > 3.2 at week 18; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 18. Nonresponders：△DAS28 ≤0.6，or DAS28 >5.1 at week 18. DAS28-defined remission was classified as a score of <2.6.
Time Frame
week 18
Title
Percentage of Disease Activity Score 28 (DAS28) -ESR Criteria Responders at week 6
Description
EULAR response states were classified as follows: DAS28-ESR Good responders: △DAS28 > 1.2 and DAS28 ≤3.2 at week 6. Moderate responders：△DAS28 > 1.2 and still DAS28 > 3.2 at week 6; or 1.2 ≥△DAS28 > 0.6 and DAS28 ≤ 5.1 at week 6. Nonresponders：△DAS28 ≤0.6，or DAS28 >5.1 at week 6. DAS28-defined remission was classified as a score of <2.6.
Time Frame
week 6
Title
Percentage of participants achieving ACR/EULAR remission at week 30
Description
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).
Time Frame
week 30
Title
Percentage of participants achieving ACR/EULAR remission at week 18
Description
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).
Time Frame
week 18
Title
Percentage of participants achieving ACR/EULAR remission at week 6
Description
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).
Time Frame
week 6
Title
Change from baseline Simplified Disease Activity Index (SDAI)
Description
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.
Time Frame
up to week 30
Title
Change from baseline Clinical Disease Activity Index (CDAI)
Description
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.
Time Frame
up to week 30
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 30
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 30
Title
Change from baseline Health Assessment Questionnaire Disability Index (HAQ-DI)
Description
Change 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.
Time Frame
up to week 30
Title
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders every time
Description
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders every time
Time Frame
up to week 30
Title
Incidence of participant withdrawal
Description
Percentage of participants who withdraw from this study.
Time Frame
up to week 30
Title
Number of participants with"adverse events (AEs)"
Description
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.
Time Frame
up to week 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who meet the following inclusion criteria will be eligible to participate in the study: Patients who meet RA standards in 1987 and 2010 or ERA standards in 2012; Age > 18 years old; the extrapulmonary manifestations of RA were stable; Patients with NSAIDs tolerance; DAS28-ESR is highergreater than 2.6. Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study: Patients with acute and chronic infection; Platelet count < 80*10^9/L, or white blood cell < 3*10^9/L; ALT or AST is 2 times higher than the upper limit of normal value; Renal insufficiency: serum Cr ≥ 176 umol/L; Pregnant or lactating women (breastfeeding); Have a history of malignant tumor (the cure time is less than 5 years); Patients with severe hypertension and cardiac insufficiency; Other diseases or conditions in which immune suppressants cannot be used; People who are allergic to TF.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qiang Shu, Dr.
Phone
0086-0531-82169654
Email
shuqiang@sdu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaoyan Qi
Phone
0086-0531-82169654
Email
sdqixiaoyan@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaoyun Yang, Dr.
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
Email
qlyykyc@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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The Efficacy and Safety of Tofacitinib (TF) With Iguratimod (IGU) on RA

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