An Efficacy and Safety Study of Infliximab in Participants With Rheumatoid Arthritis

A Multi-Center, Pre-Marketing Clinical Trial to Evaluate the Efficacy and Safety of Infliximab Treatment on Rheumatoid Arthritis

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00896168

Enrollment

234

Registered

2009-05-11

Start date

2007-06-30

Completion date

2008-04-30

Last updated

2013-09-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Arthritis, Rheumatoid

Keywords

Arthritis, Rheumatoid, Infliximab, Methotrexate

Brief summary

The purpose of this study is to compare the effectiveness of iInfliximab plus methotrexate (MTX) in treatment of Rheumatoid rheumatoid Arthritis arthritis (RA) (it is an autoimmune disease that causes pain, swelling, stiffness and loss of function in joints) in participants with moderate disease versus participants with severe disease and to compare the efficacy and safety of the MTX subgroups.

Detailed description

This is an open-label (all people know the identity of the intervention), multi-center (study conducted in more than 1 center), prospective (study following participants forward in time) study comparing the American College of Rheumatology (ACR) scores of participants with moderate RA (defined as having a score greater than 3.2, but less than 5.1 on the Disease Activity Score 28 \[DAS 28\]) to those participants with severe RA (defined as having a score greater than 5.1 on the DAS 28 score) disease while being treated with infliximab and MTX. DAS evaluates RA activity by several parameters including the number of swollen and tender joints and the participant's own assessment of their pain. Participants will receive infliximab 3 milligram (mg) per kilogram (kg) intravenous infusion (drug given into a vein) (over no less than 2 hours) at Weeks 0, 2, 6, 14 and 22 along oral MTX in a stable dose of 7.5 to 20 mg per week (equal to the dose used before participation in the study) for 22 Weeks. Participants will have a follow-up visit on Week 26. Efficacy will primarily be assessed by the percentage of participants obtaining ACR20, ACR50 and ACR70 response at Week 26. Participants' safety will be assessed throughout the study.

Interventions

DRUGInfliximab

Infliximab 3 mg per kg intravenous infusion at Week 0, 2, 6, 14 and 22.

DRUGMethotrexate

MTX stable dose (7.5 to 20 mg/week equal to the dose used before participation in the study) for 22 weeks.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Participants who have a definitive diagnosis of rheumatoid arthritis (RA) based on the American College of Rheumatology Criteria 1987 * Participants must have been on Methotrexate (MTX) for 12 weeks at the stable dose for at least 4 weeks * Participants using oral corticosteroids, must have been on a stable dose of prednisone less than 10 milligram per day (mg/day) or its equivalent for at least 4 weeks before screening or if currently not using corticosteroids, the participant must not have received corticosteroids for at least 4 weeks before screening * Participants with moderate to severe RA (Disease Activity Score \[DAS28\] greater than 3.2) * Male participants shall adopt contraceptive measures during the trial and within 6 months after the completion of trial (such as spermicidal barrier), or their female sexual partners shall agree to adopt effective contraceptive measures during the trial or within 6 months after the completion of trial (such as oral contraceptives, contraceptives for injection, intrauterine device \[IUD\], or sterilization by surgery); female participants of childbearing potential with negative urine pregnancy test upon enrollment in addition to adopting the said contraceptive measures

Exclusion criteria

* Participant who has a known allergy to human immunoglobulin proteins or other components of infliximab * Participant who has a history of receiving infliximab or any other biological preparations * Participant who is in stage IV RA evaluated by X-ray * Participants suffering from tuberculosis * Female participant or male participant's wife who plans to become pregnant during this study and within 6 months after completion of this study

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving American College of Rheumatology Score 20 Percent (ACR20) Response	Week 26	ACR20 is achieved if the participant has 20% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire \[HAQ\]) and C-reactive protein (CRP).
Percentage of Participants Achieving American College of Rheumatology Score 50 Percent (ACR50) Response	Week 26	ACR50 is achieved if the participant has 50% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire \[HAQ\]) and C-reactive protein (CRP).
Percentage of Participants Achieving American College of Rheumatology Score 70 Percent (ACR70) Response	Week 26	ACR70 is achieved if the participant has 70% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire \[HAQ\]) and C-reactive protein (CRP).

Secondary

Measure	Time frame	Description
Change From Baseline in Participants' Global Disease Assessment at Week 26	Baseline and Week 26	Participants scored the overall disease state using VAS of 0-100 mm. Participants might have assessed the Control of their current disease using 0 mm=very good to 100 mm=very poor scale.
Change From Baseline in Physicians' Global Disease Assessment at Week 26	Baseline and Week 26	Physicians scored the overall disease state using VAS of 0-100 mm. Physicians might have assessed the activity of RA using 0=no active RA to 100=most serious active RA scale.
Change From Baseline in Duration of Morning Stiffness at Week 26	Baseline and Week 26	Duration of morning stiffness: Time elapsed in minutes when participant woke up in morning and was able to resume normal activities without stiffness. Increase in stiffness duration from Baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.
Change From Baseline in Swollen Joints Count at Week 26	Baseline and Week 26	Number of swollen joints were determined by examination of 28 joints and identifying when swelling is present. The number of swollen joints was recorded on the joint assessment form at each visit; the swelling was graded on a scale ranging from 0-2 (0=no swelling, 1=swelling, but bony landmarks seen, 2=swelling but bone marks not seen). Participants categorized as Hepatitis B Virus antigen (HBsAb) positive/negative (at least 1 of HbsAg, HBeAg, Anti-HbeAg and Anti-HbcAg were positive or all were negative).
Change From Baseline in C-Reactive Protein (CRP) at Week 26	Baseline and Week 26	CRP is a protein found in the blood, the levels of which rise in response to inflammation.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 26	Baseline and Week 26	ESR is also called a sedimentation rate or Westergren ESR, is the rate at which red blood cells sediment in a period of 1 hour. It is a common hematology test, and is a non-specific measure of inflammation.
Change From Baseline in Health Assessment Questionnaire (HAQ) at Week 26	Baseline and Week 26	The HAQ, a 20-question instrument, assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each area are scored from 0=no difficulty to 3=inability to perform a task in that area.
Change From Baseline in Tender Joints Count at Week 26	Baseline and Week 26	Number of tender joints was determined by examination of 28 joints and identifying when tenderness is present. The number of tender joints was recorded on the joint assessment form at each visit; the tenderness of symptomatic joints was graded on a scale ranging from 0-3 (0=no pain, 1=mild, 2= moderate and 3=severe).
Change From Baseline in Participant's Pain Visual Analogue Scale (VAS) Score at Week 26	Baseline and Week 26	Participant's pain was assessed on VAS of 0 to 100 mm (0=not at all to 100=extreme pain).

Participant flow

Participants by arm

Arm	Count
Infliximab + Methotrexate (Moderate RA) Participants with moderate RA (score greater than 3.2, but less than 5.1 on the DAS 28) received infliximab 3 mg/kg intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) at Week 0, 2, 6, 14 and 22 along with oral MTX in a stable dose of 7.5 to 20 mg per week (equal to the dose used before participation in the study) for 22 weeks.	104
Infliximab + Methotrexate (Severe RA) Participants with severe RA (score greater than 5.1 on the DAS 28) received infliximab 3 mg/kg intravenous infusion at Week 0, 2, 6, 14 and 22 along with oral MTX in a stable dose of 7.5 to 20 mg per week equal to the dose used before participation in the study) for 22 weeks.	130
Total	234

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	7
Overall Study	Lost to Follow-up	1	1
Overall Study	Other	1	1
Overall Study	Treatment failure	8	10

Baseline characteristics

Characteristic	Infliximab + Methotrexate (Moderate RA)	Infliximab + Methotrexate (Severe RA)	Total
Age Continuous	42.83 Years STANDARD_DEVIATION 12.05	46.62 Years STANDARD_DEVIATION 11.39	44.92 Years STANDARD_DEVIATION 11.84
Sex: Female, Male Female	92 Participants	116 Participants	208 Participants
Sex: Female, Male Male	12 Participants	14 Participants	26 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	57 / 104	80 / 130
serious Total, serious adverse events	2 / 104	2 / 130

Outcome results

Primary

Percentage of Participants Achieving American College of Rheumatology Score 20 Percent (ACR20) Response

ACR20 is achieved if the participant has 20% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire \[HAQ\]) and C-reactive protein (CRP).

Time frame: Week 26

Population: Full analysis set (FAS) included participants who received at least 1 dose of study medication and had post efficacy data.

Arm	Measure	Value (NUMBER)
Infliximab + Methotrexate (Moderate RA)	Percentage of Participants Achieving American College of Rheumatology Score 20 Percent (ACR20) Response	63.46 Percentage of participants
Infliximab + Methotrexate (Severe RA)	Percentage of Participants Achieving American College of Rheumatology Score 20 Percent (ACR20) Response	76.15 Percentage of participants

Primary

Percentage of Participants Achieving American College of Rheumatology Score 50 Percent (ACR50) Response

ACR50 is achieved if the participant has 50% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire \[HAQ\]) and C-reactive protein (CRP).

Time frame: Week 26

Population: The FAS population included participants who received at least 1 dose of study medication and had post efficacy data.

Arm	Measure	Value (NUMBER)
Infliximab + Methotrexate (Moderate RA)	Percentage of Participants Achieving American College of Rheumatology Score 50 Percent (ACR50) Response	47.12 Percentage of participants
Infliximab + Methotrexate (Severe RA)	Percentage of Participants Achieving American College of Rheumatology Score 50 Percent (ACR50) Response	57.69 Percentage of participants

Primary

Percentage of Participants Achieving American College of Rheumatology Score 70 Percent (ACR70) Response

ACR70 is achieved if the participant has 70% improvement from Baseline in swollen joint count; tender joint count and in at least 3 of the following 5 assessments: participants' assessment of pain; participants' global assessment of disease activity; physician's global assessment of disease activity; participants' assessment of physical function (Health Assessment Questionnaire \[HAQ\]) and C-reactive protein (CRP).

Time frame: Week 26

Population: The FAS population included participants who received at least 1 dose of study medication and had post efficacy data.

Arm	Measure	Value (NUMBER)
Infliximab + Methotrexate (Moderate RA)	Percentage of Participants Achieving American College of Rheumatology Score 70 Percent (ACR70) Response	29.81 Percentage of participants
Infliximab + Methotrexate (Severe RA)	Percentage of Participants Achieving American College of Rheumatology Score 70 Percent (ACR70) Response	29.23 Percentage of participants

Secondary