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Study Evaluating 2 Dosing Regimens Of TRU-015 In Rheumatoid Arthritis

Phase 2
Terminated
Conditions
Arthritis, Rheumatoid
Interventions
Registration Number
NCT00634933
Lead Sponsor
Pfizer
Brief Summary

This study will evaluate the efficacy and safety of two dosing regimens of a compound known as TRU-015 in combination with methotrexate (MTX) in patients with active rheumatoid arthritis.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
222
Inclusion Criteria
  • Clinical diagnosis of active seropositive rheumatoid arthritis on a stable dose of methotrexate (7.5-25 mg weekly) for at least 12 weeks with or without a history of anti-TNF use.
Exclusion Criteria
  • Any prior use of rituximab or other B cell depleting agents.
  • Any significant health problem other than rheumatoid arthritis
  • Clinically significant laboratory abnormalities

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2PrednisoneConsists of Arms 2a and 2b
Arm 2TRU-015Consists of Arms 2a and 2b
Arm 1TRU-015Consists of Arms 1a and 1b
Arm 1MethylprednisoloneConsists of Arms 1a and 1b
Arm 1PrednisoneConsists of Arms 1a and 1b
Arm 3PrednisoneConsists of Arms 3a and 3b.
Arm 3TRU-015Consists of Arms 3a and 3b.
Arm 2MethylprednisoloneConsists of Arms 2a and 2b
Arm 3MethylprednisoloneConsists of Arms 3a and 3b.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With an American College of Rheumatology 50% (ACR 50) Response at Week 24Week 24

ACR50 response: greater than or equal to (\>=) 50 percent (%) improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ-DI\]); and C-Reactive Protein (CRP).

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With an American College of Rheumatology 20% (ACR20) ResponseWeek 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ACR20 response: \>= 20% improvement in tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP.

Percentage of Participants With an American College of Rheumatology 50% (ACR50) ResponseWeek 2, 4, 8, 12, 16, 20, 28, 32, 36, 40, 44, 48, 52

ACR50 response: \>=50% improvement in tender joint count; \>=50% improvement in swollen joint count; and \>=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP.

Percentage of Participants With an American College of Rheumatology 70% (ACR70) ResponseWeek 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

ACR70 response: \>=70% improvement in tender joint count; \>=70% improvement in swollen joint count; and \>=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (HAQ-DI); and CRP.

Number of Tender JointsBaseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

The number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1.

Number of Swollen JointsBaseline. Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

The number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.

Duration of Morning StiffnessBaseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Duration of morning stiffness is defined as the time elapsed when participant woke up in the morning and was able to resume normal activities without stiffness in minutes (if none was present = 0; if morning stiffness was continuing, average of duration of stiffness over the past 3 days was reported; if stiffness persisted the entire day, 1440 minutes \[24 hours\*60 minutes\] was recorded).

Visual Analogue Scale for Pain (VAS-pain)Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

100 millimeter (mm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 = no pain to 100 = worst possible pain.

Physician Global Assessment (PGA) of Disease ActivityBaseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Physician Global Assessment of Disease Activity was measured on a 0 to 10 point scale, where 0 = no disease activity and 10 = extreme disease activity.

Patient Global Assessment (PtGA) of Disease ActivityBaseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Measured using a 0-10 point scale, where 0 = no disease activity and 10 = extreme disease activity.

General Health Visual Analog Scale (VAS)Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

100 mm line (VAS) marked by participant. Participants were asked, "How do you feel concerning your arthritis?" Total possible score range, 0 mm = very well to 100 mm = extremely bad.

Health Assessment Questionnaire Disability Index (HAQ-DI)Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

HAQ-DI: participant-reported assessment of ability to perform tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) hygiene; and 8) common activities over past week. Each item scored on 4-point Likert scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. The overall disability index computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Disease Activity Score Based on 28-joints Count (DAS28)Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and participant's general health visual analog scale (scores ranging 0 \[very well\] to 100 mm \[extremely bad\]). DAS28 less than or equal to (=\<) 3.2 = low disease activity, DAS28 greater than (\>) 3.2 to 5.1 = moderate to high disease activity.

36-Item Short-Form Health Survey (SF-36)Baseline, Week 12, 24, 36, 52

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Euro Quality of Life (EQ-5D)- Health State Profile Utility ScoreBaseline, Week 12, 24, 36, 52

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula developed by EuroQol Group assigns utility value for each domain in the profile. Score is transformed and results in total score range -0.594 to 1.000; higher score indicates a better health state.

Euro Quality of Life (EQ-5D)- Visual Analog Scale (VAS)Baseline, Week 12, 24, 36, 52

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.

Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) ScoreBaseline, Week 12, 24, 36, 52

FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI-RA) ScoreBaseline, Week 12, 24, 36, 52

WPAI-RA consisted of 6 items, a binary question on current employment, 3 questions on hours of work and work-loss, and 2 questions based on 0-10 point scale to judge how RA affects productivity at work and outside of work (0 = no effect on work and 10 = completely prevented from working). Four scores are derived: percent work time missed due to health, percent impairment while working due to health, percent overall work impairment due to health and percent activity impairment due to health. Total possible score range: 0 to 100, where 0 = no impairment and 100 = completely impaired.

Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇷🇸

Niska Banja, Serbia

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