Study To Evaluate The Safety And Efficacy Of ILV-094 In Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety and efficacy of different dose regimens of ILV-094 compared with placebo, administered subcutaneously to subjects with active rheumatoid arthritis who are taking methotrexate.

Official Title
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RANDOMIZED, PARALLEL, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ILV-094 ADMINISTERED SUBCUTANEOUSLY TO SUBJECT WITH RHEUMATOID ARTHRITIS.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Placebo
* Drug: ILV-094
* Drug: ILV-094
* Other: Placebo
* Drug: ILV-094


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the American College of Rheumatology (ACR) 1987 revised criteria for classification of Rheumatoid Arthritis (RA) for at least 6 months prior to screening Active RA at the time of screening and baseline consisting of >= 5 swollen and >= 5 tender joints (28-joint count) and at least 1 of the following at screening: C-reactive protein >= 10 mg/L or Erythrocyte Sedimentation Rate >= 28 mm/h Must be receiving methotrexate for at least 12 weeks, with a stable route and dose (up to 25 mg weekly) for at least 8 weeks prior to the baseline visit. Exclusion Criteria: Subjects with other rheumatic diseases Cancer or history of cancer (other than cutaneous basal cell carcinoma and squamous cell carcinoma or in situ cervical cancer) Any prior use of B cell-depleting therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1<br>Part 1: Placebo | Other: Placebo<br>* Part 1: Placebo SC administration every 2 weeks X 10 weeks.<br>|
| Experimental: Arm 2<br>Part 1: 100 mg ILV-094 SC Q4W | Drug: ILV-094<br>* Part 1: ILV-094 100 mg SC every 4 weeks (alternating ILV-094 100 mg and placebo every 2 weeks) X 10 weeks.<br>|
| Experimental: Arm 3<br>Part 1: 100 mg ILV-094 SC Q2W | Drug: ILV-094<br>* Part 1: ILV-094 100 mg SC every 2 weeks X 10 weeks.<br>|
| Placebo Comparator: Arm 4<br> | Other: Placebo<br>* Part 2: Placebo SC administration every 2 weeks X 10 weeks<br>|
| Experimental: Arm 5<br>Part 2: 200 mg ILV-094 SC Q2W | Drug: ILV-094<br>* Part 2: ILV-094 200 mg SC every 2 weeks X 10 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an American College of Rheumatology 20 Percent (ACR20) Response at Week 12 | ACR20 response: greater than or equal to (>=) 20 percent improvement in tender joint count; >=20 percent improvement in swollen joint count; and >=20 percent improvement in 3 of 5 remaining ACR core measures: participant's global assessment of disease activity (score: 0 [very well] to 10 [worst]); participant's assessment of pain (score: 0 [very well] to 100 [extremely bad]); physician global assessment of disease activity (score: 0 [very well] to 10 [worst]); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]) (score: 0 [no difficulty] to 3 [unable to do]); and C-reactive protein (CRP). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an American College of Rheumatology 20 Percent (ACR20) Response at Week 2, 4, 6, 8 and 10 | ACR20 response: >=20 percent improvement in tender joint count; >=20 percent improvement in swollen joint count; and >=20 percent improvement in 3 of 5 remaining ACR core measures: participant's global assessment of disease activity (score: 0 [very well] to 10 [worst]); participant's assessment of pain (score: 0 [very well] to 100 [extremely bad]); physician global assessment of disease activity (score: 0 [very well] to 10 [worst]); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]) (score: 0 [no difficulty] to 3 [unable to do]); and C-reactive protein (CRP). | Week 2, 4, 6, 8, 10 | 
| Percentage of Participants With an American College of Rheumatology 50 Percent (ACR50) Response at Week 2, 4, 6, 8, 10 and 12 | ACR50 response: >=50 percent improvement in tender joint count; >=50 percent improvement in swollen joint count; and 50 improvement in 3 of 5 remaining ACR core measures: participant's global assessment of disease activity (score: 0 [very well] to 10 [worst]); participant's assessment of pain (score: 0 [very well] to 100 [extremely bad]); physician global assessment of disease activity (score: 0 [very well] to 10 [worst]); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]) (score: 0 [no difficulty] to 3 [unable to do]); and C-reactive protein (CRP). | Week 2, 4, 6, 8, 10, 12 | 
| Percentage of Participants With an American College of Rheumatology 70 Percent (ACR70) Response at Week 2, 4, 6, 8, 10 and 12 | ACR70 response:>=70 percent improvement in tender joint count; >=70 percent improvement in swollen joint count; and 70 percent improvement in 3 of 5 remaining ACR core measures: participant's global assessment of disease activity (score: 0 [very well] to 10 [worst]); participant's assessment of pain (score: 0 [very well] to 100 [extremely bad]); physician global assessment of disease activity (score: 0 [very well] to 10 [worst]); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]) (score: 0 [no difficulty] to 3 [unable to do]); and C-reactive protein (CRP). | Week 2, 4, 6, 8, 10, 12 | 
| Disease Activity Score Based on 28-Joints Count (DAS28) Using C-Reactive Protein (CRP) | DAS28 (CRP) was calculated from number of swollen joints and tender joints using the 28 joints count; CRP (milligram/Liter [mg/L]); and general health visual analog scale (VAS) score (participant rated scale with scores ranging from 0mm [very well] to 100mm [extremely bad]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 (CRP) less than or equal to (<=) 3.2 implied low disease activity, greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and less than (<) 2.6 implied remission. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| Disease Activity Score Based on 28-Joints Count (DAS28) Using Erythrocyte Sedimentation Rate (ESR) | DAS28 (ESR) was calculated from the number of swollen joints and tender joints using the 28 joints count; ESR (millimeters per hour [mm/hour]); and general health VAS score (participant rated scale with scores ranging from 0 [very well] to 100 [extremely bad]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 (ESR) <=3.2 implied low disease activity, >3.2 to 5.1 implied moderate to high disease activity, and <2.6 implied remission. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| Tender Joints Counts (TJC) | Number of tender joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| Swollen Joints Count (SJC) | Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| Physician Global Assessment of Disease Activity | Physician global assessment of disease activity was measured on an 11-point scale, ranging from 0 to 10, where 0 = no disease activity and 10 = extreme disease activity. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| Participant Global Assessment of Disease Activity | Participants answered: considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a scale ranging from 0 to 10, where 0 = no disease activity and 10 = extreme disease activity. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| Pain Visual Analog Scale (VAS) | Participants assessed the amount of pain currently experienced by them on a 100 millimeter (mm) VAS ranging from 0= no pain to 100= severe pain. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| General Health Visual Analog Scale (VAS) | General health VAS is a 100 mm line marked by the participant. Participants were asked, In general how would you rate your health currently concerning the arthritis? Scores ranged from 0 mm = very well to 100 mm = extremely bad. | Baseline, Week 2, 4, 6, 8, 10, 12 | 
| Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Health assessment questionnaire-disability index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to perform activity. Overall score was 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. | Baseline, Week 4, 2, 6, 8, 10, 12 | 
| 36-Item Short-Form Health Survey (SF-36) | SF-36 is a standardized survey consisting of 36 items summarized into 8 multi-item scales evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality and mental health. Two summary scores, the physical component summary (PCS) and the mental component summary (MCS) derived are derived by aggregating the 8 aspects. The score for each aspect and physical and mental component summary are scaled 0-100 where, higher score indicating highest level of functioning. | Baseline, Week 4, 8, 12 | 
| Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale | FACIT-fatigue is a 13-item questionnaire. Participants score each item on a 5-point scale ranging from 0 (not at all) to 4 (very much). The scoring algorithm is such that the item responses are reversed in score (except for 2 items, I have energy and I am able to do my usual activities), in order to reflect higher scores as less fatigue. The sum of all responses resulted in the FACIT-fatigue total score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status. | Baseline, Week 4, 8, 12 | 
| Number of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28 | DAS28-based EULAR response criteria was 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. | Week 2, 4, 6, 8, 10, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, ACR, Methotrexate, Interleukin-22