Efficacy and Safety of BIIL 284 BS in Adult Patients With Active Rheumatoid Arthritis
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
BIIL 284 BS low dose
BIIL 284 BS medium dose
BIIL 284 BS high dose
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid
Eligibility Criteria
Inclusion Criteria:
- Patients of >=18 and <= 70 years of age
Patients suffering from rheumatoid arthritis as defined by the American Rheumatism Association (ARA) criteria revised 1987 and date of diagnosis >= 6 months. At least 4 of the following 7 criteria must be present:
- Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement for at least 6 weeks
- Arthritis (soft tissue thickening or fluid - not bony overgrowth alone) of at least 3 joint areas for at least 6 weeks
- Arthritis of hand joints (at least one area swollen in a wrist, metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint) for at least 6 weeks
- Symmetrical arthritis (observed by a physician) with simultaneous involvement of the joints on both sides of the body for at least 6 weeks
- Rheumatoid nodules (observed by a physician) over bony prominence or extensor surfaces or in juxta-articular regions
- Serum rheumatoid factor positive
- X-ray changes typical of rheumatoid arthritis (erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints)
- Patients belonging to the RA functional class I, II or III
Active RA as defined at visit 2 by:
- Swollen joint count at least of 6 (of 28 joints examined) and
- Tender joint count at least of 8 (of 28 joints examined) and
Patients must fulfil 2 out of the 3 following criteria:
- Patient's assessment of pain (VAS) >= 40 mm
- Investigator's global assessment of disease activity on a VAS >= 40 mm
- ESR >= 28 mm/h or CRP >= 20 mg/L
- Patient's written informed consent obtained at Visit 1 (screening) before enrolment in the study
Exclusion Criteria:
- Patient presenting or having a history of inflammatory rheumatic disease other than RA (e.g.: mixed connective tissue disease, systemic lupus erythematosus, seronegative spondyloarthropathy)
- Patients who have failed to more than 3 different disease-modifying antirheumatic drug (DMARDs) therapies previously due to lack of efficacy (in case of combined therapy each DMARDs used is counted as one)
- Patients with any other disease that could interfere with the evaluation of efficacy and safety
Patients in treatment with any DMARDs / slow-acting anti-rheumatic drug (SAARDs) during the periods specified:
- 4 weeks before V2: Methotrexate, parenteral/oral gold, D-penicillamine, Sulphasalazine, antimalarials (e.g.:Chloroquine/Hydroxychloroquine), Azathioprine, Cyclosporine A, Alkylating agents (e.g.: Cyclophosphamide / Chlorambucil), Minocycline, Etanercept (Enbrel®), and Leflunomide (only if wash-out with Colestyramine has been done after leflunomide discontinuation)
- 3 months before Visit 2: Leflunomide if no wash- out with colestyramine has been done after leflunomide discontinuation, Infliximab (Remicade®), any other biological compound.
- Patient in treatment with oral corticosteroids at a dose higher than 10 mg/day or 0.2 mg/Kg/day (prednisone equivalent) whichever is lower, during the 4 weeks prior to Visit 2, change in the treatment with oral corticosteroids during the 4 weeks prior to Visit 2 or intended change during the trial
- Patients in treatment with any parenteral (intravenous, intramuscular or intraarticular) treatment with corticosteroids during the 4 weeks prior to Visit 2 or their intended use during the trial.
- Change in treatment with non-steroidal anti-inflammatory drugs (NSAIDs) during the 2 weeks prior to Visit 2 or any intended change during the trial.
- Synovectomy, and/or surgical treatment for RA in the previous 3 months prior to visit 2 or intended indication during the trial.
- Synoviorthesis in the previous 4 weeks prior to Visit 2 or intended indication during the trial.
- Patients in treatment with any other leukotriene inhibitors such as montelukast or zafirlukast 4 weeks prior to Visit 2 or intended use during the trial.
- Initiation of physiotherapy during the 2 weeks before V2, or intended change during the trial
- Patients with history of cardiovascular, renal, neurologic, psychiatric, liver, gastrointestinal (including lactose intolerance ), immunologic or endocrine dysfunction if they are clinically significant.
- Patients with any other known condition or circumstance, which would in the investigator's opinion, prevents compliance or completion of the study
- Patients with history of cancer within the past 5 years, excluding treated basal cell carcinoma
- Patients with chronic infection or acute infections during the 4 weeks before visit 1
- Patients with known positive serology for hepatitis B or C
- Patients with anticoagulant treatment (i.e. dicumarol or derivatives, warfarin)
Any of the following abnormal laboratory parameters at Visit 2:
- Impaired hepatic function, defined by serum levels of either Aspartate Aminotransferase (AST)(SGOT), Alanine Aminotransferase (ALT) (SGPT), alkaline phosphatase or bilirubin > 2 x upper limit of normal (ULN)
- Impaired renal function, defined by serum creatinine > 133 mmol/L (1.5 mg/dl)
- Hemoglobin values < 10 g/dl
- White blood cell count <= 3.500 cells/mm3
- Platelet count of less than 120.000/mm3
- Severe hypoproteinemia (e.g. in case of severe liver disease or nephrotic syndrome) with albumin < 3.0 g/dl
- Patients with any other abnormal, clinically relevant laboratory values not related to RA
- Patients participating in another clinical trial during the 3 months prior to visit 2
- Previous participation in the randomised period of this study
- Patients with a significant history and/or active alcohol or drug abuse Significant is defined as that which in the opinion of the investigator may either put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study
- Pregnancy (to be excluded by pregnancy test at visit 1) or breast feeding, and sexually active women with childbearing potential not using a medically approved method of contraception (i.e. oral contraceptives, intrauterine devices, or double-barrier) for at least one month before and throughout the study period
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
BIIL 284 BS low dose
BIIL 284 BS medium dose
BIIL 284 BS high dose
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Percentage of patients achieving 20% improvement assessed by the American College of Rheumatology (ACR) criteria (ACR20)
Secondary Outcome Measures
Percentage of patients achieving 50% improvement (ACR50)
Number of withdrawals due to lack of efficacy
Number of swollen joints
Number of tender joints
Patient's assessment of pain on a visual analog scale (VAS)
Patient's global assessment of disease activity by VAS
Investigator's global assessment of disease activity by VAS
Patient's assessment of physical function
via Health Assessment Questionnaire (HAQ)
Change in erythrocyte sedimentation rate (ESR)
Change in C-reactive protein (CRP)
Change in Quality of Life
assessed by the SF-36 questionnaire
Change in Disease Activity Score (DAS 28)
Disease Activity Score in 28-joint count
Change in duration of morning stiffness
Consumption of rescue medication
Number of patients with adverse events
Number of withdrawals due to adverse events
Final global assessment of tolerability by investigator on a 4-point scale
Patient's assessment of fatigue by VAS
Number of patients with clinically significant changes in laboratory findings
Number of patients with clinically significant changes in vital signs
Number of patients with clinically significant changes in 12-lead ECG
Full Information
NCT ID
NCT02251210
First Posted
September 25, 2014
Last Updated
September 25, 2014
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02251210
Brief Title
Efficacy and Safety of BIIL 284 BS in Adult Patients With Active Rheumatoid Arthritis
Official Title
Three Month, Randomised, Double-blind, Double-dummy, Placebo-controlled, Multiple Dose-range Study of the Efficacy and Safety of BIIL 284 BS (5, 25 and 75 mg p.o. Once Daily) in Adult Patients With Active Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
May 2001 (undefined)
Primary Completion Date
November 2002 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
To investigate efficacy and safety of 3 doses of BIIL 284 BS in active rheumatoid arthritis (RA) and determine the dose with most positive efficacy / safety ratio. Pharmacokinetic profile will be also obtained.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
404 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BIIL 284 BS low dose
Arm Type
Experimental
Arm Title
BIIL 284 BS medium dose
Arm Type
Experimental
Arm Title
BIIL 284 BS high dose
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BIIL 284 BS low dose
Intervention Type
Drug
Intervention Name(s)
BIIL 284 BS medium dose
Intervention Type
Drug
Intervention Name(s)
BIIL 284 BS high dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Percentage of patients achieving 20% improvement assessed by the American College of Rheumatology (ACR) criteria (ACR20)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Percentage of patients achieving 50% improvement (ACR50)
Time Frame
3 months
Title
Number of withdrawals due to lack of efficacy
Time Frame
up to 3 months
Title
Number of swollen joints
Time Frame
up to 3 months
Title
Number of tender joints
Time Frame
up to 3 months
Title
Patient's assessment of pain on a visual analog scale (VAS)
Time Frame
up to 3 months
Title
Patient's global assessment of disease activity by VAS
Time Frame
up to 3 months
Title
Investigator's global assessment of disease activity by VAS
Time Frame
up to 3 months
Title
Patient's assessment of physical function
Description
via Health Assessment Questionnaire (HAQ)
Time Frame
up to 3 months
Title
Change in erythrocyte sedimentation rate (ESR)
Time Frame
up to 3 months
Title
Change in C-reactive protein (CRP)
Time Frame
up to 3 months
Title
Change in Quality of Life
Description
assessed by the SF-36 questionnaire
Time Frame
baseline, 3 months
Title
Change in Disease Activity Score (DAS 28)
Description
Disease Activity Score in 28-joint count
Time Frame
baseline, up to 3 months
Title
Change in duration of morning stiffness
Time Frame
up to 3 months
Title
Consumption of rescue medication
Time Frame
up to 3 months
Title
Number of patients with adverse events
Time Frame
up to 3 months
Title
Number of withdrawals due to adverse events
Time Frame
up to 3 months
Title
Final global assessment of tolerability by investigator on a 4-point scale
Time Frame
3 months
Title
Patient's assessment of fatigue by VAS
Time Frame
up to 3 months
Title
Number of patients with clinically significant changes in laboratory findings
Time Frame
up to 3 months
Title
Number of patients with clinically significant changes in vital signs
Time Frame
up to 3 months
Title
Number of patients with clinically significant changes in 12-lead ECG
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients of >=18 and <= 70 years of age
Patients suffering from rheumatoid arthritis as defined by the American Rheumatism Association (ARA) criteria revised 1987 and date of diagnosis >= 6 months. At least 4 of the following 7 criteria must be present:
Morning stiffness in and around the joints lasting at least 1 hour before maximal improvement for at least 6 weeks
Arthritis (soft tissue thickening or fluid - not bony overgrowth alone) of at least 3 joint areas for at least 6 weeks
Arthritis of hand joints (at least one area swollen in a wrist, metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint) for at least 6 weeks
Symmetrical arthritis (observed by a physician) with simultaneous involvement of the joints on both sides of the body for at least 6 weeks
Rheumatoid nodules (observed by a physician) over bony prominence or extensor surfaces or in juxta-articular regions
Serum rheumatoid factor positive
X-ray changes typical of rheumatoid arthritis (erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints)
Patients belonging to the RA functional class I, II or III
Active RA as defined at visit 2 by:
Swollen joint count at least of 6 (of 28 joints examined) and
Tender joint count at least of 8 (of 28 joints examined) and
Patients must fulfil 2 out of the 3 following criteria:
Patient's assessment of pain (VAS) >= 40 mm
Investigator's global assessment of disease activity on a VAS >= 40 mm
ESR >= 28 mm/h or CRP >= 20 mg/L
Patient's written informed consent obtained at Visit 1 (screening) before enrolment in the study
Exclusion Criteria:
Patient presenting or having a history of inflammatory rheumatic disease other than RA (e.g.: mixed connective tissue disease, systemic lupus erythematosus, seronegative spondyloarthropathy)
Patients who have failed to more than 3 different disease-modifying antirheumatic drug (DMARDs) therapies previously due to lack of efficacy (in case of combined therapy each DMARDs used is counted as one)
Patients with any other disease that could interfere with the evaluation of efficacy and safety
Patients in treatment with any DMARDs / slow-acting anti-rheumatic drug (SAARDs) during the periods specified:
4 weeks before V2: Methotrexate, parenteral/oral gold, D-penicillamine, Sulphasalazine, antimalarials (e.g.:Chloroquine/Hydroxychloroquine), Azathioprine, Cyclosporine A, Alkylating agents (e.g.: Cyclophosphamide / Chlorambucil), Minocycline, Etanercept (Enbrel®), and Leflunomide (only if wash-out with Colestyramine has been done after leflunomide discontinuation)
3 months before Visit 2: Leflunomide if no wash- out with colestyramine has been done after leflunomide discontinuation, Infliximab (Remicade®), any other biological compound.
Patient in treatment with oral corticosteroids at a dose higher than 10 mg/day or 0.2 mg/Kg/day (prednisone equivalent) whichever is lower, during the 4 weeks prior to Visit 2, change in the treatment with oral corticosteroids during the 4 weeks prior to Visit 2 or intended change during the trial
Patients in treatment with any parenteral (intravenous, intramuscular or intraarticular) treatment with corticosteroids during the 4 weeks prior to Visit 2 or their intended use during the trial.
Change in treatment with non-steroidal anti-inflammatory drugs (NSAIDs) during the 2 weeks prior to Visit 2 or any intended change during the trial.
Synovectomy, and/or surgical treatment for RA in the previous 3 months prior to visit 2 or intended indication during the trial.
Synoviorthesis in the previous 4 weeks prior to Visit 2 or intended indication during the trial.
Patients in treatment with any other leukotriene inhibitors such as montelukast or zafirlukast 4 weeks prior to Visit 2 or intended use during the trial.
Initiation of physiotherapy during the 2 weeks before V2, or intended change during the trial
Patients with history of cardiovascular, renal, neurologic, psychiatric, liver, gastrointestinal (including lactose intolerance ), immunologic or endocrine dysfunction if they are clinically significant.
Patients with any other known condition or circumstance, which would in the investigator's opinion, prevents compliance or completion of the study
Patients with history of cancer within the past 5 years, excluding treated basal cell carcinoma
Patients with chronic infection or acute infections during the 4 weeks before visit 1
Patients with known positive serology for hepatitis B or C
Patients with anticoagulant treatment (i.e. dicumarol or derivatives, warfarin)
Any of the following abnormal laboratory parameters at Visit 2:
Impaired hepatic function, defined by serum levels of either Aspartate Aminotransferase (AST)(SGOT), Alanine Aminotransferase (ALT) (SGPT), alkaline phosphatase or bilirubin > 2 x upper limit of normal (ULN)
Impaired renal function, defined by serum creatinine > 133 mmol/L (1.5 mg/dl)
Hemoglobin values < 10 g/dl
White blood cell count <= 3.500 cells/mm3
Platelet count of less than 120.000/mm3
Severe hypoproteinemia (e.g. in case of severe liver disease or nephrotic syndrome) with albumin < 3.0 g/dl
Patients with any other abnormal, clinically relevant laboratory values not related to RA
Patients participating in another clinical trial during the 3 months prior to visit 2
Previous participation in the randomised period of this study
Patients with a significant history and/or active alcohol or drug abuse Significant is defined as that which in the opinion of the investigator may either put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study
Pregnancy (to be excluded by pregnancy test at visit 1) or breast feeding, and sexually active women with childbearing potential not using a medically approved method of contraception (i.e. oral contraceptives, intrauterine devices, or double-barrier) for at least one month before and throughout the study period
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
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Efficacy and Safety of BIIL 284 BS in Adult Patients With Active Rheumatoid Arthritis
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