Efficacy and Safety of BIIL 284 BS in Adult Patients With Active Rheumatoid Arthritis

September 25, 2014 updated by: Boehringer Ingelheim

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

404

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Experimental: BIIL 284 BS low dose
Experimental: BIIL 284 BS medium dose
Experimental: BIIL 284 BS high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of patients achieving 20% improvement assessed by the American College of Rheumatology (ACR) criteria (ACR20)
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events
Time Frame: up to 3 months
up to 3 months
Percentage of patients achieving 50% improvement (ACR50)
Time Frame: 3 months
3 months
Number of withdrawals due to lack of efficacy
Time Frame: up to 3 months
up to 3 months
Number of swollen joints
Time Frame: up to 3 months
up to 3 months
Number of tender joints
Time Frame: up to 3 months
up to 3 months
Patient's assessment of pain on a visual analog scale (VAS)
Time Frame: up to 3 months
up to 3 months
Patient's global assessment of disease activity by VAS
Time Frame: up to 3 months
up to 3 months
Investigator's global assessment of disease activity by VAS
Time Frame: up to 3 months
up to 3 months
Patient's assessment of physical function
Time Frame: up to 3 months
via Health Assessment Questionnaire (HAQ)
up to 3 months
Change in erythrocyte sedimentation rate (ESR)
Time Frame: up to 3 months
up to 3 months
Change in C-reactive protein (CRP)
Time Frame: up to 3 months
up to 3 months
Change in Quality of Life
Time Frame: baseline, 3 months
assessed by the SF-36 questionnaire
baseline, 3 months
Change in Disease Activity Score (DAS 28)
Time Frame: baseline, up to 3 months
Disease Activity Score in 28-joint count
baseline, up to 3 months
Change in duration of morning stiffness
Time Frame: up to 3 months
up to 3 months
Consumption of rescue medication
Time Frame: up to 3 months
up to 3 months
Number of withdrawals due to adverse events
Time Frame: up to 3 months
up to 3 months
Final global assessment of tolerability by investigator on a 4-point scale
Time Frame: 3 months
3 months
Patient's assessment of fatigue by VAS
Time Frame: up to 3 months
up to 3 months
Number of patients with clinically significant changes in laboratory findings
Time Frame: up to 3 months
up to 3 months
Number of patients with clinically significant changes in vital signs
Time Frame: up to 3 months
up to 3 months
Number of patients with clinically significant changes in 12-lead ECG
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2001

Primary Completion (Actual)

November 1, 2002

Study Registration Dates

First Submitted

September 25, 2014

First Submitted That Met QC Criteria

September 25, 2014

First Posted (Estimate)

September 29, 2014

Study Record Updates

Last Update Posted (Estimate)

September 29, 2014

Last Update Submitted That Met QC Criteria

September 25, 2014

Last Verified

September 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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