- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02214888
Efficacy, Safety and Pharmacokinetics of BIRB 796 BS Tablets in Patients With Active Rheumatoid Arthritis
A 12 Week Double-blind, Randomized, Placebo-controlled Trial to Investigate Efficacy, Safety and Pharmacokinetics of BIRB 796 BS Tablets at Doses of 50 and 70 mg Administered Twice a Day in Patients With Active Rheumatoid Arthritis Who Have Failed at Least One DMARD
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female from 18 to 75 years of age
- Diagnosis of rheumatoid arthritis (RA) established according to ACR criteria and date of diagnosis > 6 months
- Patient belonging to functional class I, II, or III
- Failure of at least one DMARD due to lack of efficacy or tolerability
2 out of the 3 following RA activity criteria: If this criterion is not met at visit 1, the whole set of RA activity criteria can be repeated at visit 2 (Repeated screening)
- documentation of ≥ 9 swollen joints in a 66 joint count
- documentation of ≥ 9 tender joints in a 68 joint count
- C-reactive protein (CRP) ≥ 1.5 mg/dl or erythrocyte sedimentation rate (ESR) ≥ 28 mm/hr (or equivalent of ≥ 24mm/hr according to Panchenkov method)
- Written informed consent in accordance with Good Clinical Practice (GCP) and local legislation given prior to any study procedures, including washout of prohibited medications
- Only for centres participating in the pharmacokinetic (PK) substudy: Written informed consent in accordance with GCP and local legislation for participation in the PK substudy. Refusal to participate in the PK substudy is not an exclusion criterion for participation in the trial
Exclusion Criteria:
- Inflammatory rheumatic disease other than RA
- Treatment failure to a tumor necrosis factor (TNF)-blocking agent. Treatment failure is defined as not achieving at least an ACR 20 response (e.g. in a clinical trial) or - in clinical practice - having the TNF-blocking agent discontinued due to ineffectiveness
- History of vasculitis (characterised by e.g. nail bed hemorrhages or infarcts, vasculitic purpura, ulcers or gangrene, multisensory neuropathy, vasculitic retinopathy or scleritis of eyes). Isolated rheumatoid nodules of the skin are not a criterion for exclusion
- Serologic evidence of active hepatitis B and/or C
- Known HIV-infection
- History of prior tuberculosis infection or suspicion of active infection at screening based on results of chest x-ray not older than 6 months
- History of cardiovascular, renal, neurologic, psychiatric, liver, gastrointestinal, immunologic or endocrine dysfunction if they are clinically significant. A clinically significant disease is defined as one which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
- Recent history of heart failure (i.e. three years or less) or myocardial infarction (i.e. one year or less) or patients with any cardiac arrhythmia requiring drug therapy
- History of malignant disease in the last 5 years or suspicion of active malignant disease except successfully treated squamous or basal cell carcinoma of the skin
- Screening ECG results outside of the reference range of clinical relevance including, but not limited to QTcB > 480 msec, PR interval > 240 msec, QRS interval > 110 msec according to central ECG evaluation
Clinically significant abnormal baseline hematology, blood chemistry or urinalysis if the abnormality defines a disease listed as an exclusion criterion or any of the following specific laboratory abnormalities: If this criterion is not met at visit 1, the laboratory assessments can be selectively repeated at visit 2 (Repeated screening)
- alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin greater than upper limit of normal (ULN)
- alkaline phosphatase, creatinine or white blood cell count greater than 1.5 x ULN
- History of drug or alcohol abuse within the past two years or active drug or alcohol abuse, present alcohol intake more than three drinks per day
- Female of childbearing potential (not 6 months post- menopausal or surgically sterilized) not using an approved form of birth control (hormonal contraceptives, oral or injectable/implantable, intra-uterine device (IUD))
- Inability to comply with the protocol
- Previous enrolment in this trial or previous exposure to BIRB 796 BS in another trial
- Hypersensitivity to trial drug
To be assessed at visit 3 (Baseline):
- Pregnancy (to be excluded by serum and urine beta human chorion-gonadotropin (βHCG)-test in women of childbearing potential) or breast feeding
- Active vasculitis
- Active infection or serious infectious diseases resulting in hospitalisation or requiring systemic anti-infective therapy within the last 4 weeks
- DMARD treatment within the last 4 weeks
Last dose given within the specified time period for one of the following compounds or drugs:
- Infliximab (Remicade®): 3 months
- Adalimumab (D2E7): 3 months
- Leflunomide: 3 months. If cholestyramine has been given for 10 days : 4 weeks
- Investigational agent: 5- fold of the respective plasma half life or 4 weeks, whichever is longer
- Treatment with systemic corticosteroids in a dose higher than 10 mg/day prednisone equivalent
- Change in treatment with nonsteroidal antiinflammatory drugs (NSAIDs) or systemic corticosteroids within the last 4 weeks
- Synovectomy, joint surgery, radio-/chemo synoviorthesis, adrenocorticotropic hormone (ACTH) or any steroid injections (intraarticular, intravenous or intramuscular) within the last 4 weeks
- Participation in another clinical trial within the last 4 weeks
Study Plan
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: BIRB 796 BS, low dose
|
|
Experimental: BIRB 796 BS, high dose
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of responders according to the American College of Rheumatology (ACR) 20 criteria
Time Frame: after 12 weeks of treatment
|
after 12 weeks of treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Absolute differences to baseline in tender joint count (TJC, 68 joint count)
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Absolute differences to baseline swollen joint count (SJC, 66 joint count)
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Absolute differences to baseline in patients assessment of pain on a visual analogue scale (VAS)
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Absolute differences to baseline in patients global assessment of disease activity (PADA) on a VAS
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Absolute differences to baseline in physicians global assessment of disease activity on a VAS
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Absolute differences to baseline in patient's assessment of physical function measured by a standardised Health Assessment Questionnaire (HAQ)
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Absolute differences to baseline in concentration of C-reactive protein (CRP)
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Absolute differences to baseline in erythrocyte sedimentation rate (ESR)
Time Frame: up to 12 weeks
|
up to 12 weeks
|
Number of responders to ACR 50
Time Frame: after 12 weeks of treatment
|
after 12 weeks of treatment
|
Number of responders to ACR 70
Time Frame: after 12 weeks of treatment
|
after 12 weeks of treatment
|
Number of responders to European League against Rheumatism (EULAR) response criteria
Time Frame: after 12 weeks of treatment
|
after 12 weeks of treatment
|
Number of drop-outs due to lack of efficacy, according to final assessment of investigator
Time Frame: after 12 weeks of treatment
|
after 12 weeks of treatment
|
Number of patients with adverse Events (AE)
Time Frame: up to 12 weeks after first drug administration
|
up to 12 weeks after first drug administration
|
Number of patients with clinically relevant changes in laboratory tests
Time Frame: up to 12 weeks after first drug administration
|
up to 12 weeks after first drug administration
|
Number of patients with clinically relevant changes in electrocardiogram (ECG)
Time Frame: up to 12 weeks after first drug administration
|
up to 12 weeks after first drug administration
|
Number of patients with clinically relevant changes in vital signs
Time Frame: up to 12 weeks after first drug administration
|
up to 12 weeks after first drug administration
|
Number of withdrawals due to AEs
Time Frame: up to 12 weeks after first drug administration
|
up to 12 weeks after first drug administration
|
Cmax,ss (Maximum measured concentration of the analyte in plasma at steady state)
Time Frame: up to 24 hours after last drug administration
|
up to 24 hours after last drug administration
|
AUC0-t,ss (area under the drug plasma concentration-time curve over a dosing interval (t) at steady state
Time Frame: up to 24 hours after last drug administration
|
up to 24 hours after last drug administration
|
Cpre (predose concentration of the analyte in Plasma)
Time Frame: up to 24 hours after last drug administration
|
up to 24 hours after last drug administration
|
Cmin,ss (Minimum measured concentration of the analyte in plasma at steady state)
Time Frame: up to 24 hours after last drug administration
|
up to 24 hours after last drug administration
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1175.18
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.
Clinical Trials on Arthritis, Rheumatoid
-
Janssen Research & Development, LLCWithdrawnActive Rheumatoid Arthritis; Rheumatoid Arthritis
-
Centocor, Inc.CompletedRheumatoid Arthritis, Juvenile
-
National Institute of Arthritis and Musculoskeletal...Children's Hospital Medical Center, CincinnatiCompleted
-
University of PittsburghNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedRheumatoid Arthritis | Juvenile Rheumatoid ArthritisUnited States
-
University of Missouri-ColumbiaCompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenTerminated
-
Children's Hospital Medical Center, CincinnatiNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenImmunex CorporationCompletedJuvenile Rheumatoid Arthritis
-
Universidad Autonoma de Nuevo LeonCompletedRheumatoId ArthritisMexico
-
Hamad Medical CorporationUnknownRHEUMATOID ARTHRITISQatar
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States