Rheumatoid arthritis (RA)
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Major inclusion criteria are: • Subjects must be diagnosed with RA as determined by meeting 1987 American College of Rheumatology ( ACR) classification criteria. • Active RA defined as = 6 swollen joints and = 6 tender/painful joints and at least one of the following: Erythrocyte sedimentation rate (ESR) = 28 mm/hr, C-reactive protein (CRP) > 2.0 mg/dL, or duration of morning stiffness = 45 minutes at time of screening • Duration of RA for at least 6 months • Men or women =18 and = 70 years old • Subjects must be taking MTX consecutively for =12 weeks and on a stable dose of oral or SC MTX at 15-25 mg weekly for =4 weeks at screening. A lower MTX dose is acceptable if it is the highest tolerated dose (toxicity documentation required) • If using non-steroidal anti-inflammatory drugs (NSAIDs) or oral corticosteroids, subjects must be on stable use of NSAIDs or oral corticosteroids (=10 mg prednisone or equivalent) =4 weeks prior to screening • Before any study-specific procedure, the appropriate written informed consent must be obtained Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Major exclusion criteria are: • Previous receipt of commercial or experimental biologic therapies including AMG 108, anakinra (Kineret®), AMG 719, soluble IL-1 type II receptor, etanercept, infliximab, adalimumab, onercept, pegsunercept, abatacept, or rituximab or any other biologic therapy used to treat an inflammatory disease • Uncontrolled, clinically significant systemic disease other than RA such as diabetes mellitus, cardiovascular disease or hypertension • Uncontrolled or clinically significant asthma • Malignancy within 5 years (except successfully treated in-situ cervical cancer or squamous or basal cell carcinoma) • Presence of a serious infection, defined as requiring hospitalization or recurrent, acute or chronic infections within 8 weeks before screening • Prior or current history of Mycobacterium tuberculosis infection or exposure • Class IV RA (Hochberg 1992) according to ACR revised response criteria • Prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening • Felty’s syndrome • Major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren’s syndrome • Known to be positive for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) or HIV • Uncontrolled, clinically significant history of hematologic abnormality or white blood cell count 1.5 x upper limit of normal (ULN) at screening • Uncontrolled, clinically significant history of renal disease or elevated serum creatinine > 1.5 x upper limit of normal at screening • Laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results • Intra-articular (IA) or systemic corticosteroid injections within 4 weeks of screening • Any DMARD other than MTX within 6 weeks of screening • Cyclophosphamide within 6 months of screening • Received live vaccines within 3 months of first dose of investigational product • Any investigational therapy within 4 weeks of screening • Pregnant or nursing • Sexually active subjects and their partners who are of childbearing potential (ie, neither surgically sterile nor postmenopausal) and not using adequate contraception • Known sensitivity to mammalian cell derived drug products • Any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results • Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures • Active substance abuse (within 24 weeks of screening) • Requiring or having a condition that may be expected to require strong narcotic analgesics (except hydrocodone, codeine, dextropropoxyphene, propoxyphene, or oxycodone) or morphine derived medication for analgesic relief at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective for this study is to determine whether AMG 108, at a monthly dose of 250 mg subcutaneous (SC) or less, in combination with methotrexate (MTX) demonstrates a higher frequency in clinical response (ACR20) than that observed with placebo (MTX alone) in RA subjects at Week 24 of therapy. ;Secondary Objective: To determine: AMG 108, at monthly dose of 250 mg SC or less, in combination with methotrexate (MTX) demonstrates 20% or higher frequency in clinical response (ACR20) above that observed with MTX alone at Week 24 Any improvement over MTX alone from baseline in subject reported outcomes measure Health Assessment Questionnaire - Disability Index (HAQ- DI) at Week 24 The clinical response in subjects treated with AMG 108 at one or more doses with concomitant MTX, comparing Week 24 with baseline, is superior to that of MTX alone based on: 1 Proportion of subjects achieving an ACR50 & ACR70 response 2 DAS28 score and change in DAS28 score from baseline (EULAR28 response) 3 ACRn measure and AUC ACRn AMG 108 pharmacokinetic parameters in RA subjects after SC administration Any improvement over MTX alone from baseline in subject reported outcomes measure SF- 36 at Week 24 The short term safety profile of AMG 108 in combination with MTX in RA subjects at doses up to 250 mg SC per month;Primary end point(s): The primary endpoint is the ACR20 response at Week 24. The secondary endpoints are:· • Change in subject reported outcomes measure HAQ-DI at Week 24 • ACR50 and ACR70 responses at Week 24· • Change in DAS28 score from baseline (EULAR28 response) at Week 24· • Change in subject reported outcomes measure SF-36 at Week 24 • ACRn and AUC ACRn at Week 24· • AMG 108 PK parameters (such as Cmax, Tmax, and AUC0-t) after the 1st dose (on Day 1) and after the 6th dose for the intensive sampling group. The safety endpoints include:· • Treatment-emergent adverse events and infectious adverse events· • Serious adverse events (SAEs) and se | — |
Countries
Austria, Czech Republic, Estonia, Ireland, Italy, Latvia, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed