A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous AMG 108 in Subjects with Rheumatoid Arthritis. - AMG 108

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-003558-83-IT
• Date of registration: 23/06/2006
• Prospective Registration: No
• Primary sponsor: AMGEN S.P.A.
• Public title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous AMG 108 in Subjects with Rheumatoid Arthritis. - AMG 108
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous AMG 108 in Subjects with Rheumatoid Arthritis. - AMG 108
• Date of first enrolment: 28/04/2006
• Target sample size: 784
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-003558-83
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Austria, Czech Republic, Estonia, Ireland, Italy, Latvia, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must be diagnosed with RA as determined by meeting 1987 American College of Rheumatology ACR classification criteria Appendix H Active RA defined as 8805;6 swollen joints and 8805;6 tender/painful joints and at least one of the following Erythrocyte sedimentation rate ESR 8805;28 mm/hr, C-reactive protein CRP 2.0 mg/dL, or duration of morning stiffness 8805;45 minutes at time of screening Duration of RA for at least 6 months Men or women 8805;18 and 8804;70 years old Subjects with active disease after a minimum of 4 weeks of MTX or 2 weeks of sulfasalazine or hydroxychloroquine treatment. Stable use of oral or SC MTX at 10-25 mg weekly 8805;4 weeks prior to screening If using non-steroidal anti-inflammatory drugs NSAIDs or oral corticosteroids, subjects must be on stable use of NSAIDs or oral corticosteroids 8804;10 mg prednisone or equivalent 8805;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:
Previous receipt of commercial or experimental biologic therapies including AMG 108, anakinra AMG 719, soluble IL-1 type II Page 6 of 123 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 Malignancy within 5 years except 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 Appendix I or radiographic end stage disease 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 Sj gren s syndrome Known to be positive for hepatitis B surface antigen HbsAg , hepatitis C virus HCV or HIV White blood cell count 3.0 x10 3 / L, absolute neutrophil count ANC of 2.5 x 10 3 / L, or platelet count of 125 x 10 3 / L at screening Elevated aspartate aminotransferase AST or alanine aminotransferase ALT 1.5 x upper limit of normal ULN at screening Elevated serum creatinine 1.5 x upper limit of normal or 2 mg/dL 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 6.1 Level: PT Classification code 10039073

Intervention(s)

Product Code: AMG 108
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG 108
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Code: AMG 108
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG 108
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Product Code: AMG 108
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG 108
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the ACR20 response at Week 16.

Secondary Objective: To determine whether AMG 108 at a monthly dose of 250 mg SC or less in combination with MTX demonstrates 20 or higher frequency in clinical response ACR20 above that observed with MTX alone at Week 16. To evaluate the short term safety profile of AMG 108 in combination with MTX in RA subjects at doses up to 250 mg SC per month. To determine whether the clinical response in subjects treated with AMG 108 at one or more doses with concomitant MTX, comparing Week 16 with baseline, is superior to that of MTX alone based on the proportion of subjects achieving an ACR50 and ACR70 response Disease Activity Score DAS 28 and change in DAS28 score from baseline EULAR28 response ACRn measure and AUC ACRn To determine AMG 108 pharmacokinetic parameters in RA subjects after SC administration.

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 16 of therapy.

Secondary ID(s)

AMG 108 20050168

2005-003558-83-GB