Safety and Efficacy of AMG 827 in Subjects With RA

Amgen

Status and phase: Terminated; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: AMG 827

Study type: Interventional

Funder types: Industry

Identifiers

NCT01059448

20090402

Details and patient eligibility

About

This is an extension study for subjects who participated in Protocol 20090061 (NCT00950989). All subjects in this study will receive a 210mg injection of AMG827 for treatment for their Rheumatoid Arthritis for up to 5 years.

Enrollment: 211 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subject has provided informed consent.
• Subject was randomized into study 20090061 and completed the week 16 evaluation.
• Negative test for hepatitis B virus (HBV) surface antigen, hepatitis C virus (HCV) antibody, and/or human immunodeficiency virus (HIV) in subjects if clinically indicated (eg, known recent exposure) in the opinion of the investigator.
• Subject must test negative for Tuberculosis.

Exclusion criteria

• Subject had any SAE reported during 20090061 that was considered to be related to IP.
• Subject is currently experiencing an infection of CTCAE grade 2 (if requiring oral antibiotics) or higher. Subject is ineligible until the infection is resolved in the opinion of the investigator.
• For subjects with > 4 weeks between the week 16 visit of 20090061 and the planned first IP dose in 20090402, subject has laboratory abnormalities at screening, including:
• Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT); >1.5x upper limit of normal)
• Serum total bilirubin ≥1.5 mg/dL
• Hemoglobin < 11 g/dL
• Platelet count < 125,000 /mm3
• White blood cell count < 3,000 cells/mm3
• Absolute neutrophil count < 2000/mm3
• Estimated creatinine clearance < 50 mL/min (Cockroft-Gault formula, central lab will calculate value and provide to sites)
• Subject has a significant concurrent medical conditions, including:
• Type 1 diabetes
• Poorly controlled type 2 diabetes (Hemoglobin A1c > 8.5)
• Symptomatic heart failure (New York Heart Association class II, III, or IV)
• Myocardial infarction within the last year
• Current or history of unstable angina pectoris within the last year
• Uncontrolled hypertension as defined by resting blood pressure > 150/90 mmHg prior to first IP dose (confirmed by a repeat assessment)
• Severe chronic pulmonary disease (eg, requiring oxygen therapy)
• Major chronic inflammatory disease or connective tissue disease other than rheumatoid arthritis (eg, systemic lupus erythematosus), with the exception of secondary Sjögren's syndrome
• Multiple sclerosis or any other demyelinating disease
• Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin)
• Any condition that, in the opinion of the investigator, might cause this study to be detrimental to the subject
• Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the subject's last study visit including the follow-up period.
• Female subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study and at least 40 days after the last dose (except women at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control for women include but are not limited to birth control pills, Depo Provera® injections, contraceptive implants, or occlusive cap (barrier method) in combination with barrier methods used by the man.
• Male subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study, plus an additional 16 weeks after the last dose (except for men who are surgically sterile or whose female partners are at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control include but are not limited to a condom in combination with hormonal birth control or barrier methods used by the woman.
• Male subject (including vasectomised males) with a pregnant female partner is not willing to use effective methods to ensure that an unborn child is not exposed to AMG 827 via semen. Effective methods to ensure that an unborn child is not exposed to AMG 827 via semen include condoms or abstinence.
• Subject has used any of the following within 14 days prior to IP initiation
• Non-biologic disease-modifying anti-rheumatic drugs (DMARD) other than as allowed in 20090061
• Intra-articular, intramuscular, or intravenous corticosteroids, including adrenocorticotropic hormone
• Subject has used any of the following within 3 months prior to IP initiation
• Leflunomide
• Live vaccines
• Commercially available or experimental biologic DMARD except for AMG 827
• Subject has received gold therapy within 6 months prior to IP initiation.
• Subject received another investigational agent (other than AMG 827) or participated in an investigational device study subsequent to 20090061.
• Other investigational procedures are excluded.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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211 participants in 4 patient groups

Placebo Q2WK / 210 mg AMG 827 Q2WK

Experimental group

Description:

Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Treatment:

Drug: AMG 827

70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK

Experimental group

Description:

Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Treatment:

Drug: AMG 827

140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK

Experimental group

Description:

Participants who were administered 140 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Treatment:

Drug: AMG 827

210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK

Experimental group

Description:

Participants who were administered 210 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Treatment:

Drug: AMG 827