Study to Evaluate the Safety, Tolerability, and Action of AMG 357 in Females With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of the study is to find out if AMG 357 is safe and tolerated by women with Rhematoid Arthritis.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Ascending Multiple-dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 357 in Female Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: AMG 357
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject provided informed consent. Rheumatoid arthritis present for ≥ 3 months. Global functional class I, II, or III. History of or positive for, Rheumatoid Arthritis Taking methotrexate consecutively for ≥ 12 weeks and on a stable dose at 10-25 mg weekly. Subjects currently taking NSAIDs or oral corticosteroids. Normal ECG values Immunizations up to date. Exclusion Criteria: Positive Hepatitis B, Hepatitis C, Positive HIV Sensitivity to any of the products or components to be administered. Malignancy within 3 years Presence of recurrent or chronic infections Evidence of infections within the 30 days prior to randomization Presence of a serious infection Prosthetic joint infection within 3 years or native joint infection within 1 year History of exposure to tuberculosis without a history of prophylactic treatment Class IV RA. Felty's syndrome Chronic pelvic pain or hemorrhagic ovarian cyst within 3 years Any bleeding disorder that is clinically significant Low white blood cell or neutrophil count Elevated serum creatinine clearance Low hemoglobin and platelet count Received live vaccines within 3 months of first dose Alcohol and/or substance abuse within past 12 months Blood donation within 60 days Positive urine screen for drugs of abuse Any prior use of rituximab in the last 6 months (or other B cell depleting agents) and CD19 levels < lower limits of normal Use of a weekly or bimonthly biologic within 2 weeks or monthly biologic agents within 4 weeks Corticosteroid injections for acute RA flare within 4 weeks Grapefruit juice or grapefruit containing products within 7 days of first dose. All herbal medicines, vitamins, and supplements within the 30 days The use of any experimental/investigational biologic DMARD unless off agent for 3 months; or off for 6 months for B cell depleting agents Known GI disease or GI procedures Women of reproductive potential who are unwilling to practice birth control Women who are pregnant/lactating/breastfeeding Subject with IgG levels < lower limit of normal at screening

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 357<br> | Drug: AMG 357<br>* Oral tablets in 20 count bottles. Dose strengths include 5, 25, and 50 mg tablets.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral tablets in 20 count bottles. Dose strengths include 5, 25, and 50 mg tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects reporting of treatment-emergent adverse events or clinically significant changes in physical examinations, vital signs, laboratory safety tests, and ECGs |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AMG 357 pharmacokinetic profile (eg, plasma concentration, maximum observed concentration [Cmax], time at Cmax [Tmax], and area under the concentration-time curve [AUC]) |  | 1 year |