Study to Assess the Safety, Tolerability, and Pharmacokinetics of AMP-110 in Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This is a Phase 1, single-dose, placebo-controlled, dose-escalation,multi-center, first time in human study of AMP-110 in adult subjects with rheumatoid arthritis.

Official Title
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A Randomized, Single-Dose, Placebo-Controlled, Study of the Safety, Tolerability, and Pharmacokinetics of AMP-110 in Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: AMP-110
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to provide written informed consent Body mass index 18.5 to 35.0 kg/m2 Diagnosis of Rheumatoid Arthritis according to 1987 revised American College of Rheumatology (ACR) criteria Global Functional Class I, II, or III according to ACR 1991 revised criteria Stable use of >/= 1 Disease Modifying Anti-rheumatic Drugs (DMARD) for >/= 4 weeks prior to Day 0, including: Methotrexate (MTX) 7.5 - 25 mg/week Hydroxychloroquine (HCQ) </= 400 mg/day Sulfasalazine (SSZ) 1,000 - 3,000 mg/day Leflunomide 5 - 20 mg/day Azathioprine 150 mg/day or 2 mg/kg/day Combinations of MTX, HCQ, and/or SSZ allowed Exclusion Criteria: Prior to Day 0, use of Abatacept Rituximab within 6 months Infliximab, Adalimumab, Certolizumab, Tocilizumab, Cyclosporine, or Mycophenolate mofetil within 2 months Etanercept or Anakinra within 28 days Immunoglobulin or blood products within 28 days Evidence of any active or recent infection including ongoing, chronic infectious disease such as chronic renal infection or chronic chest infection with bronchiectasis or sinusitis History of systemic autoimmune disease other than Rheumatoid Arthritis History of allergic reactions to other protein therapeutics such as monoclonal antibodies or fusion proteins History of anaphylaxis or allergic diathesis Clinically significant cardiac disease, including: unstable angina; myocardial infarction within 6 months; congestive heart failure; arrhythmia requiring active therapy, with the exception of clinically insignificant extrasystoles, or minor conduction abnormalities; and history of clinically significant abnormality on electrocardiogram Evidence of active or latent tuberculosis Vaccination wtih live attenuated viruses within the 2 weeks prior to Day 0 Evidence of infection with hepatitis B virus, hepatitis C virus, human immunodeficiency virus 1 or 2, or active infection with hepatitis A Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMP-110<br>Escalating doses of AMP-110 | Biological: AMP-110<br>* Dose levels 1 through 7: Single intravenous infusion on Day 0<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Dose levels 4 through 7: Single intravenous infusion on Day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety and tolerability of a single dose of AMP-110 versus placebo | Evaluate number of subjects with dose-limiting toxicities (through Day 14), evaluate number of subjects wtih adverse events (through Day 56), and number of subjects wtih changes from baseline in laboratory values, vital signs, physical exam and electrocardiogram (through Day 56) | From start of study drug administration through Day 56 | 
| Determine Maximum Tolerated Dose and/or recommended dose level(s) for future clinical trials | Based on the occurrence of dose-limiting toxicities (through Day 14) | From start of study drug administration through Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate pharmacokinetic profile of a single dose of AMP-110 | Pharmacokinetics evaluated by area under the serum concentration versus time curve (AUC), peak serum concentration (Cmax), and clearance (Cl) of AMP-110 | From Day 0 pre-dose through Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Connective Tissue Diseases, Autoimmune Diseases, Immune System Diseases, Antirheumatic agents, Arthritis