Rheumatoid Arthritis
Conditions
Keywords
Arthritis, Rheumatoid Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Connective Tissue Diseases, Autoimmune Diseases, Immune System Diseases, Antirheumatic agents
Brief summary
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.
Interventions
BIOLOGICALAMP-110
Dose levels 1 through 7: Single intravenous infusion on Day 0
OTHERPlacebo
Dose levels 4 through 7: Single intravenous infusion on Day 0
Sponsors
Daiichi Sankyo Co., Ltd.
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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: 1. Methotrexate (MTX) 7.5 - 25 mg/week 2. Hydroxychloroquine (HCQ) \</= 400 mg/day 3. Sulfasalazine (SSZ) 1,000 - 3,000 mg/day 4. Leflunomide 5 - 20 mg/day 5. Azathioprine 150 mg/day or 2 mg/kg/day 6. Combinations of MTX, HCQ, and/or SSZ allowed
Exclusion criteria
* Prior to Day 0, use of 1. Abatacept 2. Rituximab within 6 months 3. Infliximab, Adalimumab, Certolizumab, Tocilizumab, Cyclosporine, or Mycophenolate mofetil within 2 months 4. Etanercept or Anakinra within 28 days 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the safety and tolerability of a single dose of AMP-110 versus placebo | From start of study drug administration through Day 56 | 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) |
| Determine Maximum Tolerated Dose and/or recommended dose level(s) for future clinical trials | From start of study drug administration through Day 56 | Based on the occurrence of dose-limiting toxicities (through Day 14) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate pharmacokinetic profile of a single dose of AMP-110 | From Day 0 pre-dose through Day 28 | Pharmacokinetics evaluated by area under the serum concentration versus time curve (AUC), peak serum concentration (Cmax), and clearance (Cl) of AMP-110 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assess pharmacokinetic and pharmacodynamic relationships | From Day 0 pre-dose through Day 56 | Determine if pharmacodynamics effects of AMP-110 on certain cytokine levels and T cell subsets are dependent on serum drug concentrations |
| Evaluate exploratory biomarkers | From start of study drug administration through Day 56 | Blood samples will be analyzed throughout the study to characterize the physiological effects of AMP-110 treatment and to determine markers that correlate with response to treatment |
Countries
United States
Outcome results
None listed