Assess Safety, Tolerability, Pharmacokinetics and Clinical Activity of AMP-110 in Subjects With Rheumatoid Arthritis

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

Official Title
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A Randomized, Multi-Dose, Placebo-Controlled, Study of the Safety, Tolerability, Pharmacokinetics and Clinical Activity 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 Must have at least 4 tender joints and 4 swollen joints (28-joint assesssment) Use of >/= 1 non-steroidal anti-inflammatory drugs is allowed, subject must be on a stable dose for >/= 2 weeks prior to randomization Use of >/= 1 Disease Modifying Anti-rheumatic Drugs (DMARD) for >/= 3 months and a stable dose for >/= 6 weeks prior to randomization Stable use of low dose oral corticosteroids (</= 10 mg prednisone per day or equivalent) is allowed; subjects must be on a stable dose for >/= 4 weeks prior to randomization Exclusion Criteria: Prior to Day 0, use of: Rituximab within 6 months Abatacept within 3 months Infliximab, Adalimumab, Certolizumab, Tocilizumab, Cyclosporine, Azathioprine or Mycophenolate mofetil within 2 months Etanercept, Anakinra, immunoglobulin or blood products within 28 days Prior immunotherapy, including high dose oral corticosteroids or systemic corticosteroids such as prednisone, biologics, Janus kinase (JAK) inhibitors, such as tofacitinib or investigational therapy must have completed at least 5 half-lives or 30 days, whichever is longer Prior exposure to T cell depleting agents such as Campath (alemtuzumab) Evidence of any active or recent infection History of systemic autoimmune disease other than Rheumatoid Arthritis; secondary Sjogren's syndrome, rheumatoid vasculitis and orther extra-articular manifestations of RA allowed History of allergic reactions 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 with live attenuated viruses within the 2 weeks prior to Day 0 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crossover Group 1<br>Subjects assigned to this arm will receive 1 of 3 escalating doses of AMP-110 once a week for 4 weeks followed by 4 weekly doses of placebo | Biological: AMP-110<br>* 2, 5, or 10 mg/kg<br>|
| Experimental: Crossover Group 2<br>Subjects assigned to this arm will receive 4 weekly doses of placebo followed by 1 of 3 escalating doses of AMP-110 once a week for 4 week | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptable number of adverse events per subject as a measure of safety and tolerability of repeat doses of AMP-110 versus placebo | Determined by the number of AEs, SAEs, and results in laboratory evaluations, vital signs, electrocardiograms and physical examinations | From start of study drug administration through Day 112 | 
| Repeat dose pharmacokinetic parameters of AMP-110 in serum | Parameters will include maximum observed concentration (Cmax), area under the concentration-time curve (AUC), total body clearance and terminal half-life | From start of study drug administration through Day 112 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal dose for repeat dosing of AMP-110 | Optimal dose will be determined through the occurrence of AEs, SAEs, ACR-20 and DAS-28 results, and individual AMP-110 concentrations in serum including peak and trough levels | From start of study drug administration through Day 112 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, Arthritis, Joint diseases, Musculoskeletal diseases