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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Other: Placebo; Biological: AMP-110

• Registration Number: NCT02277574
• Lead Sponsor: MedImmune LLC

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2014-07-23
• Study First Submitted QC: 2014-10-27
• Study First Posted: 2014-10-29
• Primary Completion: 2015-01
• Study Completion: 2015-07
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-17
• Last Update Posted: 2016-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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:

  1. Rituximab within 6 months
  2. Abatacept within 3 months
  3. Infliximab, Adalimumab, Certolizumab, Tocilizumab, Cyclosporine, Azathioprine or Mycophenolate mofetil within 2 months
  4. Etanercept, Anakinra, immunoglobulin or blood products within 28 days
  5. 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
  6. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Crossover Group 2	Placebo	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
Crossover Group 1	AMP-110	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Optimal dose for repeat dosing of AMP-110	From start of study drug administration through Day 112	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

Trial Locations

Locations (7)

Physician Research Collaboration, LLC; 🇺🇸 Lincoln, Nebraska, United States

Metroplex Clinical Research Center; 🇺🇸 Dallas, Texas, United States

Pinnacle Research Group, LLC; 🇺🇸 Anniston, Alabama, United States

Omega Research Consultants, LLC.; 🇺🇸 Orlando, Florida, United States

Arthritis Center, Inc.; 🇺🇸 Palm Harbor, Florida, United States

Arthritis Treatment Center; 🇺🇸 Frederick, Maryland, United States

Altoona Center for Clinical Research; 🇺🇸 Duncansville, Pennsylvania, United States