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

A Randomized, Multi-Dose, Placebo-Controlled, Study of the Safety, Tolerability, Pharmacokinetics and Clinical Activity of AMP-110 in Subjects With Rheumatoid Arthritis

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Placebo; Biological: AMP-110

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
  • Florida
    • Orlando, Florida, United States, 32804
      • Omega Research Consultants, LLC.
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center, Inc.
  • Maryland
    • Frederick, Maryland, United States, 21702
      • Arthritis Treatment Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
  • Texas
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crossover Group 1; 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; 2, 5, or 10 mg/kg
Experimental: Crossover Group 2; 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; Placebo

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical responses via RA disease scoring systems	Explore the pharmacodynamics (PD) of repeat doses of AMP-110 versus placebo in subjects with RA	From start of study drug administration through Day 112

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: Daiichi Sankyo Co., Ltd.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: July 23, 2014
• First Submitted That Met QC Criteria: October 27, 2014
• First Posted (Estimate): October 29, 2014

Study Record Updates

• Last Update Posted (Estimate): November 21, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Arthritis; Rheumatoid arthritis; Musculoskeletal diseases; Joint diseases
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: AMP-110-02