Safety and Tolerability of MORAb-022 in Healthy and Rheumatoid Arthritis Subjects

A Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Dose-Escalation Trial of MORAb-022 in Healthy Subjects and Subjects With Rheumatoid Arthritis

This is a randomized, double-blind, placebo-controlled, single-dose, dose escalation study in healthy male and or female subjects and subjects with Rheumatoid Arthritis (RA) to determine the safety and tolerability of MORAb-022.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: MORAb-022

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands
    • Pharmaceutical Research Associates Group B.V.
• United States
  • California
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Seaview Jacksonville, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research

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 for Rheumatoid Arthritis (RA) Subjects:

• Male or female subjects age greater than or equal to 18 years and less than or equal to 75 years.
• Subjects with RA diagnosis per the 2010 Rheumatoid Arthritis Classification Criteria per American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR.)
• BMI less than or equal to 35 kg/m2 at Screening.
• Active RA characterized by DAS28 score of less than or equal to 5.1 at Screening.
• Have been stabilized on their current dose (up to 25 mg/week) of methotrexate(MTX) for at least 4 weeks before randomization.

Exclusion Criteria for Rheumatoid Arthritis (RA)Subjects:

• Subjects with severe active RA and are not on a stable therapeutic regimen at Screening.
• Subjects without significant articular RA.
• Relevant history of significant respiratory disease (e.g., chronic bronchitis, asthma in last 5 years, chronic obstructive pulmonary disease, tuberculosis, interstitial lung disease, such as pneumonitis and pulmonary alveolar proteinosis, as well as significant inhalation exposure to silicon and other substances) that required treatment and/or follow up under the direction of a physician.
• Presence of GM-CSF autoantibodies above normal at Screening.
• Abnormal chest x-ray or PFTs as judged by the investigator at Screening as clinically significant.
• Positive Quantiferon test.
• History of clinically relevant hypersensitivity reactions (e.g., to gold therapy)
• History of medication use that might have carryover effects during the study.
• Previous administration of a GM-CSF modulator within 6 months of randomization, or previous administration of a monoclonal antibody or immunoglobulin fusion protein that is not (or worded as "other than") a GM-CSF modulator within 3 months of randomization.
• Use of any biological therapy other than the test article during the study (informed consent to termination visit)
• Subjects who consume greater than 14 alcoholic drinks per week for males or 7 alcoholic drinks per week for females.
• Weight greater than 120 kg at Screening.
• Use of parenteral and/or intra-articular steroids, immunosuppressants, investigational drugs, and oral anticoagulant drugs within 4 weeks prior to randomization. Oral steroid treatment is permitted if the dosage is less than or equal to 10 mg of prednisone daily, is stable for a minimum of 4 weeks before the study and remains unchanged throughout the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escalating doses of MORAb-022; Subjects with RA will be randomized into Cohorts 8 to 11, with each cohort consisting of five RA subjects per cohort (four active and one placebo).	Drug: MORAb-022; IV infusion of MORAb-022 at increasing doses starting with the minimal anticipated biological effect level (MABEL) which is 0.0085mg/kg.; IV infusion of Placebo (saline)
Placebo Comparator: Placebo; Subjects with RA will be also randomized into Cohorts 8 to 11, with each cohort consisting of five RA subjects per cohort (four active and one placebo).	Drug: MORAb-022; IV infusion of MORAb-022 at increasing doses starting with the minimal anticipated biological effect level (MABEL) which is 0.0085mg/kg.; IV infusion of Placebo (saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety to measures to include adverse events, clinical laboratory results, vital signs, ECGs, physical examinations, local tolerability at the infusion site single escalating intravenous (IV) doses of MORAb-022 in healthy subjects and subjects with RA.	Approximately 113 days

Collaborators and Investigators

• Sponsor: Morphotek
• Investigators: Principal Investigator: Lydie Hazan, MD, Axis Clinical Trials; Principal Investigator: Alan J. Kivitz, MD, CPI, Altoona Center for Clinical Research; Principal Investigator: Chrysoula Pappa, MD, Seaview Jacksonville, LLC; Principal Investigator: William M Schnitz, MD, Lynn Health Science Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: May 18, 2011
• First Submitted That Met QC Criteria: May 19, 2011
• First Posted (Estimate): May 23, 2011

Study Record Updates

• Last Update Posted (Estimate): November 16, 2015
• Last Update Submitted That Met QC Criteria: November 13, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Gimsilumab
• Other Study ID Numbers: MORAB022-001