A Multi-center Study a Single IV Infusion of Allogeneic MPCs in Patients With Rheumatoid Arthritis and Incomplete Response to at Least One TNFα Inhibitor

A Double-blind, Randomized, Placebo-controlled, Dose-escalation, Multi-center Study a Single Intravenous Infusion of Allogeneic Mesenchymal Precursor Cells (MPCs) in Patients With Rheumatoid Arthritis and Incomplete Response to at Least One TNFα Inhibitor

Study is a double-blind, randomized, placebo controlled, dose escalating study. The primary objective of this study is to evaluate the safety, tolerability and feasibility of a single intravenous infusion of allogeneic mesenchymal precursor cells (MPCs) compared to placebo at 12 weeks post-infusion in the treatment of patients with active rheumatoid arthritis (RA) who have received methotrexate +/- other DMARDs for at least 6 months prior to screening and who have had an incomplete response to at least one TNF-alpha inhibitor.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Normal Saline; Drug: Allogeneic Mesenchymal Precursor Cells

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Southern Clinical Research Pty Ltd
  • Victoria
    • Malvern, Victoria, Australia, 3145
      • Emeritus Research
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Arthrocare Arthritis Care and Research PC
  • California
    • El Cajon, California, United States, 92020
      • Triwest Research Associates
    • Los Angeles, California, United States, 90025
      • UCLA
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials Incorporated
  • Florida
    • Ocala, Florida, United States, 34474
      • Ocala Rheumatology Research Center
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
    • Tampa, Florida, United States, 33614
      • McIlwain Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • JHU Arthritis Center Baltimore
    • Frederick, Maryland, United States, 21702
      • Arthritis Treatment Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Reliant Medical Group
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Fair Lawn, New Jersey, United States, 07410
      • Office of Ramesh C. Gupta, MD
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Health Research of Oklahoma
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
  • Texas
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research
    • San Antonio, Texas, United States, 78217
      • Texas Arthritis Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and Females ages 18-80 years old
• Active rheumatoid arthritis (RA) disease as per 2010 ACR/EULAR classification criteria for the diagnosis of RA.
• Must be positive for rheumatoid factor and/or anti-cyclic citrullinated peptide (anti-CCP3) but without extra-articular disease or functional limitation

• Patient with active RA defined as:

  • ≥ 4 tender joint count (TJC) 28 joint count at screening and
  • ≥ 4 swollen joint count (SJC) count 28 joint count at screening
  • ESR ≥ 28 mm/hr or hsCRP >2.0 mg/L
• Patient has been taking MTX for at least 4 months with dose and route of administration stable for at least 8 weeks prior to screening
• Patient has had an inadequate response to at least one TNFα inhibitor with last dose at least 6 weeks prior to screening
• Use of oral DMARD (sulfasalazine, hydroxychloroquine, chloroquine and leflunomide) is permitted but must be stable for at least 3 months prior to screening

Exclusion Criteria:

• Pregnant women or women who are breastfeeding.
• Other investigational therapy received within 8 weeks or five half-lives (whichever is longer) prior to Screening (except as in exclusion #13).
• Known or suspected alcohol or drug abuse within three years preceding Screening.
• Autoimmune disease other than RA (such as systemic lupus erythematosus (SLE), mixed connective tissue disease, scleroderma, polymyositis/dermatomyositis, vasculitis)
• History of or current inflammatory joint disease other than RA (such as tophaceous gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis or other spondyloarthropathy, Lyme disease). Patients primarily diagnosed with osteoarthritis are excluded.
• Bedridden or confined to a wheelchair or patients with > 3 arthroplasties due to RA.
• History of diagnosed and/or treated malignancy with no evidence of recurrence in past 5 years
• Surgical procedures planned to occur during the trial (these patients may be rescreened following completion of and recovery from the surgical procedure).
• Use of TNFα inhibitor for treatment of RA at time of screening or within the 6 weeks prior to screening.
• Prior use of biologic agent for treatment of RA within 6 weeks prior to screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal Saline Placebo; Placebo will be delivered in 100 mL normal saline administered intravenously over approximately 45 minutes.	Drug: Allogeneic Mesenchymal Precursor Cells
Active Comparator: Allogeneic Mesenchymal Precursor Cells; Mesenchymal Precursor Cells (MPCs), either 1.0 or 2.0 million cells/kg, will be delivered in 100 mL normal saline administered intravenously over approximately 45 minutes.	Drug: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the safety of a single IV infusion of allogeneic MPCs compared to placebo at 12 weeks post-infusion	To evaluate the safety, tolerability and feasibility of a single intravenous (IV) infusion of allogeneic mesenchymal precursor cells (MPCs) compared to placebo at 12 weeks post-infusion in the treatment of patients with active rheumatoid arthritis (RA) who have received methotrexate +/- other oral DMARDs for at least 4 months and who have had an incomplete response to at least one course of a TNFα inhibitor. Overall safety will be based on the overall assessment of AE/SAEs, Vital Signs, Physical Examination, clinical laboratory tests, ECGs and Chest x-ray.	12 weeks post IV Infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the efficacy of a single intravenous infusion of allogeneic MPCs compared with placebo at 12 weeks post-infusion with MPCs or placebo in the treatment of patients with active RA	To assess the efficacy of a single intravenous infusion of allogeneic MPCs compared with placebo at 12 weeks post-infusion with MPCs or placebo in the treatment of patients with active RA who have received methotrexate +/- other DMARDs for at least 4 months and who have had an incomplete response to least one TNFα inhibitor.	12 weeks post IV infusion with MPCs
Evaluation of long-term safety and efficacy of a singly IV infusion of allogeneic MPCs in patients with active RA	To evaluate the long-term efficacy and safety of allogeneic MPCs over the entire study duration in the treatment of patients with active RA who have received methotrexate +/- other DMARDs for at least 4 months and who have had an incomplete response to at least one TNFα inhibitor Safety will be assessed according to the following: Adverse events/serious adverse events ("primary endpoint"); Vital signs; Physical examination; Clinical laboratory tests; Electrocardiogram; Chest x-ray (CXR) Efficacy will be assessed according to the following: ACR20/50/70; DAS28 (mean changes from baseline as measured by using hsCRP and ESR); Mean changes from baseline in all components of the ACR core response criteria; Remissions (as defined in the 2011 Joint Statement of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR); Joint erosion of hands and wrists assessed via x-ray; Patient-reported outcomesSF36v2HAQ_DI	52 weeks post IV Infusion

Collaborators and Investigators

• Sponsor: Mesoblast, Ltd.
• Collaborators: PPD

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: April 19, 2013
• First Submitted That Met QC Criteria: May 9, 2013
• First Posted (Estimate): May 10, 2013

Study Record Updates

• Last Update Posted (Actual): June 26, 2020
• Last Update Submitted That Met QC Criteria: June 25, 2020
• Last Verified: June 1, 2020

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
• Other Study ID Numbers: MSB-RA001