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

NCT01851070 | Completed Phase 2 DMC

• 1 other identifier: MSB-RA001
• Study Type: interventional
• Target: 48
• Locations: 2 countries
• Sites: 23

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

  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

  52 weeks post IV Infusion

Study Arms (2)

Normal Saline Placebo

PLACEBO COMPARATOR

Placebo will be delivered in 100 mL normal saline administered intravenously over approximately 45 minutes.

Drug: Allogeneic Mesenchymal Precursor Cells

Allogeneic Mesenchymal Precursor Cells

ACTIVE COMPARATOR

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

Interventions

Allogeneic Mesenchymal Precursor Cells DRUG

Normal Saline Placebo

Normal Saline DRUG

Allogeneic Mesenchymal Precursor Cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnant women or women who are breastfeeding.
• 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

Sponsors & Collaborators

• Mesoblast, Ltd.: lead
• PPD Development, LP: collaborator

Study Sites (23)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Arthrocare Arthritis Care and Research PC

Gilbert, Arizona, 85234, United States

Location

Triwest Research Associates

El Cajon, California, 92020, United States

Location

UCLA

Los Angeles, California, 90025, United States

Location

Inland Rheumatology Clinical Trials Incorporated

Upland, California, 91786, United States

Location

Ocala Rheumatology Research Center

Ocala, Florida, 34474, United States

Location

Arthritis Center

Palm Harbor, Florida, 34684, United States

Location

Sarasota Arthritis Research Center

Sarasota, Florida, 34239, United States

Location

McIlwain Medical Group

Tampa, Florida, 33614, United States

Location

JHU Arthritis Center Baltimore

Baltimore, Maryland, 21224, United States

Location

Arthritis Treatment Center

Frederick, Maryland, 21702, United States

Location

Reliant Medical Group

Worcester, Massachusetts, 01605, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Office of Ramesh C. Gupta, MD

Fair Lawn, New Jersey, 07410, United States

Location

DJL Clinical Research

Charlotte, North Carolina, 28210, United States

Location

Health Research of Oklahoma

Oklahoma City, Oklahoma, 73102, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

West Tennessee Research Institute

Jackson, Tennessee, 38305, United States

Location

Accurate Clinical Research

Houston, Texas, 77034, United States

Location

Texas Arthritis Research Center

San Antonio, Texas, 78217, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Southern Clinical Research Pty Ltd

Hobart, Tasmania, 7000, Australia

Location

Emeritus Research

Malvern, Victoria, 3145, Australia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Donna Skerrett, MD, MS

  Mesoblast, Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2013
• First Posted: May 10, 2013
• Study Start: July 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: March 1, 2017
• Last Updated: June 26, 2020

Record last verified: 2020-06

Locations

US (20); AU (3)