search
Back to results

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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Allogeneic Mesenchymal Precursor Cells
Normal Saline
Sponsored by
Mesoblast, Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pinnacle Research Group
  • Arthrocare Arthritis Care and Research PC
  • Triwest Research Associates
  • UCLA
  • Inland Rheumatology Clinical Trials Incorporated
  • Ocala Rheumatology Research Center
  • Arthritis Center
  • Sarasota Arthritis Research Center
  • McIlwain Medical Group
  • JHU Arthritis Center Baltimore
  • Arthritis Treatment Center
  • Reliant Medical Group
  • Mayo Clinic
  • Office of Ramesh C. Gupta, MD
  • DJL Clinical Research
  • Health Research of Oklahoma
  • University of Pittsburgh
  • West Tennessee Research Institute
  • Accurate Clinical Research
  • Texas Arthritis Research Center
  • Royal Prince Alfred Hospital
  • Southern Clinical Research Pty Ltd
  • Emeritus Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Normal Saline Placebo

Allogeneic Mesenchymal Precursor Cells

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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 outcomes SF36v2 HAQ_DI

Full Information

First Posted
April 19, 2013
Last Updated
June 25, 2020
Sponsor
Mesoblast, Ltd.
Collaborators
PPD
search

1. Study Identification

Unique Protocol Identification Number
NCT01851070
Brief Title
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
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
July 2013 (Actual)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
March 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mesoblast, Ltd.
Collaborators
PPD

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Normal Saline Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo will be delivered in 100 mL normal saline administered intravenously over approximately 45 minutes.
Arm Title
Allogeneic Mesenchymal Precursor Cells
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Allogeneic Mesenchymal Precursor Cells
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Primary Outcome Measure Information:
Title
Evaluation of the safety of a single IV infusion of allogeneic MPCs compared to placebo at 12 weeks post-infusion
Description
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.
Time Frame
12 weeks post IV Infusion
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
12 weeks post IV infusion with MPCs
Title
Evaluation of long-term safety and efficacy of a singly IV infusion of allogeneic MPCs in patients with active RA
Description
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 outcomes SF36v2 HAQ_DI
Time Frame
52 weeks post IV Infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donna Skerrett, MD, MS
Organizational Affiliation
Mesoblast, Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Research Group
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Arthrocare Arthritis Care and Research PC
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Triwest Research Associates
City
El Cajon
State/Province
California
ZIP/Postal Code
92020
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Inland Rheumatology Clinical Trials Incorporated
City
Upland
State/Province
California
ZIP/Postal Code
91786
Country
United States
Facility Name
Ocala Rheumatology Research Center
City
Ocala
State/Province
Florida
ZIP/Postal Code
34474
Country
United States
Facility Name
Arthritis Center
City
Palm Harbor
State/Province
Florida
ZIP/Postal Code
34684
Country
United States
Facility Name
Sarasota Arthritis Research Center
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
McIlwain Medical Group
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
JHU Arthritis Center Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Arthritis Treatment Center
City
Frederick
State/Province
Maryland
ZIP/Postal Code
21702
Country
United States
Facility Name
Reliant Medical Group
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Office of Ramesh C. Gupta, MD
City
Fair Lawn
State/Province
New Jersey
ZIP/Postal Code
07410
Country
United States
Facility Name
DJL Clinical Research
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Health Research of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73102
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
West Tennessee Research Institute
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
Facility Name
Accurate Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77034
Country
United States
Facility Name
Texas Arthritis Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Southern Clinical Research Pty Ltd
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
Emeritus Research
City
Malvern
State/Province
Victoria
ZIP/Postal Code
3145
Country
Australia

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs