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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01851070
• Other study ID #: MSB-RA001
• Status: Completed
• Phase: Phase 2
• Start date: July 2013
• Est. completion date: March 2017

Study information

• Verified date: June 2020
• Source: Mesoblast, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: March 2017
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 TNFa 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 TNFa 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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Allogeneic Mesenchymal Precursor Cells

• Normal Saline

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Southern Clinical Research Pty Ltd	Hobart	Tasmania
Australia	Emeritus Research	Malvern	Victoria
United States	Pinnacle Research Group	Anniston	Alabama
United States	JHU Arthritis Center Baltimore	Baltimore	Maryland
United States	DJL Clinical Research	Charlotte	North Carolina
United States	Triwest Research Associates	El Cajon	California
United States	Office of Ramesh C. Gupta, MD	Fair Lawn	New Jersey
United States	Arthritis Treatment Center	Frederick	Maryland
United States	Arthrocare Arthritis Care and Research PC	Gilbert	Arizona
United States	Accurate Clinical Research	Houston	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	UCLA	Los Angeles	California
United States	Ocala Rheumatology Research Center	Ocala	Florida
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Arthritis Center	Palm Harbor	Florida
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Texas Arthritis Research Center	San Antonio	Texas
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	McIlwain Medical Group	Tampa	Florida
United States	Inland Rheumatology Clinical Trials Incorporated	Upland	California
United States	Reliant Medical Group	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Mesoblast, Ltd.	PPD

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 TNFa 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	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 TNFa inhibitor.	12 weeks post IV infusion with MPCs
Secondary	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 TNFa 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	52 weeks post IV Infusion