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

Sponsor

Mesoblast, Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT01851070

Collaborator

PPD (Industry)

Enrollment

Locations

Arms

Actual Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Allogeneic Mesenchymal Precursor Cells Drug: Normal Saline	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 1, 2013

Actual Primary Completion Date :

May 1, 2016

Actual Study Completion Date :

Mar 1, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Evaluation of the safety of a single IV infusion of allogeneic MPCs compared to placebo at 12 weeks post-infusion [12 weeks post IV 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 [12 weeks post IV infusion with MPCs]
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 [52 weeks post IV Infusion]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

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

Sponsors and Collaborators

Mesoblast, Ltd.
PPD

Investigators

Study Director: Donna Skerrett, MD, MS, Mesoblast, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Mesoblast, Ltd.

ClinicalTrials.gov Identifier:

NCT01851070

Other Study ID Numbers:

MSB-RA001

First Posted:

May 10, 2013

Last Update Posted:

Jun 26, 2020

Last Verified:

Jun 1, 2020

Additional relevant MeSH terms:

Arthritis

Arthritis, Rheumatoid

Study Results

No Results Posted as of Jun 26, 2020