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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Allogeneic Mesenchymal Precursor Cells
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal Saline Placebo<br>Placebo will be delivered in 100 mL normal saline administered intravenously over approximately 45 minutes. | Drug: Allogeneic Mesenchymal Precursor Cells<br> <br> |
| Active Comparator: Allogeneic Mesenchymal Precursor Cells<br>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<br> <br> |

What is the study measuring?
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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 outcomes SF36v2 HAQ_DI | 52 weeks post IV Infusion |