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

Mesoblast

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Allogeneic Mesenchymal Precursor Cells; Drug: Normal Saline

Study type: Interventional

Funder types: Industry

Identifiers

NCT01851070

MSB-RA001

Details and patient eligibility

About

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.

Enrollment: 48 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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48 participants in 2 patient groups, including a placebo group

Normal Saline Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Allogeneic Mesenchymal Precursor Cells

Allogeneic Mesenchymal Precursor Cells

Active Comparator group

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.

Treatment:

Drug: Normal Saline