Human Autologous MSCs for the Treatment of Mid to Late Stage Knee OA
Condition: Osteoarthritis of Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Osteoarthritis (OA) is one of the most common forms of arthritis. It is a lasting condition
      in which the material that cushions the joints, called cartilage, breaks down. This causes
      the bones to rub against each other, causing inflammation, stiffness, pain and loss of joint
      movement. Currently, there are few effective treatments available for patients suffering from
      OA.

      Mesenchymal stem cells (MSCs) are cells that have the ability to self-regenerate, which means
      they have the ability to make copies of themselves and to turn into other kinds of cells
      (e.g. cartilage cells). Stem cell science shows much promise for the future treatment of
      osteoarthritis, but much of the research is still in the early stages. In this study,
      researchers want to determine the safety of MSCs that a patient can tolerate without causing
      side effects. This will be done by starting at a low dose of MSCs and moving on to the next
      higher dose level provided there are no safety concerns. Researchers will also be looking at
      the function of the knee over time, which may give them some insight on the usefulness of
      MSCs as a treatment option.
    

Detailed description: 
      The trial is a non-randomized, open-label, dose escalation phase I/II clinical trial. A total
      of 12 participants will be enrolled - patients will be treated in cohorts of 3 to determine
      the safety and preliminary efficacy of autologous, ex-vivo expanded bone-marrow derived MSC
      injected into the knee joint in patients with moderate to advanced knee osteoarthritis.

      A minimum of three evaluable patients will be entered at each dose level until the maximum
      tolerated dose (MTD) is reached. Toxicity will be evaluated and graded according to the
      Common Terminology Criteria (CTC) for Adverse Events, as Grade 3-4. If a patient is
      discontinued due to a grade 3 or 4 adverse event (i.e. dose-limiting toxicity, DLT), an
      additional patient will be enrolled at the same dose level to ensure that a minimum of 3
      patients are evaluated. If 0/3 patients experience dose-limiting (DLT) at a given dose level,
      then the dose will be escalated for next cohort of 3 patients. If 1/3 patients experience DLT
      at a given dose level, then an additional 3 patients will be treated at that dose level. If
      no other patient experiences a DLT, dose escalation will continue. If DLT occurs in 2/3 or
      2/6 patients, dose escalation will stop and the prior dose level will be declared the MTD for
      the MSC cell infusions in this study.
    

Intervention name(s): 1 x 10^6 MSCs; 10 x 10^6 MSCs; 50 x 10^6 MSCs
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Autologous, bone-marrow derived MSCs; Autologous, bone-marrow derived MSCs; Autologous, bone-marrow derived MSCs
Other intervention name(s): Mesenchymal Stromal Cells (MSCs); Mesenchymal Stromal Cells (MSCs); Mesenchymal Stromal Cells (MSCs)
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other