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Human Autologous MSCs for the Treatment of Mid to Late Stage Knee OA

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ClinicalTrials.gov Identifier: NCT02351011
Recruitment Status : Active, not recruiting
First Posted : January 30, 2015
Last Update Posted : May 1, 2018
Sponsor:
Information provided by (Responsible Party):
Jas Chahal, University Health Network, Toronto

January 20, 2015
January 30, 2015
May 1, 2018
February 2015
December 2018   (Final data collection date for primary outcome measure)
Safety as determined by the occurrence of local and systemic adverse events and/or serious adverse events. [ Time Frame: 1 to 5 years ]
Safety as determined by the occurrence of local and systemic adverse events and/or serious adverse events.
Same as current
Complete list of historical versions of study NCT02351011 on ClinicalTrials.gov Archive Site
  • Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: 1 year ]
    Knee-joint specific function
  • Marx Activity Scale (Patient-reported activity) [ Time Frame: 1 year ]
    Patient-reported activity
  • Short-Form 36 (Health-related quality of life) [ Time Frame: 1 year ]
    Health-related quality of life
  • Whole Organ MRI Score (WORMS), Gadolinium-enhanced MRI, T2 Mapping (To assess joint structure, inflammation, and cartilage status over time) [ Time Frame: 1 year ]
    To assess joint structure, inflammation, and cartilage status over time
  • Cartilage oligomeric matrix protein (COMP) [ Time Frame: 1 year ]
    Serum marker of cartilage metabolism
  • Hyaluronic acid (HA) [ Time Frame: 1 year ]
    Serum pro-inflammatory marker
  • C-terminal telopeptide of type II collagen (CTXII) [ Time Frame: 1 year ]
    Urine marker of cartilage metabolism
  • Types I and II collagen cleavage (C1,2C) [ Time Frame: 1 year ]
    Urine marker of cartilage metabolism
  • Type II collagen cleavage (C2C) [ Time Frame: 1 year ]
    Urine marker of cartilage metabolism
  • IL-6/TNFα/IL-15 [ Time Frame: 1 year ]
    Synovial fluid pro-inflammatory markers
Same as current
Not Provided
Not Provided
 
Human Autologous MSCs for the Treatment of Mid to Late Stage Knee OA
Human Autologous Mesenchymal Stromal Cells for the Treatment of Mid to Late Stage Knee Osteoarthritis

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Osteoarthritis of Knee
  • Biological: 1 x 10^6 MSCs
    Autologous, bone-marrow derived MSCs
    Other Name: Mesenchymal Stromal Cells (MSCs)
  • Biological: 10 x 10^6 MSCs
    Autologous, bone-marrow derived MSCs
    Other Name: Mesenchymal Stromal Cells (MSCs)
  • Biological: 50 x 10^6 MSCs
    Autologous, bone-marrow derived MSCs
    Other Name: Mesenchymal Stromal Cells (MSCs)
  • Experimental: Cohort 1
    1 x 10^6 MSCs
    Intervention: Biological: 1 x 10^6 MSCs
  • Experimental: Cohort 2
    10 x 10^6 MSCs
    Intervention: Biological: 10 x 10^6 MSCs
  • Experimental: Cohort 3
    50 x 10^6 MSCs
    Intervention: Biological: 50 x 10^6 MSCs
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
12
Same as current
December 2018
December 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients between 40-65 years of age with symptomatic moderate to severe (Kellgren-Lawrence III or IV) primary osteoarthritis of the knee
  2. Failed conservative management including physical therapy, bracing and/or oral anti-inflammatories for a minimum of six months
  3. No history of prior intra-articular cortisone, hyaluronic acid, or platelet-rich plasma injection within the previous six months
  4. No history of prior arthroscopic knee surgery or open knee surgery on the ipsilateral side within the past year
  5. Adequate bone marrow, liver, and renal functions
  6. Body weight >40 kg
  7. Body Mass Index <30
  8. Negative for (HIV, HTLV1&2, Hep A, B, C, syphilis) infection as determined by approved serological testing
  9. Negative for pregnancy as determined by a serum pregnancy test. Females of childbearing potential will be required to practice abstinence or use an effective form of contraception for 12 months following their MSC injection.
  10. Fluid > 1 cm within the lateral recess of the suprapatellar pouch at the level of the superior pole of the patella with the knee extended.

Exclusion Criteria:

  1. Patients with clinically unstable knee due to the presence of a complete anterior cruciate ligament, posterior cruciate ligament, medial collateral ligament and/or posterolateral corner tear
  2. Patients with varus or valgus malalignment >5 degrees as measured by 4 foot standing antero-posterior radiographs
  3. Patients with a history of a previous subtotal medial or lateral meniscectomy
  4. Patients with a history of septic arthritis in the affected joint
  5. Patients with a history of a prior intra-articular knee fracture
  6. Severe bleeding diathesis
  7. Contraindication to bone marrow aspiration and/or biopsy
  8. Active infection
  9. Bone marrow failure
  10. Cytopenia
  11. Patients who have previously received radiotherapy to the pelvis
  12. Patients who have been on chemotherapy from within a year of the date of informed
  13. Patients with positive serological test for (HIV, HTLV1&2, Hep A, B, C, syphilis)
  14. Pregnancy or risk of pregnancy (this includes participants that are not willing to practice active contraception for the duration of the study)
  15. Patients with unforeseen conditions that are deemed unsafe or inappropriate for the study (e.g. patients who are claustrophobic and cannot undergo an MRI) as per the discretion of the principal investigator
Sexes Eligible for Study: All
40 Years to 65 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
 
NCT02351011
MSC-001
Yes
Not Provided
Not Provided
Jas Chahal, University Health Network, Toronto
Jas Chahal
Not Provided
Principal Investigator: Jas Chahal, MD, MSc Arthritis Program, Toronto Western Hospital
Principal Investigator: Sowmya Viswanathan, PhD Arthritis Program, Toronto Western Hospital & Philip S. Orsino Facility for Cell Therapy
University Health Network, Toronto
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP