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

NCT02351011 | Completed Phase 1 DMC

• 1 other identifier: MSC-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteoarthritis of Knee

Outcome Measures

Primary Outcomes (1)

• Safety as determined by the occurrence of local and systemic adverse events and/or serious adverse events.

  Safety as determined by the occurrence of local and systemic adverse events and/or serious adverse events.

  1 to 5 years

Secondary Outcomes (10)

• Knee Injury and Osteoarthritis Outcome Score (KOOS)

  1 year

• Marx Activity Scale (Patient-reported activity)

  1 year

• Short-Form 36 (Health-related quality of life)

  1 year

• Whole Organ MRI Score (WORMS), Gadolinium-enhanced MRI, T2 Mapping (To assess joint structure, inflammation, and cartilage status over time)

  1 year

• Cartilage oligomeric matrix protein (COMP)

  1 year

Study Arms (3)

Cohort 1

EXPERIMENTAL

1 x 10\^6 MSCs

Biological: 1 x 10^6 MSCs

Cohort 2

EXPERIMENTAL

10 x 10\^6 MSCs

Biological: 10 x 10^6 MSCs

Cohort 3

EXPERIMENTAL

50 x 10\^6 MSCs

Biological: 50 x 10^6 MSCs

Interventions

1 x 10^6 MSCs BIOLOGICAL

Autologous, bone-marrow derived MSCs

Also known as: Mesenchymal Stromal Cells (MSCs)

Cohort 1

10 x 10^6 MSCs BIOLOGICAL

Autologous, bone-marrow derived MSCs

Also known as: Mesenchymal Stromal Cells (MSCs)

Cohort 2

50 x 10^6 MSCs BIOLOGICAL

Autologous, bone-marrow derived MSCs

Also known as: Mesenchymal Stromal Cells (MSCs)

Cohort 3

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients between 40-65 years of age with symptomatic moderate to severe (Kellgren-Lawrence III or IV) primary osteoarthritis of the knee
• Failed conservative management including physical therapy, bracing and/or oral anti-inflammatories for a minimum of six months
• No history of prior intra-articular cortisone, hyaluronic acid, or platelet-rich plasma injection within the previous six months
• No history of prior arthroscopic knee surgery or open knee surgery on the ipsilateral side within the past year
• Adequate bone marrow, liver, and renal functions
• Body weight \>40 kg
• Body Mass Index \<30
• Negative for (HIV, HTLV1\&2, Hep A, B, C, syphilis) infection as determined by approved serological testing
• 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.
• 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.

You may not qualify if:

• 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
• Patients with varus or valgus malalignment \>5 degrees as measured by 4 foot standing antero-posterior radiographs
• Patients with a history of a previous subtotal medial or lateral meniscectomy
• Patients with a history of septic arthritis in the affected joint
• Patients with a history of a prior intra-articular knee fracture
• Severe bleeding diathesis
• Contraindication to bone marrow aspiration and/or biopsy
• Active infection
• Bone marrow failure
• Cytopenia
• Patients who have previously received radiotherapy to the pelvis
• Patients who have been on chemotherapy from within a year of the date of informed
• Patients with positive serological test for (HIV, HTLV1\&2, Hep A, B, C, syphilis)
• Pregnancy or risk of pregnancy (this includes participants that are not willing to practice active contraception for the duration of the study)
• 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

Sponsors & Collaborators

• Jas Chahal: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Orthopaedic Surgeon

Study Record Dates

• First Submitted: January 20, 2015
• First Posted: January 30, 2015
• Study Start: February 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 27, 2019

Record last verified: 2019-09

Locations

CA (1)