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

Primary Purpose

Osteoarthritis of Knee

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

1 x 10^6 MSCs

10 x 10^6 MSCs

50 x 10^6 MSCs

About this trial

This is an interventional other trial for Osteoarthritis of Knee

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Toronto Western Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Arm Description

1 x 10^6 MSCs

10 x 10^6 MSCs

50 x 10^6 MSCs

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Knee Injury and Osteoarthritis Outcome Score (KOOS)

Knee-joint specific function

Marx Activity Scale (Patient-reported activity)

Patient-reported activity

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

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)

To assess joint structure, inflammation, and cartilage status over time

Cartilage oligomeric matrix protein (COMP)

Serum marker of cartilage metabolism

Hyaluronic acid (HA)

Serum pro-inflammatory marker

C-terminal telopeptide of type II collagen (CTXII)

Urine marker of cartilage metabolism

Types I and II collagen cleavage (C1,2C)

Urine marker of cartilage metabolism

Type II collagen cleavage (C2C)

Urine marker of cartilage metabolism

IL-6/TNFα/IL-15

Synovial fluid pro-inflammatory markers

Full Information

NCT ID

NCT02351011

First Posted

January 20, 2015

Last Updated

September 25, 2019

Sponsor

Jas Chahal

1. Study Identification

Unique Protocol Identification Number

NCT02351011

Brief Title

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

Official Title

Human Autologous Mesenchymal Stromal Cells for the Treatment of Mid to Late Stage Knee Osteoarthritis

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

February 2015 (undefined)

Primary Completion Date

December 2018 (Actual)

Study Completion Date

December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Jas Chahal

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoarthritis of Knee

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1

Arm Type

Experimental

Arm Description

1 x 10^6 MSCs

Arm Title

Cohort 2

Arm Type

Experimental

Arm Description

10 x 10^6 MSCs

Arm Title

Cohort 3

Arm Type

Experimental

Arm Description

50 x 10^6 MSCs

Intervention Type

Biological

Intervention Name(s)

1 x 10^6 MSCs

Other Intervention Name(s)

Mesenchymal Stromal Cells (MSCs)

Intervention Description

Autologous, bone-marrow derived MSCs

Intervention Type

Biological

Intervention Name(s)

10 x 10^6 MSCs

Other Intervention Name(s)

Mesenchymal Stromal Cells (MSCs)

Intervention Description

Autologous, bone-marrow derived MSCs

Intervention Type

Biological

Intervention Name(s)

50 x 10^6 MSCs

Other Intervention Name(s)

Mesenchymal Stromal Cells (MSCs)

Intervention Description

Autologous, bone-marrow derived MSCs

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

1 to 5 years

Secondary Outcome Measure Information:

Title

Knee Injury and Osteoarthritis Outcome Score (KOOS)

Description

Knee-joint specific function

Time Frame

1 year

Title

Marx Activity Scale (Patient-reported activity)

Description

Patient-reported activity

Time Frame

1 year

Title

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

Description

Health-related quality of life

Time Frame

1 year

Title

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

Description

To assess joint structure, inflammation, and cartilage status over time

Time Frame

1 year

Title

Cartilage oligomeric matrix protein (COMP)

Description

Serum marker of cartilage metabolism

Time Frame

1 year

Title

Hyaluronic acid (HA)

Description

Serum pro-inflammatory marker

Time Frame

1 year

Title

C-terminal telopeptide of type II collagen (CTXII)

Description

Urine marker of cartilage metabolism

Time Frame

1 year

Title

Types I and II collagen cleavage (C1,2C)

Description

Urine marker of cartilage metabolism

Time Frame

1 year

Title

Type II collagen cleavage (C2C)

Description

Urine marker of cartilage metabolism

Time Frame

1 year

Title

IL-6/TNFα/IL-15

Description

Synovial fluid pro-inflammatory markers

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jas Chahal, MD, MSc

Organizational Affiliation

Arthritis Program, Toronto Western Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Sowmya Viswanathan, PhD

Organizational Affiliation

Arthritis Program, Toronto Western Hospital & Philip S. Orsino Facility for Cell Therapy

Official's Role

Principal Investigator

Facility Information:

Facility Name

Toronto Western Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5T 2S8

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

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

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