A Phase I/II Study of Chondrogen Delivered by Intra-Articular Injection Following Meniscectomy

A Phase I/II, Randomized, Controlled, Double Blind, Study of Chondrogen - Adult Universal Cell Delivered by Intra-Articular Injection Following Meniscectomy in Patients 18-60 Years

The purpose of this study is to determine whether Chondrogen is a safe and effective post-operative treatment of the knee following menisectomy (the surgical removal of all or part of a torn meniscus).

Study Overview

• Status: Completed
• Conditions: Recovery Following Partial Medial Meniscectomy
• Intervention / Treatment: Drug: Mesenchymal Stem Cells; Drug: Hyaluronan

Detailed Description

Chondrogen is a preparation of adult mesenchymal stem cells (MSCs) in a solution containing hyaluronic acid. Preclinical studies have shown that injection of Chondrogen aids in the repair of meniscal tissue following meniscectomy. In Chondrogen treated subjects, surgically removed meniscal tissue was regenerated, cartilage surface was protected, and joint damage was decreased in comparison to control subjects. These benefits persisted at least one year.

Three groups of recent meniscectomy patients will be followed in this study, including patients that will receive placebo and patients that will be treated with one of two possible doses of Chondrogen.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
  • Florida
    • Vero Beach, Florida, United States, 32960
      • Orthopedic Center of Vero Beach
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Midwest Orthopaedics at Rush
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Ortholndy
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Greater Chesapeake Associates
  • Minnesota
    • Bloomington, Minnesota, United States, 55431
      • TRIA Orthopaedic Center
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Triangle Orthopaedics Associates, P.A.
  • Texas
    • San Antonio, Texas, United States, 78233
      • Unlimited Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 to 60, inclusive
• In need of medial meniscectomy
• Normal axial alignment
• Stable knee- previous ligament reconstruction, if stable
• Removal of at least 50% of the affected portion of the medial meniscus
• Intact articular cartilage in posterior meniscal weight-bearing zone
• Willingness to follow normal post-operative rehabilitation
• Willingness to participate in follow-up for two years from the time of meniscectomy surgery
• Ability to understand and willingness to sign consent form

Exclusion Criteria:

• Pregnant or lactating
• ACL or other support structure damage confirmed at surgery
• Grade III or IV cartilage damage (Cartilage loss greater than 50% thickness in area >15mm on weight-bearing aspect of femoral condyle or tibial plateau)
• Synvisc, steroid, or corticosteroid injections in preceding 3 months
• Diffuse synovitis at time of arthroscopy
• Inflammatory arthritis
• Oral steroid, methotrexate therapy
• Unable to follow post-operative exercise regimen or return for evaluations
• Active alcohol or substance abuse within 6 months of study entry
• Current and active tobacco product use
• Patient is positive for HIV
• Patient is positive for hepatitis (past history of Hepatitis A is allowed)
• Any medical condition, which in the opinion of the clinical investigator, would interfere with the treatment or outcome of the patient
• Indwelling pacemaker
• Cerebral aneurysm clips
• Ear, eye and penile implants with avian components
• Electrical indwelling device such as bone stimulator
• Indwelling magnets as tissue expander for future implants
• Known allergy to avian, bovine or porcine protein

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Chondrogen - dose 1; Chondrogen - 50 million cells	Drug: Mesenchymal Stem Cells
ACTIVE_COMPARATOR: Chondrogen - dose 2; Chondrogen - 150 million cells	Drug: Mesenchymal Stem Cells
OTHER: Vehicle Control	Drug: Hyaluronan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meniscal Volume	Changes in meniscal volume over the course of the study as determined by MRI	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Questionnaire	Determination of Quality of Life will be measured by the KOOS instrument (Knee injury and Osteoarthritis Outcome Score).	2 years
Visual Analog Scale (VAS)	Patient perception of pain will be documented using a single VAS pain scale.	Baseline to 2 years
Lysholm Knee Scale	Lysholm knee score will be determined according to the questionnaire	2 years
Safety Assessment Adverse Event	Number of participants with Adverse Events.	2 years
Safety Assessment Immunological	Number of participants with clinically significant abnormalities in immunological measures	2 years
Safety Assessment Laboratory	Number of participants with clinically significant abnormalities in laboratory assessments	2 years
Safety Assessment Physical Exam	Number of participants with clinically significant abnormalities in physical examinations.	2 years
Safety Assessment Magnetic Resonance Imaging (MRI)	Number of participants with clinically significant abnormalities in Magnetic Resonance Imaging (MRI).	2 years

Collaborators and Investigators

• Sponsor: Mesoblast International Sàrl
• Collaborators: University of Southern California; OrthoIndy; TRIA Orthopaedic Center; Midwest Orthopedics at Rush - Chicago, IL; Unlimited Research - San Antonio, TX; Triangle Orthopaedic Associates, P.A.; Orthopedic Center of Vero Beach - Vero Beach, FL; Greater Chesapeake Orthopaedic Associates, LLC
• Investigators: Study Director: Michelle Williams, Ph.D., Osiris Therapeutics, Inc.

Publications and helpful links

General Publications

• Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284(5411):143-7. doi: 10.1126/science.284.5411.143.
• Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003 Dec;48(12):3464-74. doi: 10.1002/art.11365.
• Vangsness CT Jr, Farr J 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014 Jan 15;96(2):90-8. doi: 10.2106/JBJS.M.00058.

Helpful Links

• Osiris Therapeutics, Inc. Home Page

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): April 1, 2008

Study Registration Dates

• First Submitted: September 21, 2005
• First Submitted That Met QC Criteria: September 21, 2005
• First Posted (ESTIMATE): September 23, 2005

Study Record Updates

• Last Update Posted (ACTUAL): December 27, 2021
• Last Update Submitted That Met QC Criteria: December 23, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; meniscectomy; Osiris; Chondrogen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: Osiris 550