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Study of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee

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ClinicalTrials.gov Identifier: NCT01221441
Recruitment Status : Completed
First Posted : October 15, 2010
Results First Posted : February 15, 2016
Last Update Posted : February 15, 2016
Sponsor:
Information provided by (Responsible Party):
Kolon TissueGene, Inc.

Tracking Information
First Submitted Date  ICMJE October 13, 2010
First Posted Date  ICMJE October 15, 2010
Results First Submitted Date  ICMJE November 5, 2015
Results First Posted Date  ICMJE February 15, 2016
Last Update Posted Date February 15, 2016
Study Start Date  ICMJE May 2011
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2016)
  • Change From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 1 Year [ Time Frame: 1 Year ]
    Symptoms, pain and function of the knee joint determined and scored using the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation (Total Score, range 0-100 with higher scores better). Linear mixed model used for analysis.
  • Change From Baseline in Visual Analog Scale (VAS) Score at 1 Year [ Time Frame: 1 Year ]
    Reduction in pain as measured by a 100 mm visual analog scale (0= no pain; 100 = extreme pain) from Baseline to 1 Year. Linear mixed model used for analysis.
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2010)
  • Knee Symptoms, Pain and Function Determined by the International Knee Documentation Committee (IKDC) Subjective Knee Evalution [ Time Frame: 1 Year ]
    Symptoms, pain and function of the knee joint will be determined and scored using the IKDC Subjective Knee Evaluation
  • Reduction in Pain as Determined by a Visual Analog Scale (VAS) [ Time Frame: 1 Year ]
    Reduction in pain as measured by a 100 mm visual analog scale
Change History Complete list of historical versions of study NCT01221441 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2016)
  • Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 Years [ Time Frame: 2 Years ]
    Symptoms, pain and functionality of the knee joint as determined by Total Score of the Knee Injury and Osteoarthritis Outcome Score (KOOS) (Range 0-100 with higher scores indicating healthier outcomes). Linear mixed model used for analysis.
  • Change From Baseline in Articular Cartilage Damage in the Knee as Determined by the Lysholm Knee Score at 2 Years [ Time Frame: 2 Years ]
    Measurement to assess outcomes of various chondral disorders of the knee determined by the Lysholm Knee Scale (Range 0-100 with higher scores better). Linear mixed model used for analysis.
  • Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) From Baseline to 1 Year [ Time Frame: 1 Year ]
    Comparison of pre-procedure 3T MRI scans to those obtained at months 12 following dose administration by an independent radiographic reviewer. Evaluations will be scored using Whole Organ Magnetic Resonance imaging Score (WORMS) Cartilage Morphology Subscore (Range 0-6, with higher scores being worse)
  • Change in Pain Severity From Baseline to 2 Years as Assessed by Questionnaire [ Time Frame: 2 Years ]
    Change in pain severity (on a scale from 1 to 4) from baseline to 2 years as measured by a questionnaire (lower scores better)
  • Number of Participants With Change in Pain Severity Measured by Incidence and Dose of Analgesia [ Time Frame: 2 Years ]
    The number of participants that had a change in pain severity as measured by the incidence and dose of analgesic medications
  • Change From Baseline in Knee Function as Determined by the Lower Extremity Functional Scale at 2 Years [ Time Frame: 2 Years ]
    Assessment of knee function as determined by the Lower Extremity Functional Scale (LEFS); change from baseline to 2 years (Range 0-80 with higher scores signifying lower difficulty in performing knee functions)
  • The Incidence of Total Knee Arthroplasty [ Time Frame: 2 Years ]
    Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C
  • The Number of Patients Experiencing Injection Site Reactions Related to Treatment [ Time Frame: 2 Years ]
    The number of patients with observations of the administration site deemed related to treatment with either active or placebo, including arthralgia, swelling, irritation, pain, stiffness or abnormalities
  • The Incidence and Severity of Adverse Events in Treated Patients [ Time Frame: 2 Years ]
    The incidence and severity of adverse events assessed through 104 weeks (2 years) after dose administration
  • Number of Participants With Adverse Events Due to Clinically Significant Changes in Hematology and Urinalysis Tests [ Time Frame: 2 Years ]
    The number of participants with changes in clinical hematology, chemistry, and urinalysis test results through 2 years that were considered Adverse Events
  • Change in SF-36 General Health Assessment Questionnaire (Overall Score) From Baseline to 2 Years [ Time Frame: 2 Years ]
    Overall assessment of general health as determined by scoring use an SF-36 Questionnaire (Range 0-100 with higher scores better - indicating less disability)
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2010)
  • Knee Symptoms, Pain and Functionality as Determined by the Knee Injury and Osteoarthritis Outcome Score(KOOS) [ Time Frame: 2 Years ]
    Symptoms, pain and functionality of the knee joint as determined by Knee Injury and Osteoarthritis Outcome Score (KOOS)
  • Articular Cartilage Damage in the Knee as Determined by the Lysholm Knee Score [ Time Frame: 2 Years ]
    Articular cartilage damage in the knee will be measured by the Lysholm Knee Scale
  • Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) [ Time Frame: 1 Year ]
    Comparison of pre-procedure 3T MRI scans to those obtained at months 3, 6, and 12 following dose administration by an independent radiographic reviewer. Evaluations will be scored using Whole Organ Magnetic Resonance imaginge Score (WORMS) and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART).
  • Pain reduction assessed by medication usage [ Time Frame: 2 Years ]
    Reduction in pain as measured by a questionnaire and the incidence and dose of analgesia.
  • Anti-inflammatory Medication Usage [ Time Frame: 2 Years ]
    The incidence and dose of anti-inflammatory medications
  • Knee Function as Determined by the Lower Extremity Functional Scale [ Time Frame: 2 Years ]
    Assessment of knee function as determined by the Lower Extremity Functional Scale (LEFS)
  • The Incidence of Total Knee Arthroplasty [ Time Frame: 2 Years ]
    Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C
  • The Incidence and Severity of Injection Site Reactions [ Time Frame: 2 Years ]
    The incidence and severity of observations of the administration site including swelling, irritation, immune reaction or other abnormalities
  • The Incidence and Severity of Adverse Events in Treated Patients [ Time Frame: 2 Years ]
    The incidence and severity of adverse events assessed through 730 days (24 months) after dose administration
  • Clinically Significant Changes in Hematology and Urinalysis Parameters [ Time Frame: 2 Years ]
    The changes in clinical hematology, chemistry, and urinalysis test results at each time point from dose administration through day 730 (24 months).
  • General Health as Determined by a Validated Standardized Questionnaire [ Time Frame: 2 Years ]
    A SF-36 Questionnaire will be completed by subjects every six months (Baseline Visit and 6, 12, 18, and 24 month visits)
  • International Cartilage Repair Society (ICRS) Histological Scoring of Resected Knee Tissue [ Time Frame: 2 Years ]
    For those patients undergoing a total knee arthroplasty procedure during the study period, the resected knee tissue will undergo histological analysis and scored according to the ICRS scoring system (Mainil-Varlet et al., 2003).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee
Official Title  ICMJE A Phase II Study to Determine the Efficacy and Safety of Allogeneic Human Chondrocytes Expressing TGF-β1 (TissueGene-C) in Patients With Grade 3 Chronic Degenerative Joint Disease of the Knee
Brief Summary The purpose of this study is to see if we can safely regenerate cartilage without invasive surgery using a biologic product called TissueGene-C.
Detailed Description

Protocol TGC09201 is a multi-center, double-blind, placebo-controlled, randomized study. A total of one hundred (100) adults with grade 3 chronic degenerative joint disease (DJD) of the knee joint (as determined by radiographic examination) will be enrolled into the study. TissueGene-C will be administered intra-articularly once via x-ray guidance. TissueGene-C will be administered at a dose of 3 x 10e7 cells. Patients receiving control treatment will receive a single normal saline injection.

The objectives of this study are to:

  1. Evaluate the efficacy of TissueGene-C with regard to knee functionality and symptoms of knee osteoarthritis including pain.
  2. Evaluate the safety of administration of a single intra-articular dose of TissueGene-C as evidenced by observation of the injection site for irritation or other abnormalities, the incidence and severity of adverse events, and the changes in physical examination findings and laboratory tests, including immune analyses.
  3. Evaluate the incidence and dose of analgesia and/or anti-inflammatory medication.
  4. Evaluate the regeneration of hyaline cartilage as determined by 3T magnetic resonance imaging (MRI).
  5. Evaluate distribution of hChonJb#7 cells out of the injection site.
  6. Evaluate the efficacy of TissueGene-C by evaluating the need for total knee arthroplasty after treatment
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Osteoarthritis, Knee
Intervention  ICMJE
  • Biological: TissueGene-C
    Single intraarticular injection at 3 x 10e7 cells
    Other Name: TG-C
  • Drug: Normal Saline
    Single intraarticular injection of normal saline as a placebo control
    Other Name: 0.9% Saline
Study Arms  ICMJE
  • Experimental: TissueGene-C
    TissueGene-C at 3 x 10e7 cells per injection (intraarticular)
    Intervention: Biological: TissueGene-C
  • Placebo Comparator: Placebo Control
    Normal Saline injection
    Intervention: Drug: Normal Saline
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 9, 2014)
102
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2010)
100
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or Female subject
  2. Age 18 to 70 years
  3. In general good health as evidenced by physical examination, normal hematology, serum chemistry, and urinalysis screening laboratory results, and a negative history of significant organ system disorders. All laboratory values must be within 20% of normal ranges.

    1. Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the same for both men and women.
    2. Blood Pressure measurements - Systolic Blood Pressure should be between 90-160mm. Hg, and Diastolic Blood Pressure between 50-90mm.Hg,
  4. Patients with Grade 3 chronic osteoarthritis of the knee as determined by the Radiographic Criteria of Kellgren and Lawrence.
  5. Symptom of pain for more than four (4) consecutive months and intensity of ≥ 40 and ≤ 90 on the 100-mm scale.
  6. Patients should be cleared to use protocol specified equipment: 3T MRI.
  7. Patients providing written informed consent after the nature of the study is fully explained and understood by the patient.

Exclusion Criteria:

  1. Age 71 or older
  2. Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results.
  3. Patients taking non-steroidal anti-inflammatory medications within 14 days of baseline visit unless washed out as per section 3.6.4 above.
  4. Patients taking steroidal anti-inflammatory medications within 2 months of baseline visit.
  5. Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug test at the time of screening.
  6. Patients receiving injections to the treated knee within 2 months prior to study entry
  7. Patients who are contraindicated for 3T MRI.
  8. Patients who are pregnant or currently breast-feeding children.
  9. Patients with systemic, rheumatic or inflammatory disease of the knee or chondrocalcinosis, hemochromatosis, inflammatory arthritis, necrosis of the femoral condyle, arthropathy of the knee associated with juxta-articular Paget's disease of the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's knee joint, villonodular synovitis, synovial chondromatosis, and/or history of inflammatory arthropathy.
  10. Patients with ongoing infectious disease, including HIV and hepatitis B or C.
  11. Patients with clinically significant cardiovascular, renal, hepatic, endocrine disease, cancer, or Type I diabetes.
  12. Patients participating in a study of an experimental drug or medical device within 30 days of study entry.
  13. Patients that will be unable to comply with the requisite study follow-up and are not able to complete all of the follow-up office visits and 3T MRI exams.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01221441
Other Study ID Numbers  ICMJE TGC09201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kolon TissueGene, Inc.
Study Sponsor  ICMJE Kolon TissueGene, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael A Mont, MD Sinai Hospital of Baltimore
Principal Investigator: David W Romness, MD Commonwealth Orthopedics, Virginia Hospital Center
PRS Account Kolon TissueGene, Inc.
Verification Date January 2016

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