Back to resultsStudy of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee
Primary Purpose
Osteoarthritis, Knee
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TissueGene-C
Normal Saline
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis, Knee focused on measuring Cartilage, Knee, Osteoarthritis
Eligibility Criteria
Inclusion Criteria:
- Male or Female subject
- Age 18 to 70 years
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.
- Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the same for both men and women.
- Blood Pressure measurements - Systolic Blood Pressure should be between 90-160mm. Hg, and Diastolic Blood Pressure between 50-90mm.Hg,
- Patients with Grade 3 chronic osteoarthritis of the knee as determined by the Radiographic Criteria of Kellgren and Lawrence.
- Symptom of pain for more than four (4) consecutive months and intensity of ≥ 40 and ≤ 90 on the 100-mm scale.
- Patients should be cleared to use protocol specified equipment: 3T MRI.
- Patients providing written informed consent after the nature of the study is fully explained and understood by the patient.
Exclusion Criteria:
- Age 71 or older
- Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results.
- Patients taking non-steroidal anti-inflammatory medications within 14 days of baseline visit unless washed out as per section 3.6.4 above.
- Patients taking steroidal anti-inflammatory medications within 2 months of baseline visit.
- Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug test at the time of screening.
- Patients receiving injections to the treated knee within 2 months prior to study entry
- Patients who are contraindicated for 3T MRI.
- Patients who are pregnant or currently breast-feeding children.
- 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.
- Patients with ongoing infectious disease, including HIV and hepatitis B or C.
- Patients with clinically significant cardiovascular, renal, hepatic, endocrine disease, cancer, or Type I diabetes.
- Patients participating in a study of an experimental drug or medical device within 30 days of study entry.
- 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.
Sites / Locations
- Advent Clinical Research
- Sinai Hospital of Baltimore
- Rothman Institute
- University Orthopedics
- Commonwealth Orthopedics
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TissueGene-C
Placebo Control
Arm Description
TissueGene-C at 3 x 10e7 cells per injection (intraarticular)
Normal Saline injection
Outcomes
Primary Outcome Measures
Change From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 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
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.
Secondary Outcome Measures
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 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
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
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
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
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
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
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
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
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
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
Overall assessment of general health as determined by scoring use an SF-36 Questionnaire (Range 0-100 with higher scores better - indicating less disability)
Full Information
NCT ID
NCT01221441
First Posted
October 13, 2010
Last Updated
January 19, 2016
Sponsor
Kolon TissueGene, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01221441
Brief Title
Study of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kolon TissueGene, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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:
Evaluate the efficacy of TissueGene-C with regard to knee functionality and symptoms of knee osteoarthritis including pain.
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.
Evaluate the incidence and dose of analgesia and/or anti-inflammatory medication.
Evaluate the regeneration of hyaline cartilage as determined by 3T magnetic resonance imaging (MRI).
Evaluate distribution of hChonJb#7 cells out of the injection site.
Evaluate the efficacy of TissueGene-C by evaluating the need for total knee arthroplasty after treatment
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis, Knee
Keywords
Cartilage, Knee, Osteoarthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TissueGene-C
Arm Type
Experimental
Arm Description
TissueGene-C at 3 x 10e7 cells per injection (intraarticular)
Arm Title
Placebo Control
Arm Type
Placebo Comparator
Arm Description
Normal Saline injection
Intervention Type
Biological
Intervention Name(s)
TissueGene-C
Other Intervention Name(s)
TG-C
Intervention Description
Single intraarticular injection at 3 x 10e7 cells
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
0.9% Saline
Intervention Description
Single intraarticular injection of normal saline as a placebo control
Primary Outcome Measure Information:
Title
Change From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 1 Year
Description
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.
Time Frame
1 Year
Title
Change From Baseline in Visual Analog Scale (VAS) Score at 1 Year
Description
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.
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 Years
Description
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.
Time Frame
2 Years
Title
Change From Baseline in Articular Cartilage Damage in the Knee as Determined by the Lysholm Knee Score at 2 Years
Description
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.
Time Frame
2 Years
Title
Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) From Baseline to 1 Year
Description
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)
Time Frame
1 Year
Title
Change in Pain Severity From Baseline to 2 Years as Assessed by Questionnaire
Description
Change in pain severity (on a scale from 1 to 4) from baseline to 2 years as measured by a questionnaire (lower scores better)
Time Frame
2 Years
Title
Number of Participants With Change in Pain Severity Measured by Incidence and Dose of Analgesia
Description
The number of participants that had a change in pain severity as measured by the incidence and dose of analgesic medications
Time Frame
2 Years
Title
Change From Baseline in Knee Function as Determined by the Lower Extremity Functional Scale at 2 Years
Description
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)
Time Frame
2 Years
Title
The Incidence of Total Knee Arthroplasty
Description
Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C
Time Frame
2 Years
Title
The Number of Patients Experiencing Injection Site Reactions Related to Treatment
Description
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
Time Frame
2 Years
Title
The Incidence and Severity of Adverse Events in Treated Patients
Description
The incidence and severity of adverse events assessed through 104 weeks (2 years) after dose administration
Time Frame
2 Years
Title
Number of Participants With Adverse Events Due to Clinically Significant Changes in Hematology and Urinalysis Tests
Description
The number of participants with changes in clinical hematology, chemistry, and urinalysis test results through 2 years that were considered Adverse Events
Time Frame
2 Years
Title
Change in SF-36 General Health Assessment Questionnaire (Overall Score) From Baseline to 2 Years
Description
Overall assessment of general health as determined by scoring use an SF-36 Questionnaire (Range 0-100 with higher scores better - indicating less disability)
Time Frame
2 Years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or Female subject
Age 18 to 70 years
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.
Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the same for both men and women.
Blood Pressure measurements - Systolic Blood Pressure should be between 90-160mm. Hg, and Diastolic Blood Pressure between 50-90mm.Hg,
Patients with Grade 3 chronic osteoarthritis of the knee as determined by the Radiographic Criteria of Kellgren and Lawrence.
Symptom of pain for more than four (4) consecutive months and intensity of ≥ 40 and ≤ 90 on the 100-mm scale.
Patients should be cleared to use protocol specified equipment: 3T MRI.
Patients providing written informed consent after the nature of the study is fully explained and understood by the patient.
Exclusion Criteria:
Age 71 or older
Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results.
Patients taking non-steroidal anti-inflammatory medications within 14 days of baseline visit unless washed out as per section 3.6.4 above.
Patients taking steroidal anti-inflammatory medications within 2 months of baseline visit.
Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug test at the time of screening.
Patients receiving injections to the treated knee within 2 months prior to study entry
Patients who are contraindicated for 3T MRI.
Patients who are pregnant or currently breast-feeding children.
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.
Patients with ongoing infectious disease, including HIV and hepatitis B or C.
Patients with clinically significant cardiovascular, renal, hepatic, endocrine disease, cancer, or Type I diabetes.
Patients participating in a study of an experimental drug or medical device within 30 days of study entry.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael A Mont, MD
Organizational Affiliation
Sinai Hospital of Baltimore
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David W Romness, MD
Organizational Affiliation
Commonwealth Orthopedics, Virginia Hospital Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Advent Clinical Research
City
Pinellas Park
State/Province
Florida
ZIP/Postal Code
33781
Country
United States
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Rothman Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University Orthopedics
City
State College
State/Province
Pennsylvania
ZIP/Postal Code
16801
Country
United States
Facility Name
Commonwealth Orthopedics
City
Arlington
State/Province
Virginia
ZIP/Postal Code
22205
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29145839
Citation
Guermazi A, Kalsi G, Niu J, Crema MD, Copeland RO, Orlando A, Noh MJ, Roemer FW. Structural effects of intra-articular TGF-beta1 in moderate to advanced knee osteoarthritis: MRI-based assessment in a randomized controlled trial. BMC Musculoskelet Disord. 2017 Nov 16;18(1):461. doi: 10.1186/s12891-017-1830-8.
Results Reference
derived
PubMed Identifier
26188189
Citation
Cherian JJ, Parvizi J, Bramlet D, Lee KH, Romness DW, Mont MA. Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-beta1 in patients with grade 3 chronic degenerative joint disease of the knee. Osteoarthritis Cartilage. 2015 Dec;23(12):2109-2118. doi: 10.1016/j.joca.2015.06.019. Epub 2015 Jul 16.
Results Reference
derived
Learn more about this trial
Study of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee
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