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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.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Osteoarthritis, Knee
Interventions Biological: TissueGene-C
Drug: Normal Saline
Enrollment 102
Recruitment Details  
Pre-assignment Details  
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Period Title: Overall Study
Started 67 35
Completed 45 23
Not Completed 22 12
Arm/Group Title TissueGene-C Placebo Control Total
Hide Arm/Group Description

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Total of all reporting groups
Overall Number of Baseline Participants 67 35 102
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 35 participants 102 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
39
  58.2%
20
  57.1%
59
  57.8%
>=65 years
28
  41.8%
15
  42.9%
43
  42.2%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 35 participants 102 participants
56.7  (7.89) 56.5  (8.62) 56.6  (8.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 35 participants 102 participants
Female
43
  64.2%
21
  60.0%
64
  62.7%
Male
24
  35.8%
14
  40.0%
38
  37.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 67 participants 35 participants 102 participants
Caucasian/White 53 29 82
Black 12 4 16
Hispanic 2 2 4
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 67 participants 35 participants 102 participants
67 35 102
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 67 participants 35 participants 102 participants
29.6  (5.87) 29.6  (5.62) 29.6  (5.70)
1.Primary Outcome
Title Change From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 1 Year
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with available baseline IKDC scores
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 38 20
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
23.3
(17.3 to 29.3)
9.9
(1.7 to 18.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TissueGene-C, Placebo Control
Comments

The primary efficacy evaluation based on IKDC and the VAS were tested at week 52 evaluated 100 mm VAS with the following superiority hypothesis:

HO: μTG = μPC vs. HA: μTG ≠ μPC, where μTG and μPC are the mean change from baseline in IKDC or VAS scores at week 52 for patients in the TG-C and placebo control groups, respectively. If the null hypotheses for both the IKDC and the VAS are rejected, it the clinical effect of TG-C is concluded to be superior to that of the control.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Mixed Models Analysis
Comments Denominator degrees of freedom were adjusted using the Kenward-Roger’s method.
2.Primary Outcome
Title Change From Baseline in Visual Analog Scale (VAS) Score at 1 Year
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with available baseline and 1 year VAS score
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 49 24
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-39.7
(-46.7 to -32.7)
-24.3
(-34.1 to -14.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TissueGene-C, Placebo Control
Comments

The primary efficacy evaluation based on IKDC and the VAS were tested at week 52 evaluated 100 mm VAS with the following superiority hypothesis:

HO: μTG = μPC vs. HA: μTG ≠ μPC, where μTG and μPC are the mean change from baseline in IKDC or VAS scores at week 52 for patients in the TG-C and placebo control groups, respectively. If the null hypotheses for both the IKDC and the VAS are rejected, it the clinical effect of TG-C is concluded to be superior to that of the control.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Mixed Models Analysis
Comments Denominator degrees of freedom were adjusted using the Kenward-Roger’s method.
3.Secondary Outcome
Title Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 Years
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 45 23
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
10.0
(6.0 to 13.9)
10.5
(5.0 to 16.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TissueGene-C, Placebo Control
Comments

The efficacy evaluation at week 104 evaluated KOOS with the following superiority hypothesis:

HO: μTG = μPC vs. HA: μTG ≠ μPC, where μTG and μPC are the mean change from baseline in KOOS scores at week 104 for patients in the TG-C and placebo control groups, respectively. If the null hypotheses for KOOS is rejected, it the clinical effect of TG-C is concluded to be superior to that of the control.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Mixed Models Analysis
Comments Denominator degrees of freedom were adjusted using the Kenward-Roger’s method.
4.Secondary Outcome
Title Change From Baseline in Articular Cartilage Damage in the Knee as Determined by the Lysholm Knee Score at 2 Years
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 45 23
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
20.1
(14.8 to 25.5)
11.4
(4.1 to 18.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TissueGene-C, Placebo Control
Comments

The efficacy evaluation at week 104 evaluated Lysholm score with the following superiority hypothesis:

HO: μTG = μPC vs. HA: μTG ≠ μPC, where μTG and μPC are the mean change from baseline in KOOS scores at week 104 for patients in the TG-C and placebo control groups, respectively. If the null hypotheses for Lysholm score is rejected, it the clinical effect of TG-C is concluded to be superior to that of the control.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Mixed Models Analysis
Comments Denominator degrees of freedom were adjusted using the Kenward-Roger’s method.
5.Secondary Outcome
Title Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) From Baseline to 1 Year
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with available baseline and 1-year MRIs
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 32 22
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
0.03
(-1.22 to 1.29)
-0.49
(-2.07 to 1.08)
6.Secondary Outcome
Title Change in Pain Severity From Baseline to 2 Years as Assessed by Questionnaire
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that completed 2 year follow-up
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 33 18
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-0.87  (0.844) -0.30  (1.031)
7.Secondary Outcome
Title Number of Participants With Change in Pain Severity Measured by Incidence and Dose of Analgesia
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients taking at least one analgesia medication
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 67 35
Measure Type: Number
Unit of Measure: participants
37 20
8.Secondary Outcome
Title Change From Baseline in Knee Function as Determined by the Lower Extremity Functional Scale at 2 Years
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that completed 2-year follow-up
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 45 23
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
16.7
(11.9 to 21.5)
13.8
(7.1 to 20.4)
9.Secondary Outcome
Title The Incidence of Total Knee Arthroplasty
Hide Description Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C
Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that participated in the study
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 67 35
Measure Type: Number
Unit of Measure: participants
1 1
10.Secondary Outcome
Title The Number of Patients Experiencing Injection Site Reactions Related to Treatment
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants receiving placebo or active treatment
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 67 35
Measure Type: Number
Unit of Measure: participants
35 5
11.Secondary Outcome
Title The Incidence and Severity of Adverse Events in Treated Patients
Hide Description The incidence and severity of adverse events assessed through 104 weeks (2 years) after dose administration
Time Frame 2 Years
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving treatment with either active or placebo
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 67 35
Measure Type: Number
Unit of Measure: participants
Mild 12 7
Moderate 41 18
Severe 8 4
12.Secondary Outcome
Title Number of Participants With Adverse Events Due to Clinically Significant Changes in Hematology and Urinalysis Tests
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All patients
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 67 35
Measure Type: Number
Unit of Measure: participants
17 5
13.Secondary Outcome
Title Change in SF-36 General Health Assessment Questionnaire (Overall Score) From Baseline to 2 Years
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with completed SF-36 questionnaire at 104 weeks
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description:

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

Overall Number of Participants Analyzed 45 22
Least Squares Mean (95% Confidence Interval)
Unit of Measure: scores on a scale
7.6
(4.4 to 10.8)
6.7
(2.2 to 11.2)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TissueGene-C Placebo Control
Hide Arm/Group Description

TissueGene-C at 3 x 10e7 cells per injection (intraarticular)

TissueGene-C: Single intraarticular injection at 3 x 10e7 cells

Normal Saline injection

Normal Saline: Single intraarticular injection of normal saline as a placebo control

All-Cause Mortality
TissueGene-C Placebo Control
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
TissueGene-C Placebo Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/67 (10.45%)      4/35 (11.43%)    
Gastrointestinal disorders     
Gastritis   1/67 (1.49%)  1 0/35 (0.00%)  0
Abdominal Pain   1/67 (1.49%)  1 0/35 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain   2/67 (2.99%)  2 0/35 (0.00%)  0
Radius Fracture   1/67 (1.49%)  1 0/35 (0.00%)  0
Hiatal hernia   1/67 (1.49%)  1 0/35 (0.00%)  0
Invertebral Disc Protrusion   1/67 (1.49%)  1 0/35 (0.00%)  0
Microdiscectomy   1/67 (1.49%)  1 0/35 (0.00%)  0
Lumbar spinal stenosis   1/67 (1.49%)  1 0/35 (0.00%)  0
Musculoskeletal Chest Pain   1/67 (1.49%)  1 0/35 (0.00%)  0
Spinal Column Stenosis   1/67 (1.49%)  1 0/35 (0.00%)  0
Lumbar Degenerative Disc Disease   0/67 (0.00%)  0 1/35 (2.86%)  1
Nervous system disorders     
Sciatica   2/67 (2.99%)  2 0/35 (0.00%)  0
Paraesthesia   1/67 (1.49%)  1 0/35 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism   0/67 (0.00%)  0 1/35 (2.86%)  1
Surgical and medical procedures     
Total Knee Arthroplasty   2/67 (2.99%)  2 1/35 (2.86%)  1
Prostatectomy   0/67 (0.00%)  0 1/35 (2.86%)  1
Spinal Fusion Surgery   1/67 (1.49%)  1 1/35 (2.86%)  1
Spinal Laminectomy   1/67 (1.49%)  1 1/35 (2.86%)  1
Invertebral Disc Operation   1/67 (1.49%)  1 0/35 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
TissueGene-C Placebo Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/67 (67.16%)      8/35 (22.86%)    
Gastrointestinal disorders     
Nausea   1/67 (1.49%)  1 0/35 (0.00%)  0
General disorders     
Chills   1/67 (1.49%)  1 0/35 (0.00%)  0
Fatigue   1/67 (1.49%)  1 0/35 (0.00%)  0
Feeling Cold   1/67 (1.49%)  1 0/35 (0.00%)  0
Pain   1/67 (1.49%)  1 0/35 (0.00%)  0
Asthenia   0/67 (0.00%)  0 1/35 (2.86%)  1
Investigations     
C-reactive Protein Increased   1/67 (1.49%)  1 0/35 (0.00%)  0
Eosinophil Count Increased   1/67 (1.49%)  1 0/35 (0.00%)  0
Interleukin Level Increased   5/67 (7.46%)  5 1/35 (2.86%)  1
Red Blood Cell Sedimentation Increased   2/67 (2.99%)  2 1/35 (2.86%)  1
Increased White Blood Cells/Neutrophils   1/67 (1.49%)  1 0/35 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia   15/67 (22.39%)  15 2/35 (5.71%)  2
Arthritis   19/67 (28.36%)  19 1/35 (2.86%)  1
Arthropathy   1/67 (1.49%)  1 0/35 (0.00%)  0
Joint Effusions   13/67 (19.40%)  13 2/35 (5.71%)  2
Muscular Weakness   1/67 (1.49%)  1 0/35 (0.00%)  0
Pain in Extremity   1/67 (1.49%)  1 0/35 (0.00%)  0
Weight Bearing Difficulty   5/67 (7.46%)  5 0/35 (0.00%)  0
Right Knee Swelling   1/67 (1.49%)  1 0/35 (0.00%)  0
Nervous system disorders     
Presyncope   1/67 (1.49%)  1 0/35 (0.00%)  0
Syncope   1/67 (1.49%)  1 0/35 (0.00%)  0
Skin and subcutaneous tissue disorders     
Eczema   1/67 (1.49%)  1 0/35 (0.00%)  0
Hair Growth Abnormal   1/67 (1.49%)  1 0/35 (0.00%)  0
Skin Warm   1/67 (1.49%)  1 0/35 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: R. Ogden Copeland
Organization: TissueGene, Inc
Phone: (301) 921-6000 ext 122
EMail: ocopeland@tissuegene.com
Layout table for additonal information
Responsible Party: Kolon TissueGene, Inc.
ClinicalTrials.gov Identifier: NCT01221441     History of Changes
Other Study ID Numbers: TGC09201
First Submitted: October 13, 2010
First Posted: October 15, 2010
Results First Submitted: November 5, 2015
Results First Posted: February 15, 2016
Last Update Posted: February 15, 2016