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The purpose of this study is to see if we can safely regenerate cartilage without invasive surgery using a biologic product called TissueGene-C.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TissueGene-C | Experimental | TissueGene-C at 3 x 10e7 cells per injection (intraarticular) |
|
| Placebo Control | Placebo Comparator | Normal Saline injection |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TissueGene-C | Biological | Single intraarticular injection at 3 x 10e7 cells |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 1 Year |
| 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. | 1 Year |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 2 Years |
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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.
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:
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| Name | Affiliation | Role |
|---|---|---|
| Michael A Mont, MD | Sinai Hospital of Baltimore | Principal Investigator |
| David W Romness, MD | Commonwealth Orthopedics, Virginia Hospital Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Advent Clinical Research | Pinellas Park | Florida | 33781 | United States | ||
| Sinai Hospital of Baltimore |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29145839 | Derived | 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. | |
| 26188189 | Derived |
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| ID | Title | Description |
|---|---|---|
| FG000 | TissueGene-C | TissueGene-C at 3 x 10e7 cells per injection (intraarticular) TissueGene-C: Single intraarticular injection at 3 x 10e7 cells |
| FG001 | Placebo Control | Normal Saline injection Normal Saline: Single intraarticular injection of normal saline as a placebo control |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | TissueGene-C | TissueGene-C at 3 x 10e7 cells per injection (intraarticular) TissueGene-C: Single intraarticular injection at 3 x 10e7 cells |
| BG001 | Placebo Control | Normal Saline injection Normal Saline: Single intraarticular injection of normal saline as a placebo control |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Patients with available baseline IKDC scores | Posted | Least Squares Mean | 95% Confidence Interval | scores on a scale | 1 Year |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TissueGene-C | TissueGene-C at 3 x 10e7 cells per injection (intraarticular) TissueGene-C: Single intraarticular injection at 3 x 10e7 cells |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sciatica | Nervous system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| R. Ogden Copeland | TissueGene, Inc | (301) 921-6000 | 122 | ocopeland@tissuegene.com |
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| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010003 | Osteoarthritis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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| Normal Saline | Drug | Single intraarticular injection of normal saline as a placebo control |
|
|
| 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. |
| 2 Years |
| 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) | 1 Year |
| 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) | 2 Years |
| 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 | 2 Years |
| 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) | 2 Years |
| The Incidence of Total Knee Arthroplasty | Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C | 2 Years |
| 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 | 2 Years |
| 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 | 2 Years |
| 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 | 2 Years |
| 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) | 2 Years |
| Baltimore |
| Maryland |
| 21215 |
| United States |
| Rothman Institute | Philadelphia | Pennsylvania | 19107 | United States |
| University Orthopedics | State College | Pennsylvania | 16801 | United States |
| Commonwealth Orthopedics | Arlington | Virginia | 22205 | United States |
| 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
Normal Saline injection
Normal Saline: Single intraarticular injection of normal saline as a placebo control
|
|
|
| Primary | 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. | Patients with available baseline and 1 year VAS score | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | 1 Year |
|
|
|
|
| Secondary | 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. | Posted | Least Squares Mean | 95% Confidence Interval | scores on a scale | 2 Years |
|
|
|
|
| Secondary | 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. | Posted | Least Squares Mean | 95% Confidence Interval | scores on a scale | 2 Years |
|
|
|
|
| Secondary | 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) | Patients with available baseline and 1-year MRIs | Posted | Least Squares Mean | 95% Confidence Interval | scores on a scale | 1 Year |
|
|
|
| Secondary | 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) | Patients that completed 2 year follow-up | Posted | Mean | Standard Deviation | scores on a scale | 2 Years |
|
|
|
| Secondary | 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 | Patients taking at least one analgesia medication | Posted | Number | participants | 2 Years |
|
|
|
| Secondary | 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) | Patients that completed 2-year follow-up | Posted | Least Squares Mean | 95% Confidence Interval | scores on a scale | 2 Years |
|
|
|
| Secondary | The Incidence of Total Knee Arthroplasty | Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C | All patients that participated in the study | Posted | Number | participants | 2 Years |
|
|
|
| Secondary | 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 | All participants receiving placebo or active treatment | Posted | Number | participants | 2 Years |
|
|
|
| Secondary | 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 | All patients receiving treatment with either active or placebo | Posted | Number | participants | 2 Years |
|
|
|
| Secondary | 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 | All patients | Posted | Number | participants | 2 Years |
|
|
|
| Secondary | 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) | Patients with completed SF-36 questionnaire at 104 weeks | Posted | Least Squares Mean | 95% Confidence Interval | scores on a scale | 2 Years |
|
|
|
| 7 |
| 67 |
| 45 |
| 67 |
| EG001 | Placebo Control | Normal Saline injection Normal Saline: Single intraarticular injection of normal saline as a placebo control | 4 | 35 | 8 | 35 |
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Radius Fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Total Knee Arthroplasty | Surgical and medical procedures | Systematic Assessment |
|
| Hiatal hernia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | Systematic Assessment |
|
| Invertebral Disc Protrusion | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Microdiscectomy | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Prostatectomy | Surgical and medical procedures | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Spinal Column Stenosis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Spinal Fusion Surgery | Surgical and medical procedures | Systematic Assessment |
|
| Spinal Laminectomy | Surgical and medical procedures | Systematic Assessment |
|
| Invertebral Disc Operation | Surgical and medical procedures | Systematic Assessment |
|
| Lumbar Degenerative Disc Disease | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | Systematic Assessment |
|
| Chills | General disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Feeling Cold | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| C-reactive Protein Increased | Investigations | Systematic Assessment |
|
| Eosinophil Count Increased | Investigations | Systematic Assessment |
|
| Interleukin Level Increased | Investigations | Systematic Assessment |
|
| Red Blood Cell Sedimentation Increased | Investigations | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Arthropathy | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Joint Effusions | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Muscular Weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain in Extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Weight Bearing Difficulty | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Presyncope | Nervous system disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hair Growth Abnormal | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Skin Warm | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Increased White Blood Cells/Neutrophils | Investigations | Systematic Assessment |
|
| Right Knee Swelling | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Asthenia | General disorders | Systematic Assessment |
|
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| Severe |
|