Safety Study of TissueGene-C in Degenerative Joint Disease of the Knee

Study Overview
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Brief Summary
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The study is being conducted to investigate the safety and activity of TissueGene-C injected into the knee joint of patients with chronic degenerative joint disease (DJD) who will be undergoing total knee replacement.

Detailed Description
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The purpose of this first human study is to investigate the safety and biological activity of intra-articularly applied TissueGene-C in patients with chronic degenerative joint disease (DJD) who will be undergoing total knee replacement. In addition, data on joint pain, range of motion, and functionality will be obtained in this patient population prior to total knee replacement. The primary objective of this study is to evaluate the safety and biological activity of intra-articularly administered TissueGene-C as evidenced by observation of the injection site for irritation or other abnormalities affecting the incidence and severity of adverse events, and the changes in physical examination findings and laboratory tests as compared to the placebo control. The secondary objectives of this study are to: Evaluate the dose response of the hChonJb#7 cells in grafting at the defect as compared to the placebo control. Evaluate distribution of hChonJb#7 cells out of the injection site. Evaluate the regeneration of hyaline cartilage as determined by the histological analysis of the resected knee tissue. Evaluate the joint for evidence of tissue overgrowth or transformation. Evaluate the biological activity of TissueGene-C on joint pain, range of motion and functionality as compared to the placebo control

Official Title
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A Phase 1 Study to Determine the Safety and Biological Activity of Cell-Mediated Gene Therapy Using TissueGene-C in Patients With Degenerative Joint Disease Prior to Total Knee Arthroplasty

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Biological: TissueGene-C
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female subjects Age 18 years and older 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 Degenerative Joint Disease (DJD) of the knee that is refractory to existing drug therapies and who are scheduled for Total Knee Arthroplasty. Based on Radiographic findings, defect should be more than 2 cm. Patients providing written informed consent, after the nature of the study, are fully explained. 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 (SBP) should be between 90-160mm. Hg, and Diastolic Blood Pressure (DBP) between 50-90mm.Hg, Osteoarthritis confirmed by the Radiographic Criteria of Kellgren and Lawrence Symptom of pain for more than four (4) consecutive months and intensity greater than Grade 4 on the 11-point numeric scale. Exclusion Criteria: Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results Patients taking anti-inflammatory medications (prescription or over-the-counter), including herbal therapies, within 14 days of baseline visit Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug/alcohol test at the time of screening Patients receiving injections to the treated knee within 2 months prior to study entry 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, and synovial chondromatosis. Patients with ongoing infectious disease, including HIV and hepatitis 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. Positive drug screen at screening visit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>TissueGene-C single intraarticular injection of 3x10e6 cells/joint | Biological: TissueGene-C<br>* TissueGene-C at 3x10e6, 1x10e7 or 3x10e7 cells/joint to be administered by intra-articular injection<br>|
| Experimental: 2<br>TissueGene-C single intraarticular injection of 1x10e7 cells/joint | Biological: TissueGene-C<br>* TissueGene-C at 3x10e6, 1x10e7 or 3x10e7 cells/joint to be administered by intra-articular injection<br>|
| Experimental: 3<br>TissueGene-C single intraarticular injection of 3x10e7 cells/joint | Biological: TissueGene-C<br>* TissueGene-C at 3x10e6, 1x10e7 or 3x10e7 cells/joint to be administered by intra-articular injection<br>|
| Placebo Comparator: 4<br>Placebo control single intraarticular injection | Biological: Placebo<br>* Placebo control (DMEM)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Adverse Events | The incidence of observations at the site of administration and the incidence adverse events assessed through 28 days after treatment. | Through 28 days post-dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Showing Engraftment at the Defect | Dose Response of the TG-C in Engrafting at the Defect as Compared to Placebo Control | 28 Days | 
| Number of Patients With Distribution of hChonJb#7 Cells Detected Outside of the Injection Site | Number of Patients with Distribution of hChonJb#7 Cells Detected Outside of the Injection Site as determined by PCR analysis for vector DNA. | 12 Months | 
| Number of Participants With Observable Evidence of Cartilage Regeneration | The evaluation of regeneration of hyaline cartilage as determined by histological analysis of resected knee tissue and observation for engraftment and cartilage production. | Days 0, 3, 7, 11, 28 (prior to surgery), and day 29 (one day post-surgery) following dosing. Follow-up patient monitoring will be performed at 3, 6, 9, and 12 months following dosing | 
| Number of Patients With Tissue Overgrowth or Transformation in the Knee Joint | Visual and histological analysis of knee joint tissues to determine the number of patients with tissue overgrowth or transformation | 29 | 
| Number of Patients With Improvements in Pain and Function of the Knee Joint | Assessment of the number of patients with improvement in pain and function of the knee joint | 28 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, knee