Safety Study of TissueGene-C in Degenerative Joint Disease of the Knee (TGC-03-01)

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Biological: TissueGene-C; Biological: Placebo

Detailed Description

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:

1. Evaluate the dose response of the hChonJb#7 cells in grafting at the defect as compared to the placebo control.
2. Evaluate distribution of hChonJb#7 cells out of the injection site.
3. Evaluate the regeneration of hyaline cartilage as determined by the histological analysis of the resected knee tissue.
4. Evaluate the joint for evidence of tissue overgrowth or transformation.
5. Evaluate the biological activity of TissueGene-C on joint pain, range of motion and functionality as compared to the placebo control

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Commonwealth Orthopedics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or Female subjects
2. Age 18 years and older
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.
4. Patients with Degenerative Joint Disease (DJD) of the knee that is refractory to existing drug therapies and who are scheduled for Total Knee Arthroplasty.
5. Based on Radiographic findings, defect should be more than 2 cm.
6. Patients providing written informed consent, after the nature of the study, are fully explained.
7. Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the same for both men and women.
8. Blood Pressure measurements - Systolic Blood Pressure (SBP) should be between 90-160mm. Hg, and Diastolic Blood Pressure (DBP) between 50-90mm.Hg,
9. Osteoarthritis confirmed by the Radiographic Criteria of Kellgren and Lawrence
10. Symptom of pain for more than four (4) consecutive months and intensity greater than Grade 4 on the 11-point numeric scale.

Exclusion Criteria:

1. Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results
2. Patients taking anti-inflammatory medications (prescription or over-the-counter), including herbal therapies, within 14 days of baseline visit
3. Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug/alcohol test at the time of screening
4. Patients receiving injections to the treated knee within 2 months prior to study entry
5. Patients who are pregnant or currently breast-feeding children
6. 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.
7. Patients with ongoing infectious disease, including HIV and hepatitis
8. Patients with clinically significant cardiovascular, renal, hepatic, endocrine disease, cancer, or Type I diabetes
9. Patients participating in a study of an experimental drug or medical device within 30 days of study entry.
10. Positive drug screen at screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kolon TissueGene, Inc.
• Investigators: Principal Investigator: Michael Mont, MD, Sinai Hospital of Baltimore; Principal Investigator: David Romness, MD, Commonwealth Orthopedics, Virginia Hospital Center

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: January 11, 2008
• First Submitted That Met QC Criteria: January 22, 2008
• First Posted (Estimate): January 23, 2008

Study Record Updates

• Last Update Posted (Actual): July 7, 2017
• Last Update Submitted That Met QC Criteria: June 7, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: osteoarthritis, knee
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Joint Diseases
• Other Study ID Numbers: TGC-03-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO