Study of TG-C in Patients With Grade 3 Degenerative Joint Disease of the Knee

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

The purpose of this study is to see if we can safely regenerate cartilage without invasive surgery using a biologic product called TissueGene-C.

Study Overview

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

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:

1. Evaluate the efficacy of TissueGene-C with regard to knee functionality and symptoms of knee osteoarthritis including pain.
2. 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.
3. Evaluate the incidence and dose of analgesia and/or anti-inflammatory medication.
4. Evaluate the regeneration of hyaline cartilage as determined by 3T magnetic resonance imaging (MRI).
5. Evaluate distribution of hChonJb#7 cells out of the injection site.
6. Evaluate the efficacy of TissueGene-C by evaluating the need for total knee arthroplasty after treatment

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Pinellas Park, Florida, United States, 33781
      • Advent Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Rothman Institute
    • State College, Pennsylvania, United States, 16801
      • University Orthopedics
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Commonwealth Orthopedics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or Female subject
2. Age 18 to 70 years

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.

   1. Body Mass Index (BMI) should be between '18.5 - 45.5'. The applied scale is the same for both men and women.
   2. Blood Pressure measurements - Systolic Blood Pressure should be between 90-160mm. Hg, and Diastolic Blood Pressure between 50-90mm.Hg,
4. Patients with Grade 3 chronic osteoarthritis of the knee as determined by the Radiographic Criteria of Kellgren and Lawrence.
5. Symptom of pain for more than four (4) consecutive months and intensity of ≥ 40 and ≤ 90 on the 100-mm scale.
6. Patients should be cleared to use protocol specified equipment: 3T MRI.
7. Patients providing written informed consent after the nature of the study is fully explained and understood by the patient.

Exclusion Criteria:

1. Age 71 or older
2. Patients with abnormal hematology, serum chemistry, or urinalysis screening laboratory results.
3. Patients taking non-steroidal anti-inflammatory medications within 14 days of baseline visit unless washed out as per section 3.6.4 above.
4. Patients taking steroidal anti-inflammatory medications within 2 months of baseline visit.
5. Patients with a recent (within 1 year) history of drug abuse and/or a positive urine drug test at the time of screening.
6. Patients receiving injections to the treated knee within 2 months prior to study entry
7. Patients who are contraindicated for 3T MRI.
8. Patients who are pregnant or currently breast-feeding children.
9. 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.
10. Patients with ongoing infectious disease, including HIV and hepatitis B or C.
11. Patients with clinically significant cardiovascular, renal, hepatic, endocrine disease, cancer, or Type I diabetes.
12. Patients participating in a study of an experimental drug or medical device within 30 days of study entry.
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TissueGene-C; TissueGene-C at 3 x 10e7 cells per injection (intraarticular)	Biological: TissueGene-C; Single intraarticular injection at 3 x 10e7 cells; Other Names: TG-C
PLACEBO_COMPARATOR: Placebo Control; Normal Saline injection	Drug: Normal Saline; Single intraarticular injection of normal saline as a placebo control; Other Names: 0.9% Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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
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

Collaborators and Investigators

• Sponsor: Kolon TissueGene, Inc.
• Investigators: Principal Investigator: David W Romness, MD, Commonwealth Orthopedics, Virginia Hospital Center

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: October 13, 2010
• First Submitted That Met QC Criteria: October 13, 2010
• First Posted (ESTIMATE): October 15, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): February 15, 2016
• Last Update Submitted That Met QC Criteria: January 19, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Osteoarthritis; Knee; Cartilage
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Joint Diseases
• Other Study ID Numbers: TGC09201