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

• 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: Kolon TissueGene, Inc.
• Information provided by (Responsible Party): Kolon TissueGene, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee	Biological: TissueGene-C; Drug: Normal Saline	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: May 2011
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: October 2014

Arms and Interventions

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 Name: TG-C
Placebo Comparator: Placebo Control; Normal Saline injection	Drug: Normal Saline; Single intraarticular injection of normal saline as a placebo control; Other Name: 0.9% Saline

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Score at 1 Year [ Time Frame: 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.
2. Change From Baseline in Visual Analog Scale (VAS) Score at 1 Year [ Time Frame: 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.

Secondary Outcome Measures :

1. Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 Years [ Time Frame: 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. Change From Baseline in Articular Cartilage Damage in the Knee as Determined by the Lysholm Knee Score at 2 Years [ Time Frame: 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.
3. Comparative Evaluation of Knee Magnetic Resonance Images (MRIs) From Baseline to 1 Year [ Time Frame: 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)
4. Change in Pain Severity From Baseline to 2 Years as Assessed by Questionnaire [ Time Frame: 2 Years ]
   Change in pain severity (on a scale from 1 to 4) from baseline to 2 years as measured by a questionnaire (lower scores better)
5. Number of Participants With Change in Pain Severity Measured by Incidence and Dose of Analgesia [ Time Frame: 2 Years ]
   The number of participants that had a change in pain severity as measured by the incidence and dose of analgesic medications
6. Change From Baseline in Knee Function as Determined by the Lower Extremity Functional Scale at 2 Years [ Time Frame: 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)
7. The Incidence of Total Knee Arthroplasty [ Time Frame: 2 Years ]
   Quantification of the incidence of total knee arthroplasty of the treated knee subsequent to treatment with TissueGene-C
8. The Number of Patients Experiencing Injection Site Reactions Related to Treatment [ Time Frame: 2 Years ]
   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
9. The Incidence and Severity of Adverse Events in Treated Patients [ Time Frame: 2 Years ]
   The incidence and severity of adverse events assessed through 104 weeks (2 years) after dose administration
10. Number of Participants With Adverse Events Due to Clinically Significant Changes in Hematology and Urinalysis Tests [ Time Frame: 2 Years ]
    The number of participants with changes in clinical hematology, chemistry, and urinalysis test results through 2 years that were considered Adverse Events
11. Change in SF-36 General Health Assessment Questionnaire (Overall Score) From Baseline to 2 Years [ Time Frame: 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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Advent Clinical Research

Pinellas Park, Florida, United States, 33781

United States, Maryland

Sinai Hospital of Baltimore

Baltimore, Maryland, United States, 21215

United States, Pennsylvania

Rothman Institute

Philadelphia, Pennsylvania, United States, 19107

University Orthopedics

State College, Pennsylvania, United States, 16801

United States, Virginia

Commonwealth Orthopedics

Arlington, Virginia, United States, 22205

Sponsors and Collaborators

Kolon TissueGene, Inc.

Investigators

• Principal Investigator: Michael A Mont, MD; Sinai Hospital of Baltimore
• Principal Investigator: David W Romness, MD; Commonwealth Orthopedics, Virginia Hospital Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Kolon TissueGene, Inc.
• ClinicalTrials.gov Identifier: NCT01221441
• Other Study ID Numbers: TGC09201
• First Posted: October 15, 2010
• Results First Posted: February 15, 2016
• Last Update Posted: February 15, 2016
• Last Verified: January 2016

Keywords provided by Kolon TissueGene, Inc.:

Cartilage; Knee; Osteoarthritis

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Joint Diseases; Arthritis; Musculoskeletal Diseases; Rheumatic Diseases