Efficacy and Safety Study of TissueGene-C Mixed With Fibrin-glue for the Patients With Degenerative Arthritis

A Single-blind, Randomized, Parallel-group, Multi-center Phase 2 Study to Determine the Efficacy and Safety of TissueGene-C Mixed With Fibrin-glue in Patients With Degenerative Arthritis

The purpose of this study is to determine whether TissueGene-C, allogeneic human chondrocytes expressing Transforming Growth Factor(TGF)-b1, mixed with fibrin-glue is effective and safe in patients with degenerative arthritis.

Study Overview

• Status: Completed
• Conditions: Degenerative Arthritis
• Intervention / Treatment: Biological: TissueGene-C (Low dose); Biological: TissueGene-C (High dose)

Detailed Description

TissueGene-C is a biological new drug which consists of non-transduced chondrocytes and transduced chondrocytes that express TGF-b1 to regenerate the damaged cartilage.

During the clinical trial Phase 2, the investigators compare low dose or high dose TissueGene-C in 12 - months trial with 18 outpatients who have degenerative arthritis. The patients are randomized to two dose levels of TissueGene-C by 1:1 ratio, and they are monitored and recorded for alleviating symptoms, sports activities, function of the knee, and the presence of adverse events.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Kyungpook National University Hospital
  • Incheon, Korea, Republic of, 400-711
    • Inha University Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 158-710
    • Ewha Womans University Mokdong Hospital

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. Female or male aged 18 years or more
2. Diagnosed with degenerative arthritis of the knee
3. With an IKDC score of 60 or lower at the screening visit
4. With a BMI of higher than18.5 and lower than 30
5. With an International Cartilage Repair Society(ICRS) Grade IV cartilage damage in the major lesions, as confirmed through an MRI scan
6. With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms
7. With major lesions defect size 2 cm2 ~ 10cm2
8. With no alleviation of the symptoms even after at least three months of non-surgical treatment
9. Healthy, with no major findings from the physical examination, hematology, serum chemistry, and urine tests, and no significant medical history
10. Agreed to use an effective contraceptive method during the study period
11. Voluntarily agreed to participate in this study, and signed the informed consent form

Exclusion Criteria:

1. Showed clinically significant hematology, serum chemistry, and urine test results at the screening visit
2. Mechanical axis (HKA) is greater than 5°
3. Patients receiving injections to the treated knee within 2 months prior to study entry
4. Patients who are pregnant or currently breast-feeding children
5. With another joint disease (e.g., inflammatory arthritis, infectious arthritis)
6. With an infectious disease, including HIV or hepatitis

7. With any of the following clinically significant diseases:

   • heart disease [e.g., myocardial infarction, arrhythmia, other serious heart diseases,
   • kidney disease (e.g., chronic renal failure, glomerulonephritis)
   • liver disease (e.g., liver cirrhosis, fatty liver, acute or chronic liver disease)
   • endocrine disease (e.g., hyperthyroidism, hypothyroidism, thyroiditis, diabetes insipidus, Cushing's disease)
   • insulin-dependent diabetes mellitus
   • medical history of past or current malignant tumor

   • In particular, the tumors that TissueGene-C may aggravate can be screened using the following tests:

     • Leukemia (White Blood Cell level in the hematology)
     • Osteochondroma, Chondromas, Chondroblastoma, Chondromyxoid fibroma, Chondrosarcoma(Alkaline phosphatase level in the hematology)
8. Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study
9. Considered inappropriate by the investigator for participation in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TissueGene-C (Low dose); TissueGene-C (1.0 x 10^6 cells per cm^2 of the cartilage defect) combined with fibrin-glue	Biological: TissueGene-C (Low dose); TissueGene-C at 1.0 x 10^6 cells mixed with fibrin-glue
EXPERIMENTAL: Experimental: TissueGene-C (High dose); TissueGene-C (3.0 x 10^6 cells per cm^2 of the cartilage defect) combined with fibrin-glue	Biological: TissueGene-C (High dose); TissueGene-C at 3.0 x 10^6 cells mixed with fibrin-glue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in IKDC Subjective Knee Evaluation	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)	Week 0 and 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in WOMAC scores	Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities (WOMAC)	Week 0, 24 and 48
Changes in KOOS scores	Symptoms, pain and functionality of the knee joint will be evaluated via the Knee Injury and Osteoarthritis Outcome Score (KOOS)	Week 0, 24 and 48
Changes in 100 mm-VAS	Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)	Week 0, 24 and 48
Comparative Evaluation of Knee Magnetic Resonance Images (MRIs)	Comparison of pre-procedure MRI scans to those obtained at pre-dosing and at months 6 and 12 by an independent radiographic reviewer	Week 0, 24 and 48
Changes in ICRS Cartilage Repair Assessment		week 0 and 48
Changes in IKDC Subjective Knee Evaluation	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)	Week 0 and 24
Changes in KOOS QOL Sub-scale scores		Week 0, 24 and 48
Proportion of Patients Use of Rescue Medication		Week 12, 24 and 48

Collaborators and Investigators

• Sponsor: Kolon Life Science
• Investigators: Principal Investigator: Myung chul Lee, MD, PhD, Seoul National University Hospital; Principal Investigator: Seong Il Bin, MD, PhD, Asan Medical Center; Principal Investigator: Myung Gu Kim, MD, PhD, Inha University Hospital; Principal Investigator: Jae Doo Yoo, MD, PhD, Ewha Womans University Mokdong Hospital; Principal Investigator: Hee Su Kyung, MD, PhD, Kyungpook National University Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): April 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: April 3, 2013
• First Submitted That Met QC Criteria: April 5, 2013
• First Posted (ESTIMATE): April 8, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): January 22, 2015
• Last Update Submitted That Met QC Criteria: January 20, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Osteoarthritis; Degenerative Arthritis; Cell mediated gene therapy; Fibrin-glue
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: KS-TGC(S)-01-2