Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis

A Placebo Controlled, Single-blind, Randomized, Multi-center Phase 2B Study to Determine the Efficacy and Safety of TissueGene-C, an Allogeneic Human Chondrocytes Expressing TGF-b1, in Patients With Degenerative Arthritis

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

Study Overview

• Status: Completed
• Conditions: Degenerative Arthritis
• Intervention / Treatment: Biological: TissueGene-C; Drug: Normal Saline

Detailed Description

TissueGene-C is a biological new drug which consists of normal chondrocytes and transduced chondrocytes that express growth factors to regenerate the damaged cartilage tissues.

In the clinical trial Phase 2b, the investigators compared TissueGene-C to placebo during 6 - months trial with 54 outpatients who have had degenerative arthritis. The outpatients are assigned to TissueGene-C or placebo in 1:1 ratio, and will be monitored and recorded for improving clinical symptoms, sports activities, and function of the knee, and for the presence of adverse events.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National Univ. Hospital
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of, 135-710
      • Samsung Medical Center

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 Grade 2 or 3 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence
5. With a Body Mass Index(BMI) of higher than18.5 and lower than 30
6. With an International Cartilage Repair Society(ICRS) Grade IV cartilage damage in the major lesions, as confirmed through an MRI scan
7. With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms
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. Falls under Inclusion Criteria 6 but with the damage in the relevant lesion considered ICRS Grade IV sized more than 6 cm2
3. Took glucosamine, chondroitin, or any natural medicine within 14 days before the injection of the investigational product (but if the 14-day washout period had elapsed, the patient can be enrolled in this study)
4. Has taken anti-inflammatory drugs (prescribed or over-the-counter) within 14 days before the injection of the investigational product (but if the 14-day washout period had elapsed, the patient can be enrolled in this study)
5. Has taken immunosuppressive agents, including antirheumatic drugs (e.g., methotrexate or antimetabolites) within 3 months before enrollment in this study
6. With a history of drug abuse within one year prior to enrollment in this study, or showed positive results in the urine drug test or the serum alcohol test at the screening visit
7. Received an injection in the target knee within two months before enrollment in this study
8. Pregnant or breastfeeding female
9. With another joint disease apart from degenerative arthritis (e.g., systemic rheumatic inflammatory disease associated with the knee or chondrocalcinosis, hemachromatosis, inflammatory arthritis, necrosis of the trochanter, Paget's disease adjacent to a joint in the femur or tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's disease in the knee joint, villonodular synovitis, synovial chondromas)
10. With an infectious disease, including HIV or hepatitis

11. With any of the following clinically significant diseases:

    • heart disease [e.g., myocardial infarction, arrhythmia, other serious heart diseases, coronary artery bypass graft (CABG)]
    • 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)
12. Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study
13. 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; Single intra-articular injection to the damaged knee joint a dose of 1.8 x 10^7 cells	Biological: TissueGene-C; TissueGene-C at 1.8 x 10^7 cells
PLACEBO_COMPARATOR: Normal Saline; Single intra-articular injection to the damaged knee joint at the same volume	Drug: Normal Saline; Sodium chloride 0.9%, 3.5ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in IKDC Subjective Score.	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)	Week 0 and 24

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 and 24
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 and 24
Changes in 100 mm-VAS.	Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)	Week 0 and 24
MRI scan	Comparison of pre-procedure MRI scans to those obtained at pre-dosing and at months 6 and 12 following dosing by an independent radiographic reviewer.	Week 0 and 24
Proportion of Patients Use of Rescue Medication		Week 4, 12 and 24

Collaborators and Investigators

• Sponsor: Kolon Life Science
• Investigators: Principal Investigator: Seong Il Bin, MD, PhD, Asan Medical Center; Principal Investigator: Myung Chul Lee, MD, PhD, Seoul National Univ. Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): January 1, 2013

Study Registration Dates

• First Submitted: August 20, 2012
• First Submitted That Met QC Criteria: August 22, 2012
• First Posted (ESTIMATE): August 23, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 22, 2015
• Last Update Submitted That Met QC Criteria: January 21, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Osteoarthritis; Gene therapy; Chondrocyte cells
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: KS-TGC-01-2B