Safety and Biological Efficacy Study of TisssueGene-C to Degenerative Arthritis

A Dose-escalating, Single-center, Phase I Clinical Trial to Investigate the Safety and Biological Efficacy of TissueGene-C in Degenerative Arthritis Patients.

The primary purpose of the this study is to evaluate the safety of TissueGene-C, a gene therapy product that uses allogenic human chondrocytes expressing Transforming Growth Factor(TGF)-β1 by assessing the inflammation at the injection site, the incidence and severity of the adverse events, the physical examination findings, and the laboratory test results after the intra-articular injection of TissueGene-C.

And Secondary purpose is to evaluate the biological efficacy (knee pain, range of motion, functional tests, and MRI) of TissueGene-C and the distribution of TissueGene-C outside the injection site.

Study Overview

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

Detailed Description

TissueGene-C is a biological new drug which consists of normal chondrocyte cells and transduced chondrocyte cells that express growth factor to modify osteoarthritis symptom for long term period.

During clinical trial Phase 1, we compare three different dose levels of TisssueGene-C in 6 months with 12 outpatients with degenerative arthritis. The patients are randomized by three different dose levels of TisssueGene-C in 1:1:1 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): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients
2. Patients aged 45 years or more with Grade IV [based on the International Cartilage Repair Society(ICRS) evaluation criteria from the MRI scan results] degenerative arthritis of the knee, whose symptoms had not been relieved by the conventional symptomatic treatment
3. Healthy, with no major physical examination, hematology, serum chemistry, and urine test findings and no significant medical history
4. Patients with cartilage damage sized 2-6 cm2 (based on the ICRS evaluation criteria from the MRI scan results)
5. Voluntarily agreed to participate in this study and signed the informed consent form

Exclusion Criteria:

1. Showed clinically significant hematology, serum chemistry, or urine test results at the screening visit
2. Took an anti-inflammatory medication (prescribed or over-the-counter), including natural medicine, within 14 days from the administration of the investigational product
3. Has a history of drug abuse within one year from the enrollment, or the urine test or blood alcohol test result was positive at the screening visit
4. Received any injection in the target knee within two months before the initiation of the study
5. Pregnant or breastfeeding female
6. 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 the tibia, ochronosis, hemophilic arthropathy, infectious arthritis, Charcot's disease in the knee joint, villonodular synovitis, and synovial chondromas)
7. With an infectious disease, including HIV or hepatitis (HBV/HCV)

8. With a history any of the following clinically significant diseases:

   • heart disease [e.g., myocardial infarction, arrhythmia, other serious heart disease, 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 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
9. Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study
10. Showed positive drug test results at the screening visit
11. Did not agree to use a contraceptive method (male and female)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TissueGene-C(Low dose); Single intra-articular injection to the damaged knee joint at doses of 3.0 x 10^6 cells	Biological: TissueGene-C(Low dose); 3.0 x 10^6 cells
Experimental: TissueGene-C(Medium dose); Single intra-articular injection to the damaged knee joint at doses of 1.0 x 10^7 cells	Biological: TissueGene-C(Medium dose); 1.0 x 10^7 cells
Experimental: TissueGene-C(High dose); Single intra-articular injection to the damaged knee joint at doses of 3.0 x 10^7 cells	Biological: TissueGene-C(High dose); 3.0 x 10^7 cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events after the administration of TissueGene-C	Number of Participants with Adverse Events after the administration of TissueGene-C	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in MRI scan	Change in the MRI scan results after the administration of TissueGene-C	before and 28 days, 3 months, and 6 months
Change in the Knee Society Clinical Rating System(KSCRS) test results	Comparative Evaluation of knee exam	before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months
Changes in WOMAC scores	Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities(WOMAC)	before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months
Changes in 100 mm-VAS	Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)	before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months
Analysis of the TGF-β1 expression using Enzyme-linked Immunosorbent Assay(ELISA) and Polymerase Chain Reaction(PCR)	Analysis of the TGF-β1 expression using Enzyme-linked Immunosorbent Assay(ELISA) and Polymerase Chain Reaction(PCR)	before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months
Replication-competent retrovirus test (RCR test)	Replication-competent retrovirus test (RCR test)	before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months

Collaborators and Investigators

• Sponsor: Kolon Life Science

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: January 8, 2015
• First Submitted That Met QC Criteria: January 16, 2015
• First Posted (Estimate): January 19, 2015

Study Record Updates

• Last Update Posted (Actual): July 5, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Osteoarthritis; chondrocyte cells; gene therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: TGC-KI-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No