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

• ClinicalTrials.gov Identifier: NCT02341391
• Recruitment Status: Completed
• First Posted: January 19, 2015
• Last Update Posted: July 5, 2018
• Sponsor: Kolon Life Science
• Information provided by (Responsible Party): Kolon Life Science

Tracking Information

• First Submitted Date: January 8, 2015
• First Posted Date: January 19, 2015
• Last Update Posted Date: July 5, 2018
• Study Start Date: February 2007
• Actual Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 2, 2018)

Number of Participants with Adverse Events after the administration of TissueGene-C [ Time Frame: 6 months ]

Number of Participants with Adverse Events after the administration of TissueGene-C

• Original Primary Outcome Measures (submitted: January 16, 2015): Number of Participants with Adverse Events after the administration of TissueGene-C [ Time Frame: 6 months ]

Current Secondary Outcome Measures (submitted: July 2, 2018)

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

Original Secondary Outcome Measures (submitted: January 16, 2015)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Biological Efficacy Study of TisssueGene-C to Degenerative Arthritis
• Official Title: A Dose-escalating, Single-center, Phase I Clinical Trial to Investigate the Safety and Biological Efficacy of TissueGene-C in Degenerative Arthritis Patients.

Brief Summary

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.

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
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Degenerative Arthritis

Intervention

• Biological: TissueGene-C(Low dose)
  3.0 x 10^6 cells
• Biological: TissueGene-C(Medium dose)
  1.0 x 10^7 cells
• Biological: TissueGene-C(High dose)
  3.0 x 10^7 cells

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 16, 2015): 12
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 2008
• Actual Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT02341391
• Other Study ID Numbers: TGC-KI-01
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kolon Life Science
• Original Responsible Party: Same as current
• Current Study Sponsor: Kolon Life Science
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Chul Won Ha, MD, PhD; Samsung Medical Center

• PRS Account: Kolon Life Science
• Verification Date: July 2018