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

Phase 1
Completed
Conditions
Degenerative Arthritis
Interventions
Biological: TissueGene-C(Low dose)
Biological: TissueGene-C(High dose)
Biological: TissueGene-C(Medium dose)
Registration Number
NCT02341391
Lead Sponsor
Kolon Life Science
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TissueGene-C(Low dose)TissueGene-C(Low dose)Single intra-articular injection to the damaged knee joint at doses of 3.0 x 10\^6 cells
TissueGene-C(High dose)TissueGene-C(High dose)Single intra-articular injection to the damaged knee joint at doses of 3.0 x 10\^7 cells
TissueGene-C(Medium dose)TissueGene-C(Medium dose)Single intra-articular injection to the damaged knee joint at doses of 1.0 x 10\^7 cells
Primary Outcome Measures
NameTimeMethod
Number of Participants with Adverse Events after the administration of TissueGene-C6 months

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

Secondary Outcome Measures
NameTimeMethod
Changes in 100 mm-VASbefore 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)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)

Changes in MRI scanbefore 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 resultsbefore and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months

Comparative Evaluation of knee exam

Replication-competent retrovirus test (RCR test)before and 7 days, 14 days, 21 days, 28 days, 3 months, and 6 months

Replication-competent retrovirus test (RCR test)

Changes in WOMAC scoresbefore 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)

Trial Locations

Locations (1)

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

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