Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis

Phase 2

Completed

• Conditions: Degenerative Arthritis
• Interventions: Biological: TissueGene-C(Low dose); Biological: TissueGene-C(High dose)

• Registration Number: NCT02341378
• Lead Sponsor: Kolon Life Science

Brief Summary

To assess the efficacy and safety of the intra-articular injection of TissueGene-C in patients with degenerative arthritis of the knee

Detailed Description

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

During the clinical trial Phase 2A, we compare low dose or high dose TissueGene-C in 6 months trial with 28 outpatients who have degenerative arthritis. The patients are randomized to two dose levels of TisssueGene-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 Timeline

• Study Start: 2009-08
• Primary Completion: 2010-06
• Study Completion: 2010-10
• Status Verified: 2015-01
• Study First Submitted: 2015-01-08
• Study First Submitted QC: 2015-01-13
• Study First Posted: 2015-01-19
• Last Update Submitted: 2015-01-21
• Last Update Posted: 2015-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

1. Male or female, aged 45 years or more
2. With grade 4 degenerative arthritis of the knee [based on the International Cartilage Repair Society(ICRS) evaluation criteria from the MRI results]
3. With less than 6 cm2major lesions
4. With major lesions (grade 4) concentrated in only one section of the knee and considered the main cause of the clinical symptoms
5. Unresponsive to conventional symptomatic treatment
6. Healthy and with no major physical examination, hematology, serum chemistry, and urine test findings and no significant medical history
7. Agreed to use an effective contraceptive method during the study period
8. Voluntarily agreed to participate in this study and signed the Informed Consent Form

Exclusion Criteria

1. Abnormal screening laboratory test (hematology, serum, and urine test) findings

2. Took anti-inflammatory medications (prescribed or over-the-counter), including natural medicines, within 14 days before the injection of the investigational product

3. Took antirheumatic drugs (e.g., methotrexate or antimetabolites) within three months before enrollment in this study

4. Has a history of drug abuse within one year from the enrolment, or has positive results in the urine drug test or serum alcohol test at the screening visit

5. Received an injection in the target knee within two months before enrollment in this study

6. Pregnant or breastfeeding female

7. 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, and synovial chondromas)

8. With a current infectious disease, including HIV or hepatitis

9. Has 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

10. Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study

11. Considered by the investigator inappropriate for participation in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TissueGene-C (Low dose)	TissueGene-C(Low dose)	Single intra-articular injection to the damaged knee joint at a dose of 6.0 x 10\^6 cells
TissueGene-C (High dose)	TissueGene-C(High dose)	Single intra-articular injection to the damaged knee joint at a dose of 1.8 x 10\^7 cells

Primary Outcome Measures

Name	Time	Method
Changes in IKDC Subjective Knee Evaluation	Week 0, 12 and 24	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events	Week 0, 2, 4, 12 and 24	Allergic reaction, Injection site reaction , Infection in the injection site, Fibrosis, Fibrosis-deep connective tissue, Muscular/skeletal hypoplasia, TGF-β1 Enzyme-linked Immunosorbent Assay (ELISA) result, Polymerase Chain Reaction(PCR) for the vector DNA test results
Evaluation of Physical examination and laboratory tests	Week 0, 2, 4, 12 and 24	Vital signs, Physical examination findings, Monitoring of the hematology, serum chemistry, and urine test results
Changes in 100 mm-VAS	Week 0, 12 and 24	Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)
Comparative Evaluation of Knee MRI	Week 0, 12 and 24	Change in the Magnetic Resonance Images (MRI) scan results after the administration of TissueGene-C
Changes in WOMAC scores	Week 0, 12 and 24	Pain, stiffness, and physical function of the knee will be measured by the Western Ontario and McMaster Universities(WOMAC)

Trial Locations

Locations (3)

Seoul National Univ. Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Gangnam-gu, Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of