Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis

A Placebo Controlled, Double-blind, Randomized, Parallel-group, Multi-center Phase III Study to Determine the Efficacy and Safety of TissueGene-C 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: Placebo

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 the Phase 3 clinical trial , we will compare TissueGene-C to placebo in 26, 52 weeks trial with 156 outpatients who have osteoarthritis. The outpatients are randomized to TissueGene-C or placebo in 1:1 ratio, and they will be monitored and recorded in terms of alleviating symptoms, sports activities, function of the knee, and the presence of adverse events.

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Cheongju, Korea, Republic of, 361-711
    • Chungbuk National University Hospital
  • Daegu, Korea, Republic of, 700-721
    • Kyungpook National Univ. Hospital
  • Incheon, Korea, Republic of, 400-711
    • Inha University Hospital
  • Jeonju, Korea, Republic of, 561-712
    • Chonbuk National University Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of, 110-744
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 137-701
    • The Catholic University of Korea Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 100-032
    • Inje University Seoul Paik Hospital
  • Seoul, Korea, Republic of, 158-710
    • Ewha Womans University Mokdong Hospital
  • Seoul, Korea, Republic of, 133-791
    • Hanyang University Medical Center
  • Ulsan, Korea, Republic of, 682-714
    • Ulsan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients at least 19 years of age
2. Patients diagnosed with degenerative arthritis
3. Patients with IKDC(Knee Documentation Committee subjective score) score of 60 or below
4. Patients with 100 mm VAS(Visual Analog Scale) score of 40 or above
5. With Grade 3 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence
6. With an International Cartilage Repair Society(ICRS) Grade III or IV cartilage damage in the major lesions, as confirmed through an MRI scan
7. With a Body Mass Index(BMI) of higher than18.5 and lower than 30

8. Patients who satisfies the clinical/radiational criteria by the American College of Rheumatology (ACR) guidelines, and applies to one of the following.

   • Older than 50
   • Morning stiffness for less than 30 minutes
   • Crepitus and Osteophytes
9. With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms
10. With no alleviation of the symptoms even after at least three months of non-surgical treatment
11. Healthy, with no major findings from the physical examination, hematology, serum chemistry, and urine tests, and no significant medical history
12. Agreed to use an effective contraceptive method during the study period
13. 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. Regarding inclusion criteria 6. following patients should not be included

   • patients with a major lesion of ICRS grade 4 which is larger than 6cm2(for patient with ICRS grade 4)
   • patients with a major lesion of ICRS grade 3 which is larger than 6cm2(for patient without a ICRS grade 4),
3. Patient who had skin disease around target knee
4. patients who have a positive skin reaction to CS-10
5. Patients who had been administered with drugs such as oriental medicine, glucosamine and chondroitin within 14 days of baseline visit
6. Patients taking steroidal anti-inflammatory medications within 14 days of baseline visit
7. Patients with severe pain in other areas that could effect the diagnosis of the symptoms of the
8. History of surgery like arthroendoscopy within the past 6 months on the target knee
9. Patients who had been administered with immunosuppressants, including antirheumatic drugs (including methotrexate or antimetabolite), within the past 3 months
10. Patients who had been treated with physical therapy or herbal remedy (acupuncture, heat etc.) within 2 weeks of baseline visit
11. History of injection within the past 3 months on the target knee
12. Pregnant or breastfeeding female
13. 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)
14. With an infectious disease, including HIV or hepatitis

15. With any of the following clinically significant diseases:

    • heart disease (e.g., myocardial infarction, arrhythmia, other serious heart diseases, coronary artery bypass graft)
    • 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)
16. Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study
17. Patients who administered the TissueGene-C from past clinical trial
18. 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: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TissueGene-C; Single intra-articular injection to the damaged knee joint at a dose of 1.8 x 10^7 cells	Biological: TissueGene-C; TissueGene-C at 1.8 x 10^7 cells
PLACEBO_COMPARATOR: Placebo; Single intra-articular injection to the damaged knee joint	Drug: Placebo; Placebo control(Normal Saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in IKDC scores	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)	Week 0 and 52
Changes in 100 mm VAS scores	Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)	Week 0 and 52

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)	Wekk 0, 26, 39 and 52
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, 26, 39 and 52
Changes in 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, 26 and 52
Changes in Joint Space Width by an independent radiographic reviewer.		Week 0, 26 and 52
Level of Biomarkers in blood and urine.		Week 0, 26, 39 and 52
Proportion of Patients Use of Rescue Medication.		Week 4, 12, 26, 39 and 52
Changes in IKDC scores	Symptoms, sports activities, and function of the knee will be measured by the International Knee Documentation Committee (IKDC)	Week 0, 26 and 39
Changes in 100 mm VAS scores	Pain of the knee will be measured by the 100mm Visual Analogue Scale (VAS)	Week 0, 26 and 39

Collaborators and Investigators

• Sponsor: Kolon Life Science
• Investigators: Principal Investigator: Seong Il Bin, MD, PhD, Asan Medical Center; Principal Investigator: Myung Gu Kim, MD, PhD, Inha University Hospital; Principal Investigator: Jin Gu Kim, MD, PhD, Inje University; Principal Investigator: Su Hee Kyung, MD, PhD, Kyungpook National University Hospital; Study Chair: Myung Chul Lee, MD, PhD, Seoul National University Hospital; Principal Investigator: Yong In, MD, PhD, The Catholic University of Korea Seoul ST. Mary's Hospita; Principal Investigator: Seong Do Cho, MD, PhD, Ulsan University Hospital; Principal Investigator: Jae Doo Yoo, MD, PhD, Ewha Womans University Mokdong; Principal Investigator: Ju Hong Lee, MD, PhD, Chonbuk National University Hospital; Principal Investigator: Ui Seong Choi, MD, PhD, Chungbuk National University Hospital; Principal Investigator: Chung Hyeok Choi, MD, PhD, Hanyang University

Publications and helpful links

General Publications

• Kim MK, Ha CW, In Y, Cho SD, Choi ES, Ha JK, Lee JH, Yoo JD, Bin SI, Choi CH, Kyung HS, Lee MC. A Multicenter, Double-Blind, Phase III Clinical Trial to Evaluate the Efficacy and Safety of a Cell and Gene Therapy in Knee Osteoarthritis Patients. Hum Gene Ther Clin Dev. 2018 Mar;29(1):48-59. doi: 10.1089/humc.2017.249.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): August 1, 2015

Study Registration Dates

• First Submitted: February 17, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (ESTIMATE): February 26, 2014

Study Record Updates

• Last Update Posted (ACTUAL): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 14, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: chondrocyte cells, Osteoarthritis, gene therapy
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: KS-TGC-01-3