Clinical trial NCT02072070: Efficacy and Safety Study of TissueGene-C to Degenerative Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Degenerative Arthritis
Keywords: chondrocyte cells, Osteoarthritis, gene therapy
Lead sponsor: Kolon Life Science
Sponsor class: INDUSTRY
First posted: 2014-02-26
Enrollment: 163
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in IKDC scores
timeFrame: Week 0 and 52
measure: Changes in 100 mm VAS scores
timeFrame: Week 0 and 52
Secondary outcomes:
measure: Changes in WOMAC scores
timeFrame: Wekk 0, 26, 39 and 52
measure: Changes in KOOS scores
timeFrame: Week 0, 26, 39 and 52
measure: Changes in MRI scan
timeFrame: Week 0, 26 and 52
measure: Changes in Joint Space Width by an independent radiographic reviewer.
timeFrame: Week 0, 26 and 52
measure: Level of Biomarkers in blood and urine.
timeFrame: Week 0, 26, 39 and 52
measure: Proportion of Patients Use of Rescue Medication.
timeFrame: Week 4, 12, 26, 39 and 52
measure: Changes in IKDC scores
timeFrame: Week 0, 26 and 39
measure: Changes in 100 mm VAS scores
timeFrame: Week 0, 26 and 39
Other outcomes:
Locations:
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National Univ. Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Inje University Seoul Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
Study officials:
affiliation: Inje University
name: Jin Gu Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kyungpook National University Hospital
name: Su Hee Kyung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Samsung Medical Center
name: Chul Won Ha, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital
name: Myung Chul Lee, MD, PhD
role: STUDY_CHAIR
affiliation: The Catholic University of Korea Seoul ST. Mary's Hospita
name: Yong In, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Asan Medical Center
name: Seong Il Bin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ulsan University Hospital
name: Seong Do Cho, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ewha Womans University Mokdong
name: Jae Doo Yoo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inha University Hospital
name: Myung Gu Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chonbuk National University Hospital
name: Ju Hong Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chungbuk National University Hospital
name: Ui Seong Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hanyang University
name: Chung Hyeok Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.