Clinical trial NCT03383471: The Efficacy and Safety of Invossa K Injection in Patients Diagnosed With Knee Osteoarthritis
Official title: A Multicenter, Randomized, Placebo Controlled, Double-blind, Parallel, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Invossa K Injection in Patients Diagnosed as Knee Osteoarthritis With Kellgren & Lawrence Grade 2
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Osteoarthritis
Keywords: chondrocyte cells
osteoarthritis
gene therapy
Lead sponsor: Kolon Life Science
Sponsor class: INDUSTRY
First posted: 2017-12-26
Enrollment: 146
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 evaluate the efficacy and safety of intraarticular Invossa K Injection patients diagnosed with Kellgren \& Lawrence grade 2 knee osteoarthritis.


Eligibility criteria: Inclusion Criteria:

1. Male or female aged 19 and older
2. Patients with IKDC Subjective Knee Evaluation of ≤ 60 of the target knee.
3. Patients with a score of ≥ 40 on the 100 mm pain VAS of the target knee.
4. Patients with grade 2 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence
5. BMI should fall between 18.5 and 30
6. Patients who satisfies the clinical/radiational criteria by the American College of Rheumatology guidelines, and applies to one of the following.

   * Age \> 50 years old
   * Morning stiffness \< 30 minutes
   * Crepitus and Osteophytes
7. With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms
8. Patients with persistent symptoms in spite of conservative therapy for more than 3 months : Improvement of 100 mm VAS are less than 10 mm after 3 months
9. Healthy, with no major findings from the physical examination, hematology, serum chemistry, and urine tests, and no significant medical history
10. Agreed to use an effective contraceptive method during the study period
11. Voluntarily agreed to participate in this study, and signed the informed consent form

Exclusion Criteria:

1. Patients who had been administered with drugs such as oriental medicine, glucosamine and chondroitin within 14 days of baseline visit (But, possible to include after 14 days of wash-out period)
2. Patients taking steroidal anti-inflammatory medications within 14 days of baseline visit (But, possible to include after 14 days of wash-out period)
3. Patients with severe pain in other areas that could effect the diagnosis of the symptoms
4. Patients over Grade 3 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence
5. History of surgery like arthroendoscopy within the past 6 months on the target knee
6. Patients who had been administered with immunosuppressants, including antirheumatic drugs (including methotrexate or antimetabolite), within the past 3 months
7. History of injection within the past 3 months on the target knee
8. Pregnant or breastfeeding female
9. With another joint disease apart from degenerative arthritis
10. Patients with hepatitis including carrier
11. Patients with HIV and an infectious disease which is clinically uncontrolled
12. Patients who have any of the following clinically significant diseases or have a medical history within 6 months :

    * Clinically significant heart diseases which are considered by the investigator
    * Uncontrolled hypertension : if the systolic blood pressure exceeds 160 mmHg or diastolic blood pressure exceeds 100 mmHg in a sitting position
    * Kidney disease
    * Liver disease
    * Endocrine disease
    * Uncontrolled diabetes mellitus : HbA1c ≥ 9%
    * Paget's disease, ochronosis, acromegaly, hemochromatosis, Wilson's disease
    * Genetic diseases (hyperkinesia, collagen gene abnormality)
13. Medical history of past or current malignant tumor
14. Patients with a history of anaphylactic reactions
15. Patients with a history of hypersensitivity reactions to the components of this drug, including dimethylsulfoxide, mannitol, dextran 40 or bovine proteins
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 INVOSSA K inj.
18. Considered inappropriate by the investigator for participation in this study

Primary outcomes:
measure: IKDC (International knee documentation committee) Subjective Knee Evaluation
timeFrame: Week 0 and 52
measure: 100 mm VAS (Visual analogue scale)
timeFrame: Week 0 and 52
Secondary outcomes:
measure: WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index) score
timeFrame: Week 0, 26, 39 and 52
measure: IKDC Subjective Knee Evaluation
timeFrame: Week 0, 26 and 39
measure: 100 mm VAS
timeFrame: Week 0, 26 and 39
measure: OMERACT-OARSI (Outcome measures in rheumatology-Osteoarthritis research society international) response rate
timeFrame: Week 26, 39 and 52
measure: MRI scan
timeFrame: Week 0, and 52
measure: Joint Space Width
timeFrame: Week 0, and 52
measure: Biomarker (CTX-I) in blood
timeFrame: Week 0, 26, and 52
measure: Biomarker (CTX-II) in urine
timeFrame: Week 0, 26, and 52
measure: Rescue Medication (Dosage)
timeFrame: Week 0, 4, 12, 26, 39, and 52
measure: Rescue Medication (Frequency)
timeFrame: Week 0, 4, 12, 26, 39, and 52
measure: Drop-out rate
timeFrame: Week 0, 4, 12, 26, 39, and 52
measure: Reason of drop-out
timeFrame: Week 0, 4, 12, 26, 39, and 52
Other outcomes:
Locations:
city: Ansan
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University School of Medicine
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University School of Medicine
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: College of Medicine, Hanyang University
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: School of Medicine, Kyung Hee University
city: Seoul
country: Korea, Republic of
facility: Seoul National University Borame Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea College of Medicine
city: Seoul
country: Korea, Republic of
facility: Yonsei University School of Medicine
city: Suwon
country: Korea, Republic of
facility: Ajou University School of Medicine
Study officials:
affiliation: Department of Orthopedic Surgery, Seoul National University Hospital
name: Myung-Chul Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: