The Efficacy and Safety of Invossa K Injection in Patients Diagnosed With Knee Osteoarthritis

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Osteoarthritis

Intervention / Treatment
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* Biological: Invossa K Inj.
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 19 and older Patients with IKDC Subjective Knee Evaluation of ≤ 60 of the target knee. Patients with a score of ≥ 40 on the 100 mm pain VAS of the target knee. Patients with grade 2 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence BMI should fall between 18.5 and 30 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 With major lesions concentrated in one section of the knee, and with the major lesions considered the main cause of the clinical symptoms 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 Healthy, with no major findings from the physical examination, hematology, serum chemistry, and urine tests, and no significant medical history Agreed to use an effective contraceptive method during the study period Voluntarily agreed to participate in this study, and signed the informed consent form Exclusion Criteria: 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) Patients taking steroidal anti-inflammatory medications within 14 days of baseline visit (But, possible to include after 14 days of wash-out period) Patients with severe pain in other areas that could effect the diagnosis of the symptoms Patients over Grade 3 osteoarthritis as determined by the radiographic criteria of Kellgren and Lawrence History of surgery like arthroendoscopy within the past 6 months on the target knee Patients who had been administered with immunosuppressants, including antirheumatic drugs (including methotrexate or antimetabolite), within the past 3 months History of injection within the past 3 months on the target knee Pregnant or breastfeeding female With another joint disease apart from degenerative arthritis Patients with hepatitis including carrier Patients with HIV and an infectious disease which is clinically uncontrolled 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) Medical history of past or current malignant tumor Patients with a history of anaphylactic reactions Patients with a history of hypersensitivity reactions to the components of this drug, including dimethylsulfoxide, mannitol, dextran 40 or bovine proteins Participated in another clinical trial (using the investigational drug or a medical device) within 30 days before enrollment in this study Patients who administered the INVOSSA K inj. Considered inappropriate by the investigator for participation in this study

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Invossa K Inj.<br>Invossa K Inj. | Biological: Invossa K Inj.<br>* Invossa K Inj.<br>|
| Placebo Comparator: Placebo<br>Placebo control | Drug: Placebo<br>* Placebo control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IKDC (International knee documentation committee) Subjective Knee Evaluation | Changes in IKDC Subjective Knee Evaluation (score) | Week 0 and 52 | 
| 100 mm VAS (Visual analogue scale) | Changes in 100 mm VAS | Week 0 and 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index) score | Changes in WOMAC (score) | Week 0, 26, 39 and 52 | 
| IKDC Subjective Knee Evaluation | Changes in IKDC Subjective Knee Evaluation (score) | Week 0, 26 and 39 | 
| 100 mm VAS | Changes in 100 mm VAS | Week 0, 26 and 39 | 
| OMERACT-OARSI (Outcome measures in rheumatology-Osteoarthritis research society international) response rate | OMERACT-OARSI response rate after administration (%) | Week 26, 39 and 52 | 
| MRI scan | Changes in MRI scan | Week 0, and 52 | 
| Joint Space Width | Changes in Joint Space Width (mm) | Week 0, and 52 | 
| Biomarker (CTX-I) in blood | Levels of CTX-I in blood (ng/ml) | Week 0, 26, and 52 | 
| Biomarker (CTX-II) in urine | Levels of CTX-II in urine (ng/ml) | Week 0, 26, and 52 | 
| Rescue Medication (Dosage) | Dosage of Rescue Medication (mg) | Week 0, 4, 12, 26, 39, and 52 | 
| Rescue Medication (Frequency) | Frequency of Rescue Medication (number) | Week 0, 4, 12, 26, 39, and 52 | 
| Drop-out rate | Drop-out rate (%) | Week 0, 4, 12, 26, 39, and 52 | 
| Reason of drop-out | Reason of drop-out is recorded in CRF (Case Report Form), when the patient is dropped-out according to drop-out criteria (e.g. Withdraw a consent, Patients who can not continuously participate in study due to adverse events, Impossible to follow-up of the patient. etc.). | Week 0, 4, 12, 26, 39, and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chondrocyte cells, osteoarthritis, gene therapy